How to use GIP / GLP1 coagonists for therapeutic purposes

Abstract

The present invention provides a pharmaceutical composition for use in treating atherosclerosis. [Solution] A pharmaceutical composition is provided for use in treating atherosclerosis, comprising tilzepatide or a pharmaceutically acceptable salt thereof, characterized in that at least one escalating dose is administered once a week for at least two weeks, and thereafter at least one maintenance dose is administered once a week for at least two weeks, wherein the escalating dose is selected from the group consisting of 2.5 mg, 7.5 mg, and 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of 5.0 mg, 10.0 mg, and 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

Description

Technical Field

[0001] The present invention provides methods of using a novel dosage of a glucose-dependent insulinotropic polypeptide (GIP) / glucagon-like peptide-1 (GLP1) dual agonist peptide, tirzepatide, or a pharmaceutically acceptable salt thereof for treating type 2 diabetes (T2D). The present invention also provides methods of using a novel dosing schedule of a GIP / GLP1 dual agonist peptide, tirzepatide, or a pharmaceutically acceptable salt thereof for treating type 2 diabetes. Further, the present invention provides a novel medical use of tirzepatide, or a pharmaceutically acceptable salt thereof. More specifically, the present invention provides methods for treating a condition selected from the group consisting of chronic kidney disease, atherosclerosis, non-alcoholic fatty liver disease ("NAFLD"), and non-alcoholic steatohepatitis ("NASH"). In a further embodiment, the present invention provides methods for treating diabetes in a particular patient.

[0002] Diabetes is a chronic disease characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. In T2D, the combined effects of impaired insulin secretion and insulin resistance are associated with elevated blood glucose levels.

[0003] US9474780 describes compositions comprising a GIP / GLP1 coagonist generally administered by a parenteral route and discloses a broad dosage range of up to about 30 mg per person per week. US9474780 discloses the use of a GIP / GLP1 coagonist for treating diabetes, obesity, and other conditions. US9474780 describes and claims tirzepatide.

[0004] It is well known that GLP-1 therapy is associated with nausea, vomiting, and / or diarrhea. For example, one study reported that all GLP-1 receptor agonist regimens significantly increased the incidence of gastrointestinal adverse events. Diabetes Technol Ther. 2015 Jan;17(1):35-42. Additionally, previous clinical trials of GIP / GLP1 coagonist compounds have shown that tolerability at high doses is limited by gastrointestinal adverse events.Schmitt, C. et al. “Pharmacodynamics, pharmacokinetics and safety of multiple ascending doses of the novel dual glucose-dependent insulinotropic polypeptide / glucagon-like peptide-1 agonist RG7697 in people with type 2 diabetes mellitus.”Diabetes Obes.Metab.2017;19:1436-1445.Portron, A.et al. “Pharmacodynamics,Pharmacokinetics,Safety, and Tolerability of the Novel Dual GIP / GLP-1 Agonist(RG7697)after Single Subcutaneous Administration in Healthy Subjects.”2390-PUB,A624,ADA-2017;Portron,A.et al. polypeptide / glucagon-like peptide-1 agonist RG7697 after single subcutaneous administration in healthy subjects.”Diabetes Obes. Metab. 2017;19:14446-1453. Dose limitations related to gastrointestinal adverse events may prevent administration of the desired effective dose, impair patient compliance with treatment, and limit the effectiveness of the treatment plan.

[0005] Novel doses of tirzepatide are needed to provide desired glycemic control, for example, as demonstrated by further reductions in HbA1c and / or weight loss, while maintaining an acceptable safety and adverse event profile. Novel dosing regimens of tirzepatide are also needed to provide desired glycemic control, for example, as demonstrated by further reductions in HbA1c and / or weight loss, while maintaining an acceptable safety and adverse event profile. In addition, there is a need for GIP / GLP1 dual agonist treatment options for selected conditions from chronic kidney disease, atherosclerosis, NAFLD, and NASH. Furthermore, there is a desire for treatments that cure diabetes by preventing it, reducing its severity, or inducing remission. There is a desire for treatments that reduce or slow the progression of diabetes. [Overview of the Initiative]

[0006] The present invention provides a novel tylzepatide dosing regimen for use in the aforementioned therapies, comprising a maintenance dose selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg. In another embodiment, the present invention provides a novel dosing regimen comprising an escalating dose (i.e., a dose lower than the desired maintenance dose) and a maintenance dose. In another embodiment, the present invention provides a novel dosing regimen comprising one or more escalating doses and one or more maintenance doses. The present invention provides a novel dosing regimen comprising administering at least one escalating dose approximately once a week for a minimum of approximately four weeks, followed by at least one maintenance dose approximately once a week for a minimum of approximately four weeks. In certain embodiments, the dose may be administered for approximately four weeks. In certain embodiments, the dose may be administered for more than approximately four weeks, as determined by the nurse, patient, and / or healthcare provider. For example, the maintenance dose may be administered for more than approximately four weeks. In certain embodiments of the present invention, if additional glycemic control is required, with or without the intervening escalating dose, the maintenance dose may be increased to the next highest maintenance dose of the present invention. For example, in one dosing regimen according to the present invention, the escalating dose is approximately 2.5 mg and the maintenance dose is approximately 5.0 mg. In another dosing regimen according to the present invention, the two escalating doses are approximately 2.5 mg and approximately 7.5 mg, and the maintenance doses are approximately 5.0 mg and 10.0 mg. In another aspect of the present invention, the escalating doses are approximately 2.5 mg, approximately 7.5 mg and approximately 12.5 mg, and the maintenance doses are approximately 5.0 mg, approximately 10.0 mg and approximately 15.0 mg. The escalating doses include approximately 2.5 mg, approximately 7.5 mg and approximately 12.5 mg. The maintenance doses include approximately 5.0 mg, approximately 10.0 mg and approximately 15.0 mg. The escalating dose of approximately 2.5 mg may be the initial dose or starting dose in the dosing regimen provided herein. As used herein, the terms “escalation” or “escalation dose(s)” mean the titration or titration dose as described herein.

[0007] Accordingly, the present invention provides a method for treating type 2 diabetes in a patient requiring treatment for type 2 diabetes, comprising administering an escalating dose approximately once a week for at least about four weeks, and then administering a maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an incremental increase of 2.5 mg compared to the escalating dose. Accordingly, one embodiment of the present invention provides a method for treating type 2 diabetes, wherein the escalating dose administered approximately once a week for at least about four weeks is about 2.5 mg, and the maintenance dose administered approximately once a week for at least about four weeks is about 5.0 mg. A further embodiment of the present invention is a method in which an escalating dose of about 7.5 mg is administered approximately once a week for at least about 4 weeks, and a maintenance dose of about 10.0 mg is administered approximately once a week for at least about 4 weeks. A further embodiment of the present invention is a method in which an escalating dose of about 12.5 mg is administered approximately once a week for at least about 4 weeks, and a maintenance dose of about 15.0 mg is administered approximately once a week for at least about 4 weeks. A further embodiment of the present invention is in which a first maintenance dose is administered for at least about 4 weeks, followed by a second escalating dose administered approximately once a week for at least about 4 weeks, and then a second maintenance dose administered approximately once a week for at least about 4 weeks. Thus, one such method includes escalating doses of about 2.5 mg and about 7.5 mg and maintenance doses of about 5.0 mg and about 10.0 mg. Another embodiment of the present invention involves administering a second maintenance dose for at least about four weeks, followed by a third escalating dose approximately once a week for at least about four weeks, and then a third maintenance dose approximately once a week for at least four weeks. Thus, one such method includes escalating doses of about 2.5 mg, about 7.5 mg, and about 12.5 mg, as well as maintenance doses of about 5.0 mg, about 10.0 mg, and about 15.0 mg.

[0008] As described above, in certain embodiments of the present invention, the maintenance dose may be increased to a subsequent maintenance dose if additional blood glucose control is required, with or without the intervention of an escalating dose. Accordingly, the present invention further provides a method for treating type 2 diabetes in a patient requiring treatment for type 2 diabetes, comprising administering an escalating dose of about 2.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least about 4 weeks; then administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least about 4 weeks; optionally administering a second maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least about 4 weeks; and optionally administering a third maintenance dose of about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least about 4 weeks.

[0009] In another aspect, the present invention relates to a method for treating type 2 diabetes in patients who require treatment for type 2 diabetes, a) Administer approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable dose thereof, to the patient approximately once a week for at least approximately 4 weeks. b) Increase the dose to approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and administer it to the patient approximately once a week for at least approximately 4 weeks. c) Increase the dose to approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and administer it to the patient approximately once a week for at least approximately 4 weeks. d) Increase the dose to approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and administer it to the patient approximately once a week for at least approximately 4 weeks. e) Increase the dose to approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and administer it to the patient approximately once a week for at least approximately 4 weeks. f) The present invention provides a method comprising increasing the dose to approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and administering it to the patient approximately once a week for at least approximately 4 weeks.

[0010] In one aspect, the present invention relates to a method for treating type 2 diabetes in patients who require treatment for type 2 diabetes, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0011] In another embodiment, the present invention provides a method for treating type 2 diabetes in a patient requiring treatment for type 2 diabetes, comprising administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about 4 weeks.

[0012] Another embodiment is a method for treating type 2 diabetes in a patient who requires treatment for type 2 diabetes, a) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0013] Another embodiment is a method for treating type 2 diabetes in a patient who requires treatment for type 2 diabetes, a) Administer the patient approximately 7.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0014] In another aspect, the present invention provides a method for treating type 2 diabetes in a patient requiring treatment for type 2 diabetes, comprising administering a maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about 4 weeks.

[0015] Another embodiment is a method for treating type 2 diabetes in a patient who requires treatment for type 2 diabetes, a) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0016] Another embodiment is a method for treating type 2 diabetes in a patient who requires treatment for type 2 diabetes, a) Administer the patient approximately 12.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0017] In another aspect, the present invention provides a method for treating type 2 diabetes in a patient requiring treatment for type 2 diabetes, comprising administering a maintenance dose of about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about 4 weeks.

[0018] In another aspect, the present invention relates to a method for treating type 2 diabetes in patients who require treatment for type 2 diabetes, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administering to the patient a maintenance dose of approximately 5.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately weekly for at least approximately 4 weeks, and then c) Administering to the patient a titrating dose of approximately 7.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately weekly for at least approximately 4 weeks, and then d) Administering to the patient a maintenance dose of approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately weekly for at least approximately 4 weeks, to provide a method.

[0019] In another aspect, the present invention includes the method described in the previous paragraph, which does not include administering a titrating dose of 7.5 mg.

[0020] In another aspect, the present invention is a method for treating type 2 diabetes in a patient who requires treatment for type 2 diabetes, g) Administering to the patient a titrating dose of approximately 2.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately weekly for at least approximately 4 weeks, and then h) Administering to the patient a maintenance dose of approximately 5.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately weekly for at least approximately 4 weeks, and then i) Administering to the patient a titrating dose of approximately 7.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately weekly for at least approximately 4 weeks, and then j) Administering to the patient a maintenance dose of approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately weekly for at least approximately 4 weeks, and then k) Administering to the patient a titrating dose of approximately 12.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately weekly for at least approximately 4 weeks, and then l) Administering to the patient a maintenance dose of approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately weekly for at least approximately 4 weeks, to provide a method.

[0021] In another aspect, the present invention includes the method described in the previous paragraph, but this does not include administering a escalating dose of 7.5 mg. In another aspect, the present invention includes the method described in the previous paragraph, but this does not include administering a escalating dose of 12.5 mg. In another aspect, the present invention includes the method described in the previous paragraph, but this does not include administering escalating doses of 7.5 mg and 12.5 mg.

[0022] Furthermore, the present invention provides a method for improving blood glucose control in patients requiring improved blood glucose control, comprising administering at least one escalating dose approximately once a week for at least about four weeks, and then at least one maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg compared to the escalating dose. Accordingly, one embodiment of the present invention provides a method for improving blood glucose control, wherein the escalating dose administered approximately once a week for at least about four weeks is approximately 2.5 mg, and the maintenance dose administered approximately once a week for at least about four weeks is approximately 5.0 mg. A further embodiment of the present invention is a method in which an escalating dose of about 7.5 mg is administered approximately once a week for at least about 4 weeks, and a maintenance dose of about 10.0 mg is administered approximately once a week for at least about 4 weeks. A further embodiment of the present invention is a method in which an escalating dose of about 12.5 mg is administered approximately once a week for at least about 4 weeks, and a maintenance dose of about 15.0 mg is administered approximately once a week for at least about 4 weeks. A further embodiment of the present invention is in which a first maintenance dose is administered for at least about 4 weeks, followed by a second escalating dose administered approximately once a week for at least about 4 weeks, and then a second maintenance dose is administered approximately once a week for at least about 4 weeks. Thus, one such method includes escalating doses of about 2.5 mg and about 7.5 mg and maintenance doses of about 5.0 mg and about 10.0 mg. A further embodiment of the present invention involves administering a second maintenance dose for at least about four weeks, followed by a third escalating dose approximately once a week for at least about four weeks, and then a third maintenance dose approximately once a week for at least four weeks. Thus, one such method includes escalating doses of about 2.5 mg, about 7.5 mg, and about 12.5 mg, as well as maintenance doses of about 5.0 mg, about 10.0 mg, and about 15.0 mg.

[0023] As described above, in certain embodiments of the present invention, the maintenance dose may be increased to a subsequent maintenance dose if additional blood glucose control is required, with or without the presence of an intervening dose escalation. Accordingly, the present invention further provides a method for improving blood glucose control in a patient requiring improved blood glucose control, comprising administering an escalating dose of about 2.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least about 4 weeks; then administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least about 4 weeks; optionally administering a second maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least about 4 weeks; and optionally administering a third maintenance dose of about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least about 4 weeks.

[0024] Furthermore, the present invention relates to a method for improving blood glucose control in patients who require improvement in blood glucose control, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0025] In another aspect, the present invention provides a method for improving blood glucose control in a patient requiring improvement in blood glucose control, comprising administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0026] Another embodiment is a method for improving blood glucose control in a patient who requires improved blood glucose control, a) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0027] Another embodiment is a method for improving blood glucose control in a patient who requires improved blood glucose control, a) Administer the patient approximately 7.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0028] In another embodiment, the present invention provides a method for improving blood glucose control in a patient requiring improvement in blood glucose control, comprising administering a maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0029] Another embodiment is a method for improving blood glucose control in a patient who requires improved blood glucose control, a) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0030] Another embodiment is a method for improving blood glucose control in a patient who requires improved blood glucose control, a) Administer the patient approximately 12.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0031] In another aspect, the present invention provides a method for improving blood glucose control in a patient requiring improvement in blood glucose control, comprising administering a maintenance dose of about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0032] In another aspect, the present invention relates to a method for improving blood glucose control in patients who require improvement in blood glucose control, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) A method is provided comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks, and thereafter. In another embodiment, the present invention includes the method described in the previous paragraph, but does not include administering a gradually increasing dose of 7.5 mg.

[0033] In another aspect, the present invention relates to a method for improving blood glucose control in patients who require improvement in blood glucose control, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter e) Administer the patient approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter f) A method is provided comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0034] In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering an increasing dose of 7.5 mg. In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering an increasing dose of 12.5 mg. In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering increasing doses of 7.5 mg and 12.5 mg.

[0035] In a further embodiment, a method for treating type 2 diabetes in a patient requiring treatment for type 2 diabetes, comprising administering tilzepatide or a pharmaceutically acceptable salt thereof in a tilzepatide administration plan comprising an initiation phase, at least one escalation phase, and a maintenance phase, wherein the initiation phase comprises administering 2.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least about 2 to 4 weeks, the escalation phase comprises administering doses increasing by about 2.5 mg per week for at least about 2 to 4 weeks from the dose of the initiation phase or the dose of the previous escalation phase, with each escalation phase increasing by about 2.5 mg, the escalation dose increasing by 2.5 mg between each escalation phase until a maintenance phase is reached, and the maintenance phase is administered approximately once a week in doses selected from the group consisting of about 5 mg, about 10 mg, and about 15 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

[0036] Furthermore, the present invention provides a method for improving weight management in patients requiring improved weight management, comprising administering an escalating dose approximately once a week for at least about four weeks, and then administering a maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg compared to the escalating dose. Accordingly, one embodiment of the present invention provides a method for improving weight management, wherein the escalating dose administered approximately once a week for at least about four weeks is approximately 2.5 mg, and the maintenance dose administered approximately once a week for at least about four weeks is approximately 5.0 mg. A further embodiment of the present invention is a method in which an escalating dose of about 7.5 mg is administered approximately once a week for at least about 4 weeks, and a maintenance dose of about 10.0 mg is administered approximately once a week for at least about 4 weeks. A further embodiment of the present invention is a method in which an escalating dose of about 12.5 mg is administered approximately once a week for at least about 4 weeks, and a maintenance dose of about 15.0 mg is administered approximately once a week for at least about 4 weeks. A further embodiment of the present invention is in which a first maintenance dose is administered for at least about 4 weeks, followed by a second escalating dose administered approximately once a week for at least about 4 weeks, and then a second maintenance dose is administered approximately once a week for at least about 4 weeks. Thus, one such method includes escalating doses of about 2.5 mg and about 7.5 mg and maintenance doses of about 5.0 mg and about 10.0 mg. Another embodiment of the present invention involves administering a second maintenance dose for at least about four weeks, followed by a third escalating dose approximately once a week for at least about four weeks, and then a third maintenance dose approximately once a week for at least four weeks. Thus, one such method includes escalating doses of about 2.5 mg, about 7.5 mg, and about 12.5 mg, as well as maintenance doses of about 5.0 mg, about 10.0 mg, and about 15.0 mg.

[0037] As described above, in certain embodiments of the present invention, the maintenance dose may be increased to a subsequent maintenance dose if additional blood glucose control is required, with or without the intervention of an escalating dose. Accordingly, the present invention further provides a method for improving weight management in a patient requiring improved weight management, comprising administering an escalating dose of about 2.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least about 4 weeks; then administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least about 4 weeks; optionally administering a second maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least about 4 weeks; and optionally administering a third maintenance dose of about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least about 4 weeks.

[0038] In yet another aspect, the present invention relates to a method for improving weight management in patients who require improved weight management, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0039] In another embodiment, the present invention provides a method for improving the weight management of a patient requiring improved weight management, comprising administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0040] Another embodiment is a method for improving weight management in patients who require improved weight management, a) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0041] Another embodiment is a method for improving weight management in patients who require improved weight management, a) Administer the patient approximately 7.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0042] In another embodiment, the present invention provides a method for improving the weight management of a patient requiring improved weight management, comprising administering a maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0043] Another embodiment is a method for improving weight management in patients who require improved weight management, a) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0044] Another embodiment is a method for improving weight management in patients who require improved weight management, a) Administer the patient approximately 12.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks. b) A method is provided comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0045] In another embodiment, the present invention provides a method for improving the weight management of a patient requiring improved weight management, comprising administering a maintenance dose of about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0046] In another embodiment, the present invention relates to a method for improving weight management in patients who require improved weight management, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) A method is provided comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0047] In another embodiment, the present invention includes the method described in the previous paragraph, but does not include administering a gradually increasing dose of 7.5 mg.

[0048] In another embodiment, the present invention relates to a method for improving weight management in patients who require improved weight management, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter e) Administer the patient approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter f) A method is provided comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0049] In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering an increasing dose of 7.5 mg. In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering an increasing dose of 12.5 mg. In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering increasing doses of 7.5 mg and 12.5 mg.

[0050] Furthermore, the present invention provides a method for treating chronic kidney disease in patients requiring treatment for chronic kidney disease, comprising administering an escalating dose approximately once a week for at least about four weeks, and then administering a maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg compared to the escalating dose. In one embodiment of the method for treating chronic kidney disease, the escalating dose administered approximately once a week for at least about four weeks is approximately 2.5 mg, and the maintenance dose administered approximately once a week for at least about four weeks is approximately 5.0 mg. A further embodiment of the present invention is a method in which the escalating dose is approximately 7.5 mg administered approximately once a week for at least approximately 4 weeks, and the maintenance dose is approximately 10.0 mg administered approximately once a week for at least approximately 4 weeks. A further embodiment of the present invention is a method in which the escalating dose is approximately 12.5 mg administered approximately once a week for at least approximately 4 weeks, and the maintenance dose is approximately 15.0 mg administered approximately once a week for at least approximately 4 weeks. A further embodiment of the present invention is a method in which the escalating doses are approximately 2.5 mg and approximately 7.5 mg administered approximately once a week for at least approximately 4 weeks, and the maintenance doses are approximately 5.0 mg and approximately 10.0 mg administered approximately once a week for at least approximately 4 weeks. Further embodiments of the present invention include escalating doses of approximately 2.5 mg, 5.0 mg, and 7.5 mg administered approximately once a week for at least about 4 weeks, and maintenance doses of approximately 5.0 mg, 10.0 mg, and 15.0 mg administered approximately once a week for at least about 4 weeks.

[0051] Therefore, the present invention relates to a method for treating chronic kidney disease in patients who require treatment for chronic kidney disease, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 5.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0052] In another aspect, the present invention provides a method for treating chronic kidney disease in a patient requiring treatment for chronic kidney disease, comprising administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0053] In another embodiment, a method for treating chronic kidney disease in a patient requiring treatment for chronic kidney disease, a) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 10.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0054] In another embodiment, a method for treating chronic kidney disease in a patient requiring treatment for chronic kidney disease, a) Administer the patient approximately 7.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 10.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0055] In another aspect, the present invention provides a method for treating chronic kidney disease in a patient requiring treatment for chronic kidney disease, comprising administering a maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0056] In another embodiment, a method for treating chronic kidney disease in a patient requiring treatment for chronic kidney disease, a) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 15.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0057] In another embodiment, a method for treating chronic kidney disease in a patient requiring treatment for chronic kidney disease, a) Administer the patient approximately 12.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 15.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0058] In another aspect, the present invention provides a method for treating chronic kidney disease in a patient requiring treatment for chronic kidney disease, comprising administering a maintenance dose of about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0059] In another aspect, the present invention relates to a method for treating chronic kidney disease in patients who require treatment for chronic kidney disease, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) A method is provided comprising administering to the patient approximately once a week for at least approximately four weeks an increasing dose of tilzepatide or a pharmaceutically acceptable salt thereof. d) A method is provided comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0060] In another embodiment, the present invention includes the method described in the previous paragraph, but does not include administering a gradually increasing dose of 7.5 mg.

[0061] In another aspect, the present invention relates to a method for treating chronic kidney disease in patients who require treatment for chronic kidney disease, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter e) Administer the patient approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter f) A method is provided comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0062] In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering an increasing dose of 7.5 mg. In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering an increasing dose of 12.5 mg. In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering increasing doses of 7.5 mg and 12.5 mg.

[0063] In a further embodiment, a method for treating chronic kidney disease in a patient requiring treatment for chronic kidney disease, comprising administering an escalating dose approximately once a week for at least about four weeks, and then administering a maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg compared to the escalating dose.

[0064] Furthermore, the present invention provides a method for treating atherosclerosis in patients requiring treatment for atherosclerosis, comprising administering an escalating dose approximately once a week for at least about four weeks, and then administering a maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg compared to the escalating dose. One embodiment of the method for treating atherosclerosis is an escalating dose administered approximately once a week for at least about four weeks being approximately 2.5 mg, and a maintenance dose administered approximately once a week for at least about four weeks being approximately 5.0 mg. A further embodiment of the present invention is a method in which the escalating dose is approximately 7.5 mg administered approximately once a week for at least approximately 4 weeks, and the maintenance dose is approximately 10.0 mg administered approximately once a week for at least approximately 4 weeks. A further embodiment of the present invention is a method in which the escalating dose is approximately 12.5 mg administered approximately once a week for at least approximately 4 weeks, and the maintenance dose is approximately 15.0 mg administered approximately once a week for at least approximately 4 weeks. A further embodiment of the present invention is a method in which the escalating doses are approximately 2.5 mg and approximately 7.5 mg administered approximately once a week for at least approximately 4 weeks, and the maintenance doses are approximately 5.0 mg and approximately 10.0 mg administered approximately once a week for at least approximately 4 weeks. Further embodiments of the present invention include escalating doses of approximately 2.5 mg, 5.0 mg, and 7.5 mg administered approximately once a week for at least about 4 weeks, and maintenance doses of approximately 5.0 mg, 10.0 mg, and 15.0 mg administered approximately once a week for at least about 4 weeks.

[0065] In a further embodiment, the present invention relates to a method for treating atherosclerosis in patients who require treatment for atherosclerosis, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 5.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0066] In another embodiment, the present invention provides a method for treating atherosclerosis in a patient requiring treatment for atherosclerosis, comprising administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about 4 weeks.

[0067] Another embodiment is a method for treating atherosclerosis in a patient who requires treatment for atherosclerosis, a) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 10.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0068] Another embodiment is a method for treating atherosclerosis in a patient who requires treatment for atherosclerosis, a) Administer the patient approximately 7.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 10.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0069] In another aspect, the present invention provides a method for treating atherosclerosis in a patient requiring treatment for atherosclerosis, comprising administering a maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0070] Another embodiment is a method for treating atherosclerosis in a patient who requires treatment for atherosclerosis, a) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 15.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0071] Another embodiment is a method for treating atherosclerosis in a patient who requires treatment for atherosclerosis, a) Administer the patient approximately 12.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 15.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0072] In another aspect, the present invention relates to a method for treating atherosclerosis in patients who require treatment for atherosclerosis, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) A method is provided comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0073] In another embodiment, the present invention includes the method described in the previous paragraph, but does not include administering a gradually increasing dose of 7.5 mg.

[0074] In another aspect, the present invention relates to a method for treating atherosclerosis in patients who require treatment for atherosclerosis, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter e) Administer the patient approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter f) A method is provided comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0075] In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering an increasing dose of 7.5 mg. In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering an increasing dose of 12.5 mg. In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering increasing doses of 7.5 mg and 12.5 mg.

[0076] The present invention also provides a method for treating NAFLD in patients requiring treatment for NAFLD, comprising administering an escalating dose approximately once a week for at least about four weeks, and then administering a maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg compared to the escalating dose. One embodiment of the method for treating NAFLD is an escalating dose administered approximately once a week for at least about four weeks being about 2.5 mg, and a maintenance dose administered approximately once a week for at least about four weeks being about 5.0 mg. A further embodiment of the present invention is a method in which the escalating dose is approximately 7.5 mg administered approximately once a week for at least approximately 4 weeks, and the maintenance dose is approximately 10.0 mg administered approximately once a week for at least approximately 4 weeks. A further embodiment of the present invention is a method in which the escalating dose is approximately 12.5 mg administered approximately once a week for at least approximately 4 weeks, and the maintenance dose is approximately 15.0 mg administered approximately once a week for at least approximately 4 weeks. A further embodiment of the present invention is a method in which the escalating doses are approximately 2.5 mg and approximately 7.5 mg administered approximately once a week for at least approximately 4 weeks, and the maintenance doses are approximately 5.0 mg and approximately 10.0 mg administered approximately once a week for at least approximately 4 weeks. Further embodiments of the present invention include escalating doses of approximately 2.5 mg, 5.0 mg, and 7.5 mg administered approximately once a week for at least about 4 weeks, and maintenance doses of approximately 5.0 mg, 10.0 mg, and 15.0 mg administered approximately once a week for at least about 4 weeks.

[0077] Therefore, the present invention relates to a method for treating NAFLD in patients who require treatment for NAFLD, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 15.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0078] In another aspect, the present invention provides a method for treating NAFLD in a patient requiring treatment for NAFLD, comprising administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0079] Another embodiment is a method for treating NAFLD in a patient who requires treatment for NAFLD, a) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 10.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0080] Another embodiment is a method for treating NAFLD in a patient who requires treatment for NAFLD, a) Administer the patient approximately 7.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 10.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0081] In another embodiment, the present invention provides a method for treating NAFLD in a patient requiring treatment for NAFLD, comprising administering a maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0082] Another embodiment is a method for treating NAFLD in a patient who requires treatment for NAFLD, a) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 15.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0083] Another embodiment is a method for treating NAFLD in a patient who requires treatment for NAFLD, a) Administer the patient approximately 12.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 15.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0084] In another embodiment, the present invention provides a method for treating NAFLD in a patient requiring treatment for NAFLD, comprising administering to the patient about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof about once a week for at least about 4 weeks.

[0085] In another aspect, the present invention relates to a method for treating NAFLD in patients who require treatment for NAFLD, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) A method is provided comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0086] In another embodiment, the present invention includes the method described in the previous paragraph, but does not include administering a gradually increasing dose of 7.5 mg.

[0087] In another aspect, the present invention relates to a method for treating NAFLD in patients who require treatment for NAFLD, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter e) Administer the patient approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter f) A method is provided comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0088] In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering an increasing dose of 7.5 mg. In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering an increasing dose of 12.5 mg. In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering increasing doses of 7.5 mg and 12.5 mg.

[0089] In one embodiment, a method for treating dyslipidemia in a patient requiring treatment for dyslipidemia comprises administering an escalating dose approximately once a week for at least about four weeks, followed by administering a maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg compared to the escalating dose.

[0090] The present invention also provides a method for treating NASH in patients requiring treatment for NASH, comprising administering an escalating dose approximately once a week for at least about four weeks, and then administering a maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an incremental increase of 2.5 mg compared to the escalating dose. One embodiment of the method for treating NASH is a escalating dose administered approximately once a week for at least about four weeks being about 2.5 mg, and a maintenance dose administered approximately once a week for at least about four weeks being about 5.0 mg. A further embodiment of the present invention is a method in which the escalating dose is approximately 7.5 mg administered approximately once a week for at least approximately 4 weeks, and the maintenance dose is approximately 10.0 mg administered approximately once a week for at least approximately 4 weeks. A further embodiment of the present invention is a method in which the escalating dose is approximately 12.5 mg administered approximately once a week for at least approximately 4 weeks, and the maintenance dose is approximately 15.0 mg administered approximately once a week for at least approximately 4 weeks. A further embodiment of the present invention is a method in which the escalating doses are approximately 2.5 mg and approximately 7.5 mg administered approximately once a week for at least approximately 4 weeks, and the maintenance doses are approximately 5.0 mg and approximately 10.0 mg administered approximately once a week for at least approximately 4 weeks. Further embodiments of the present invention include escalating doses of approximately 2.5 mg, 5.0 mg, and 7.5 mg administered approximately once a week for at least about 4 weeks, and maintenance doses of approximately 5.0 mg, 10.0 mg, and 15.0 mg administered approximately once a week for at least about 4 weeks.

[0091] Therefore, the present invention relates to a method for treating NASH in patients who require treatment for NASH, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 5.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0092] In another aspect, the present invention provides a method for treating NASH in a patient requiring treatment for NASH, comprising administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0093] Another embodiment is a method for treating NASH in a patient who requires treatment for NASH, a) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 10.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0094] Another embodiment is a method for treating NASH in a patient who requires treatment for NASH, a) Administer the patient approximately 7.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 10.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0095] In another embodiment, the present invention provides a method for treating NASH in a patient requiring treatment for NASH, comprising administering a maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0096] Another embodiment is a method for treating NASH in a patient who requires treatment for NASH, a) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 15.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0097] Another embodiment is a method for treating NASH in a patient who requires treatment for NASH, a) Administer the patient approximately 12.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 15.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0098] In another aspect, the present invention provides a method for treating NASH in a patient requiring treatment for NASH, comprising administering a maintenance dose of about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0099] In another aspect, the present invention relates to a method for treating NASH in patients who require treatment for NASH, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) A method is provided comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0100] In another embodiment, the present invention includes the method described in the previous paragraph, but does not include administering a gradually increasing dose of 7.5 mg.

[0101] In another aspect, the present invention relates to a method for treating NASH in patients who require treatment for NASH, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter e) Administer the patient approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter f) A method is provided comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0102] In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering an increasing dose of 7.5 mg. In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering an increasing dose of 12.5 mg. In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering increasing doses of 7.5 mg and 12.5 mg.

[0103] Furthermore, the present invention provides a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in patients who require the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, comprising administering an increasing dose approximately once a week for at least about four weeks, and then administering a maintenance dose approximately once a week for at least about four weeks, wherein the increasing dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the increasing dose is an increment of 2.5 mg compared to the increasing dose. One embodiment of a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes is a dose-escalating dose of about 2.5 mg administered approximately once a week for at least about 4 weeks, and a maintenance dose of about 5.0 mg administered approximately once a week for at least about 4 weeks. A further embodiment of the present invention is a method in which the dose-escalating dose is about 7.5 mg administered approximately once a week for at least about 4 weeks, and a maintenance dose of about 10.0 mg administered approximately once a week for at least about 4 weeks. A further embodiment of the present invention is a method in which the dose-escalating dose is about 12.5 mg administered approximately once a week for at least about 4 weeks, and a maintenance dose of about 15.0 mg administered approximately once a week for at least about 4 weeks. A further embodiment of the present invention is a method in which the dose-escalating doses are about 2.5 mg and about 7.5 mg administered approximately once a week for at least about 4 weeks, and a maintenance dose of about 5.0 mg and about 10.0 mg administered approximately once a week for at least about 4 weeks. Further embodiments of the present invention include escalating doses of approximately 2.5 mg, 5.0 mg, and 7.5 mg administered approximately once a week for at least about 4 weeks, and maintenance doses of approximately 5.0 mg, 10.0 mg, and 15.0 mg administered approximately once a week for at least about 4 weeks.

[0104] Therefore, the present invention relates to a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in patients who require the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 5.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0105] In another aspect, the present invention provides a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient who requires the treatment of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, comprising administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about 4 weeks.

[0106] Another embodiment is a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient who requires the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, a) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 10.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0107] Another embodiment is a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient who requires the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, a) Administer the patient approximately 7.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 10.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0108] In another aspect, the present invention provides a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient who requires the treatment of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, comprising administering a maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0109] Another embodiment is a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient who requires the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, a) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 15.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0110] Another embodiment is a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient who requires the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, a) Administer the patient approximately 12.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 15.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0111] In another aspect, the present invention provides a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient who requires the treatment of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, comprising administering a maintenance dose of about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0112] In another aspect, the present invention relates to a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient who requires the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) A method is provided comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0113] In another embodiment, the present invention includes the method described in the previous paragraph, but does not include administering a gradually increasing dose of 7.5 mg.

[0114] In another aspect, the present invention relates to a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient who requires the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter e) Administer the patient approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter f) A method is provided comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0115] In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering an increasing dose of 7.5 mg. In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering an increasing dose of 12.5 mg. In another embodiment, the present invention includes the method described in the preceding paragraph, but does not include administering increasing doses of 7.5 mg and 12.5 mg.

[0116] Furthermore, the present invention provides a drug for treating type 2 diabetes in patients requiring treatment for type 2 diabetes, comprising administering an escalating dose approximately once a week for at least about four weeks, and then administering a maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an incremental increase of 2.5 mg compared to the escalating dose, and provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of the drug.

[0117] The present invention is a drug for treating type 2 diabetes in patients who require treatment for type 2 diabetes, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0118] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating type 2 diabetes in a patient requiring treatment for type 2 diabetes, comprising administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about 4 weeks.

[0119] Another embodiment is a drug for treating type 2 diabetes in patients who require treatment for type 2 diabetes, a) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0120] Another embodiment is a drug for treating type 2 diabetes in patients who require treatment for type 2 diabetes, a) Administer the patient approximately 7.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0121] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating type 2 diabetes in a patient requiring treatment for type 2 diabetes, comprising administering a maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0122] Another embodiment is a drug for treating type 2 diabetes in patients who require treatment for type 2 diabetes, a) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0123] Another embodiment is a drug for treating type 2 diabetes in patients who require treatment for type 2 diabetes, a) Administer the patient approximately 12.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0124] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating type 2 diabetes in a patient requiring treatment for type 2 diabetes, comprising administering a maintenance dose of about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0125] In another aspect, the present invention relates to a drug for treating type 2 diabetes in patients who require treatment for type 2 diabetes, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0126] In another embodiment, the present invention includes the agent described in the previous paragraph, but does not include administering an increasing dose of 7.5 mg.

[0127] In another aspect, the present invention relates to a drug for treating type 2 diabetes in patients who require treatment for type 2 diabetes, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter e) Administer the patient approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter f) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0128] In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering an increasing dose of 7.5 mg. In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering an increasing dose of 12.5 mg. In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering increasing doses of 7.5 mg and 12.5 mg.

[0129] Furthermore, the present invention provides a drug for improving blood glucose control in patients requiring improved blood glucose control, comprising administering an escalating dose approximately once a week for at least about four weeks, and then administering a maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an incremental increase of 2.5 mg compared to the escalating dose, and provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of the drug.

[0130] Furthermore, the present invention relates to a drug that improves blood glucose control in patients who require improvement in blood glucose control, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0131] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for improving blood glucose control in a patient requiring improvement in blood glucose control, comprising administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0132] Another embodiment is a drug that improves blood glucose control in patients who require improved blood glucose control, a) Administer the patient approximately 5.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0133] Another embodiment is a drug that improves blood glucose control in patients who require improved blood glucose control, a) Administer the patient approximately 7.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0134] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for improving blood glucose control in a patient requiring improvement in blood glucose control, comprising administering a maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0135] Another embodiment is a drug that improves blood glucose control in patients who require improved blood glucose control, a) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0136] Another embodiment is a drug that improves blood glucose control in patients who require improved blood glucose control, a) Administer the patient approximately 12.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0137] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for improving blood glucose control in a patient requiring improvement in blood glucose control, comprising administering a maintenance dose of about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0138] In another aspect, the present invention relates to a drug for improving blood glucose control in patients who require improvement in blood glucose control, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0139] In another embodiment, the present invention includes the agent described in the previous paragraph, but does not include administering an increasing dose of 7.5 mg.

[0140] In another aspect, the present invention relates to a drug for improving blood glucose control in patients who require improvement in blood glucose control, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter e) Administer the patient approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter f) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0141] In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering an increasing dose of 7.5 mg. In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering an increasing dose of 12.5 mg. In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering increasing doses of 7.5 mg and 12.5 mg.

[0142] Furthermore, the present invention provides a drug for improving weight management in patients requiring improved weight management, comprising administering an escalating dose approximately once a week for at least about four weeks, and then administering a maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an incremental increase of 2.5 mg compared to the escalating dose, and provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of the drug.

[0143] In yet another embodiment, the present invention relates to a drug for improving weight management in patients who require improved weight management, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0144] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for improving weight management in a patient requiring improved weight management, comprising administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0145] Another embodiment is a drug that improves weight management in patients who require improved weight management, a) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0146] Another embodiment is a drug that improves weight management in patients who require improved weight management, a) Administer the patient approximately 7.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0147] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for improving weight management in a patient requiring improved weight management, comprising administering a maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0148] Another embodiment is a drug that improves weight management in patients who require improved weight management, a) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0149] Another embodiment is a drug that improves weight management in patients who require improved weight management, a) Administer the patient approximately 12.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0150] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for improving weight management in a patient requiring improved weight management, comprising administering a maintenance dose of about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0151] In another embodiment, the present invention relates to a drug for improving weight management in patients who require improved weight management, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0152] In another embodiment, the present invention includes the agent described in the previous paragraph, but does not include administering an increasing dose of 7.5 mg.

[0153] In another embodiment, the present invention relates to a drug for improving weight management in patients who require improved weight management, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter e) Administer the patient approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter f) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0154] In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering an increasing dose of 7.5 mg. In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering an increasing dose of 12.5 mg. In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering increasing doses of 7.5 mg and 12.5 mg.

[0155] Furthermore, the present invention provides a drug for treating chronic kidney disease in patients requiring treatment for chronic kidney disease, comprising administering an escalating dose approximately once a week for at least about four weeks, and then administering a maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an incremental increase of 2.5 mg compared to the escalating dose, thereby providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of the drug.

[0156] The present invention relates to a drug for treating chronic kidney disease in patients who require treatment for chronic kidney disease, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0157] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating chronic kidney disease in a patient requiring treatment for chronic kidney disease, comprising administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0158] Another embodiment is a drug for treating chronic kidney disease in patients who require treatment for chronic kidney disease, a) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0159] Another embodiment is a drug for treating chronic kidney disease in patients who require treatment for chronic kidney disease, a) Administer the patient approximately 7.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0160] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating chronic kidney disease in a patient requiring treatment for chronic kidney disease, comprising administering a maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0161] Another embodiment is a drug for treating chronic kidney disease in patients who require treatment for chronic kidney disease, a) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0162] Another embodiment is a drug for treating chronic kidney disease in patients who require treatment for chronic kidney disease, a) Administer the patient approximately 12.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0163] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating chronic kidney disease in a patient requiring treatment for chronic kidney disease, comprising administering a maintenance dose of about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0164] In another aspect, the present invention relates to a drug for treating chronic kidney disease in patients who require treatment for chronic kidney disease, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0165] In another embodiment, the present invention includes the agent described in the previous paragraph, but does not include administering an increasing dose of 7.5 mg.

[0166] In another aspect, the present invention relates to a drug for treating chronic kidney disease in patients who require treatment for chronic kidney disease, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter e) Administer the patient approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter f) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0167] In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering an increasing dose of 7.5 mg. In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering an increasing dose of 12.5 mg. In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering increasing doses of 7.5 mg and 12.5 mg.

[0168] In further embodiments, the present invention provides a drug for treating diabetic nephropathy in patients requiring treatment for diabetic nephropathy, comprising administering an escalating dose approximately once a week for a minimum of about four weeks, and then administering a maintenance dose approximately once a week for a minimum of about four weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an incremental increase of 2.5 mg compared to the escalating dose, thereby providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of the drug.

[0169] Furthermore, the present invention provides a drug for treating atherosclerosis in patients requiring treatment for atherosclerosis, comprising administering an escalating dose approximately once a week for at least about four weeks, and then administering a maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an incremental increase of 2.5 mg compared to the escalating dose, and provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of the drug.

[0170] Furthermore, the present invention relates to a drug for treating atherosclerosis in patients who require treatment for atherosclerosis, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0171] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating atherosclerosis in a patient requiring treatment for atherosclerosis, comprising administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about 4 weeks.

[0172] Another embodiment is a drug for treating atherosclerosis in patients who require treatment for atherosclerosis, a) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0173] Another embodiment is a drug for treating atherosclerosis in patients who require treatment for atherosclerosis, a) Administer the patient approximately 7.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0174] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating atherosclerosis in a patient requiring treatment for atherosclerosis, comprising administering a maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0175] Another embodiment is a drug for treating atherosclerosis in patients who require treatment for atherosclerosis, a) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0176] Another embodiment is a drug for treating atherosclerosis in patients who require treatment for atherosclerosis, a) Administer the patient approximately 12.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks. b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0177] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating atherosclerosis in a patient requiring treatment for atherosclerosis, comprising administering a maintenance dose of about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0178] In another aspect, the present invention relates to a drug for treating atherosclerosis in patients who require treatment for atherosclerosis, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0179] In another embodiment, the present invention includes the agent described in the previous paragraph, but does not include administering an increasing dose of 7.5 mg.

[0180] In another aspect, the present invention relates to a drug for treating atherosclerosis in patients who require treatment for atherosclerosis, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter e) Administer the patient approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter f) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0181] In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering an increasing dose of 7.5 mg. In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering an increasing dose of 12.5 mg. In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering increasing doses of 7.5 mg and 12.5 mg.

[0182] In one embodiment, a method for treating dyslipidemia in a patient requiring treatment for dyslipidemia comprises administering an escalating dose approximately once a week for at least about two weeks, and then administering a maintenance dose approximately once a week for at least about two weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

[0183] In one embodiment, a method for treating dyslipidemia in a patient requiring treatment for dyslipidemia, comprising administering at least one escalating dose approximately once a week for at least about four weeks, and then at least one maintenance dose approximately once a week for at least about four weeks thereafter, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

[0184] In one embodiment, there is a method for treating dyslipidemia, in which the gradually increasing dose is approximately 2.5 mg and the maintenance dose is approximately 5.0 mg.

[0185] In one embodiment, there is a method for treating dyslipidemia, wherein the gradually increasing dose is approximately 7.5 mg and the maintenance dose is approximately 10.0 mg.

[0186] In one embodiment, there is a method for treating dyslipidemia, wherein the gradually increasing dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

[0187] In one embodiment, a method for treating dyslipidemia further comprises an increasing dose of about 7.5 mg and a maintenance dose of about 10.0 mg.

[0188] In one embodiment, a method for treating dyslipidemia further comprising an escalating dose of about 12.5 mg and a maintenance dose of about 15.0 mg.

[0189] In one embodiment, the present invention relates to a method for treating dyslipidemia, wherein the patient requiring such treatment does not have co-existing type 1 or type 2 diabetes.

[0190] Furthermore, the present invention provides a drug for treating NALFD in patients requiring treatment of NALFD, comprising administering an escalating dose approximately once a week for at least about four weeks, and then administering a maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an incremental increase of 2.5 mg compared to the escalating dose, and provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of the drug.

[0191] In another embodiment, the present invention relates to a drug for treating NAFLD in patients requiring treatment for NAFLD, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0192] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating NAFLD in a patient requiring treatment of NAFLD, comprising administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0193] Another embodiment is a drug for treating NAFLD in patients who require treatment for NAFLD, a) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0194] Another embodiment is a drug for treating NAFLD in patients who require treatment for NAFLD, a) Administer the patient approximately 7.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0195] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating NAFLD in a patient requiring treatment of NAFLD, comprising administering a maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0196] Another embodiment is a drug for treating NAFLD in patients who require treatment for NAFLD, a) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 15.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0197] Another embodiment is a drug for treating NAFLD in patients who require treatment for NAFLD, a) Administer the patient approximately 12.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0198] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating NAFLD in a patient requiring treatment of NAFLD, comprising administering a maintenance dose of about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0199] In another embodiment, the present invention relates to a drug for treating NAFLD in patients requiring treatment for NAFLD, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) administering to the patient a gradually increasing dose of about 7.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then d) administering to the patient a maintenance dose of about 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0200] In another aspect, the present invention includes the medicament described in the previous paragraph, which does not include administering a gradually increasing dose of 7.5 mg.

[0201] In another aspect, the present invention is a medicament for treating NAFLD in a patient who requires treatment for NAFLD, a) administering to the patient a gradually increasing dose of about 2.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then b) administering to the patient a maintenance dose of about 5.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then c) administering to the patient a gradually increasing dose of about 7.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then d) administering to the patient a maintenance dose of about 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then e) administering to the patient a gradually increasing dose of about 12.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then f) administering to the patient a maintenance dose of about 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0202] In another aspect, the present invention includes the agent described in the previous paragraph, but does not include administering a gradually increasing dose of 7.5 mg. In another aspect, the present invention includes the agent described in the previous paragraph, but does not include administering a gradually increasing dose of 12.5 mg. In another aspect, the present invention includes the agent described in the previous paragraph, but does not include administering gradually increasing doses of 7.5 mg and 12.5 mg.

[0203] Furthermore, the present invention provides the use of tildesepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NASH in a patient who needs treatment for NASH, comprising administering a gradually increasing dose approximately once a week for at least about 4 weeks and then administering a maintenance dose approximately once a week for at least about 4 weeks, wherein the gradually increasing dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, and the maintenance dose after the gradually increasing dose is an incremental increase of 2.5 mg compared to that gradually increasing dose.

[0204] Furthermore, the present invention provides a medicament for treating NASH in a patient who needs treatment for NASH, comprising a) administering to the patient a gradually increasing dose of about 2.5 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then b) administering to the patient about 5.0 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0205] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating NASH in a patient requiring treatment of NASH, comprising administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0206] Another embodiment is a drug for treating NASH in patients who require treatment for NASH, a) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0207] Another embodiment is a drug for treating NASH in patients who require treatment for NASH, a) Administer the patient approximately 7.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) A method is provided comprising administering approximately 10.0 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least approximately 4 weeks.

[0208] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating NASH in a patient requiring treatment of NASH, comprising administering a maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0209] Another embodiment is a drug for treating NASH in patients who require treatment for NASH, a) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0210] Another embodiment is a drug for treating NASH in patients who require treatment for NASH, a) Administer the patient approximately 12.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0211] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for treating NASH in a patient requiring treatment of NASH, comprising administering a maintenance dose of about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0212] In another aspect, the present invention relates to a pharmacopoeia for treating NASH, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0213] In another embodiment, the present invention includes the agent described in the previous paragraph, but does not include administering an increasing dose of 7.5 mg.

[0214] In another aspect, the present invention relates to a drug for treating NASH in patients who require treatment for NASH, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter e) Administer the patient approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter f) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0215] In another aspect, the present invention includes the agent described in the previous paragraph, but does not include administering a gradually increasing dose of 7.5 mg. In another aspect, the present invention includes the agent described in the previous paragraph, but does not include administering a gradually increasing dose of 12.5 mg. In another aspect, the present invention includes the agent described in the previous paragraph, but does not include administering gradually increasing doses of 7.5 mg and 12.5 mg.

[0216] Furthermore, the present invention provides a use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient who requires such treatment, the medicament comprising administering a gradually increasing dose approximately once a week for at least about 4 weeks and then administering a maintenance dose approximately once a week for at least about 4 weeks, wherein the gradually increasing dose is selected from the group consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of tildepazide or a pharmaceutically acceptable salt thereof, the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg of tildepazide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the gradually increasing dose is an incremental increase of 2.5 mg compared to the gradually increasing dose.

[0217] The present invention provides a use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient who requires such treatment, a) administering to the patient a gradually increasing dose of about 2.5 mg of tildepazide or a pharmaceutically acceptable salt thereof approximately once a week for at least about 4 weeks, and then b) administering to the patient about 5.0 mg of tildepazide or a pharmaceutically acceptable salt thereof approximately once a week for at least about 4 weeks.

[0218] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient who requires the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, comprising administering a maintenance dose of about 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0219] Another embodiment is a drug for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in patients who require the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, a) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0220] Another embodiment is a drug for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in patients who require the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, a) Administer the patient approximately 7.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0221] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient who requires the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, comprising administering a maintenance dose of about 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0222] Another embodiment is a drug for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in patients who require the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, a) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0223] Another embodiment is a drug for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in patients who require the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, a) Administer the patient approximately 12.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0224] In another aspect, the present invention provides the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient who requires the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, comprising administering a maintenance dose of about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient about once a week for at least about four weeks.

[0225] In another aspect, the present invention relates to a drug for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in patients who require the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0226] In another embodiment, the present invention includes the agent described in the previous paragraph, but does not include administering an increasing dose of 7.5 mg.

[0227] In another aspect, the present invention relates to a drug for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in patients who require the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, a) Administer the patient approximately 2.5 mg of tilzepatide, or a pharmaceutically acceptable salt thereof, in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter b) Administer the patient a maintenance dose of approximately 5.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter c) Administer the patient approximately 7.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter d) Administer the patient a maintenance dose of approximately 10.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof approximately once a week for at least approximately 4 weeks, and thereafter e) Administer the patient approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof in gradually increasing doses, approximately once a week for at least approximately 4 weeks, and thereafter f) Providing the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of a drug, comprising administering a maintenance dose of approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof to the patient approximately once a week for at least approximately 4 weeks.

[0228] In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering an increasing dose of 7.5 mg. In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering an increasing dose of 12.5 mg. In another embodiment, the present invention includes the agent described in the previous paragraph, but does not involve administering increasing doses of 7.5 mg and 12.5 mg.

[0229] One embodiment of the above-mentioned drug for use in manufacturing is an escalating dose administered once a week for four weeks, with a maintenance dose of approximately 5.0 mg administered once a week for four weeks. A further embodiment of the present invention is an escalating dose administered once a week for four weeks, with a maintenance dose of approximately 7.5 mg administered once a week for four weeks, with a maintenance dose of approximately 10.0 mg administered once a week for four weeks. A further embodiment of the present invention is an escalating dose administered once a week for four weeks, with a maintenance dose of approximately 12.5 mg administered once a week for four weeks, with a maintenance dose of approximately 15.0 mg administered once a week for four weeks. A further embodiment of the present invention is an escalating dose administered once a week for four weeks, with doses of approximately 2.5 mg and approximately 7.5 mg administered once a week for four weeks, with maintenance doses of approximately 5.0 mg and approximately 10.0 mg administered once a week for four weeks. Further embodiments of the present invention include escalating doses administered once a week for four weeks, of approximately 2.5 mg, 5.0 mg, and 7.5 mg, and maintenance doses administered once a week for four weeks, of approximately 5.0 mg, 10.0 mg, and 15.0 mg.

[0230] Embodiment 1a provides a drug for preventing diabetes in patients requiring diabetes prevention, comprising administering an escalating dose approximately once a week for at least about two weeks, followed by a maintenance dose approximately once a week for at least two weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg compared to the escalating dose, in which tilzepatide or a pharmaceutically acceptable salt thereof is used in the manufacture of the drug.

[0231] Embodiment 2a provides a drug for preventing diabetes in patients requiring diabetes prevention, comprising administering an escalating dose approximately once a week for at least about four weeks, followed by a maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 5.0 mg compared to the escalating dose, and the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of the drug.

[0232] In Embodiment 3a, Embodiment 1a or 2a is used, with an increasing dose of approximately 2.5 mg and a maintenance dose of approximately 5.0 mg.

[0233] In Embodiment 4a, Embodiment 1a or 2a is used, with an increasing dose of approximately 7.5 mg and a maintenance dose of approximately 10.0 mg.

[0234] In Embodiment 5a, Embodiment 1a or 2a is used, with an increasing dose of approximately 12.5 mg and a maintenance dose of approximately 15.0 mg.

[0235] Embodiment 6a uses the same method as in Embodiment 3a, further comprising an escalating dose of approximately 7.5 mg and a maintenance dose of approximately 10.0 mg.

[0236] Embodiment 7a is the use of Embodiment 6a, further comprising an escalating dose of about 12.5 mg and a maintenance dose of about 15.0 mg. Embodiment 8a is the use of tilzepatide or a pharmaceutically acceptable salt thereof in the manufacture of the drug, comprising administering an escalating dose approximately once a week for at least about two weeks, and then administering a maintenance dose approximately once a week for at least two weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an incremental increase of 2.5 mg compared to the escalating dose.

[0237] Embodiment 9a provides a drug for treating chronic kidney disease in patients requiring treatment for chronic kidney disease, comprising administering at least one escalating dose approximately once a week for at least about four weeks, and then at least one maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an incremental increase of 5.0 mg compared to the escalating dose, wherein the drug is manufactured using tilzepatide or a pharmaceutically acceptable salt thereof.

[0238] In Embodiment 10a, Embodiment 8a or 9a is used, with an increasing dose of approximately 2.5 mg and a maintenance dose of approximately 5.0 mg.

[0239] In Embodiment 11a, Embodiment 8a or 9a is used, with an increasing dose of approximately 7.5 mg and a maintenance dose of approximately 10.0 mg.

[0240] In Embodiment 12a, Embodiment 8a or 9a is used, with an increasing dose of approximately 12.5 mg and a maintenance dose of approximately 15.0 mg.

[0241] Embodiment 13a uses the method of Embodiment 10a, further including an escalating dose of approximately 7.5 mg and a maintenance dose of approximately 10.0 mg.

[0242] Embodiment 14a is the use of Embodiment 13a, further comprising an escalating dose of about 12.5 mg and a maintenance dose of about 15.0 mg.

[0243] In another embodiment, the present invention provides tilzepatide or a pharmaceutically acceptable salt thereof for use in treating type 2 diabetes. In one embodiment, the present invention provides tilzepatide or a pharmaceutically acceptable salt thereof for use in treating type 2 diabetes in patients requiring treatment for type 2 diabetes, wherein an escalating dose is administered approximately once a week for a minimum of about four weeks, and thereafter a maintenance dose is administered approximately once a week for a minimum of about four weeks, the escalating dose being selected from the group consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose being selected from the group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an incremental increase of 2.5 mg compared to the escalating dose. In another embodiment, the present invention provides tilzepatide or a pharmaceutically acceptable salt thereof for use in improving blood glucose control. In another embodiment, the present invention provides tilzepatide or a pharmaceutically acceptable salt thereof for use in improving blood glucose control in patients requiring improved blood glucose control, wherein an escalating dose is administered approximately once a week for a minimum of about four weeks, and thereafter a maintenance dose is administered approximately once a week for a minimum of about four weeks, the escalating dose being selected from the group consisting of about 2.5 mg, about 7.5 mg and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose being selected from the group consisting of about 5.0 mg, about 10.0 mg and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an incremental increase of 2.5 mg compared to the escalating dose. In another embodiment, the present invention provides tilzepatide, or a pharmaceutically acceptable salt thereof, for use in improving weight management.In another embodiment, the present invention provides tilzepatide or a pharmaceutically acceptable salt thereof for use in improving weight management in patients requiring improved weight management, wherein an escalating dose is administered approximately once a week for a minimum of about four weeks, followed by a maintenance dose administered approximately once a week for a minimum of about four weeks, the escalating dose being selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose being selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, the maintenance dose after the escalating dose being an incremental increase of 2.5 mg compared to the escalating dose. In another embodiment, the present invention provides tilzepatide or a pharmaceutically acceptable salt thereof for use in treating chronic kidney disease. In another embodiment, the present invention provides tilzepatide or a pharmaceutically acceptable salt thereof for use in treating chronic kidney disease in patients requiring treatment for chronic kidney disease, wherein an escalating dose is administered approximately once a week for a minimum of about four weeks, followed by a maintenance dose administered approximately once a week for a minimum of about four weeks, the escalating dose being selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose being selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, the maintenance dose after the escalating dose being an incremental increase of 2.5 mg compared to the escalating dose. In another embodiment, the present invention provides tilzepatide or a pharmaceutically acceptable salt thereof for use in treating atherosclerosis.In another embodiment, the present invention provides tilzepatide or a pharmaceutically acceptable salt thereof for use in treating atherosclerosis in patients requiring treatment for atherosclerosis, wherein an escalating dose is administered approximately once a week for a minimum of about four weeks, followed by a maintenance dose administered approximately once a week for a minimum of about four weeks, the escalating dose being selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose being selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, the maintenance dose after the escalating dose being an incremental increase of 2.5 mg compared to the escalating dose. In another embodiment, the present invention provides tilzepatide or a pharmaceutically acceptable salt thereof for use in treating NAFLD. In another embodiment, the present invention provides tilzepatide or a pharmaceutically acceptable salt thereof for use in treating NAFLD in patients requiring treatment of NAFLD, wherein an escalating dose is administered approximately once a week for a minimum of about four weeks, followed by a maintenance dose administered approximately once a week for a minimum of about four weeks, the escalating dose being selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose being selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, the maintenance dose after the escalating dose being an incremental increase of 2.5 mg compared to the escalating dose. In another embodiment, the present invention provides tilzepatide or a pharmaceutically acceptable salt thereof for use in treating NASH.In another embodiment, the present invention provides tilzepatide or a pharmaceutically acceptable salt thereof for use in treating NASH in patients requiring treatment of NASH, wherein an escalating dose is administered approximately once a week for a minimum of about four weeks, followed by a maintenance dose administered approximately once a week for a minimum of about four weeks, the escalating dose being selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose being selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, the maintenance dose after the escalating dose being an incremental increase of 2.5 mg compared to the escalating dose. In another embodiment, the present invention provides tilzepatide or a pharmaceutically acceptable salt thereof for use in curing diabetes, inducing remission or regression of diabetes, or preventing diabetes. In another embodiment, the present invention provides tilzepatide or a pharmaceutically acceptable salt thereof for use in curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in patients who require the cure of diabetes, induction of remission or regression of diabetes, or prevention of diabetes, wherein an escalating dose is administered approximately once a week for a minimum of about four weeks, and thereafter a maintenance dose is administered approximately once a week for a minimum of about four weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an incremental increase of 2.5 mg compared to the escalating dose.

[0244] In one embodiment of the present invention for the use described above, the escalating dose administered once a week for four weeks is approximately 2.5 mg, and the maintenance dose administered once a week for four weeks is approximately 5.0 mg. In a further embodiment of the present invention, the escalating dose administered once a week for four weeks is approximately 7.5 mg, and the maintenance dose administered once a week for four weeks is approximately 10.0 mg. In another further embodiment of the present invention, the escalating dose administered once a week for four weeks is approximately 12.5 mg, and the maintenance dose administered once a week for four weeks is approximately 15.0 mg. In yet another embodiment of the present invention, the escalating doses administered once a week for four weeks are approximately 2.5 mg and approximately 7.5 mg, and the maintenance doses administered once a week for four weeks are approximately 5.0 mg and approximately 10.0 mg. Further embodiments of the present invention include escalating doses administered once a week for four weeks, of approximately 2.5 mg, 5.0 mg, and 7.5 mg, and maintenance doses administered once a week for four weeks, of approximately 5.0 mg, 10.0 mg, and 15.0 mg.

[0245] As used herein, “titration dose” or “escalation dose” means a dose less than the best desired effective dose for the patient. As used herein, the present invention is intended to assume that the “titration dose” or “escalation dose” may be the best desired effective dose, or a “maintenance dose” if such a dose is observed to be the desired effective dose for the patient, and such a dose is administered chronically for a period of more than four weeks.

[0246] As used herein, “maintenance dose” means both the dose that is the best desired effective dose for a patient, and the maintenance dose that may become an escalating dose if such a maintenance dose is less than the best desired effective dose. That is, if for a particular patient the maintenance dose of “about 5 mg” intended by the Invention is not the best desired effective dose, then that 5 mg maintenance dose would, in retrospect, become a titration dose as the next best maintenance dose intended by the Invention, for example, a dose for that particular patient that would increase from 7.5 mg in at least about two weeks to 10 mg in at least about two weeks. The Invention intends that patients who reach a maintenance dose of about 10 mg or about 15 mg may need to reduce those doses to lower maintenance doses, as determined by a physician or other healthcare provider.

[0247] Also provided herein are tilzepatide for the simultaneous, individual, or sequential combination use of one or more agents selected from metformin, thiazolidinediones, sulfonylurea, dipeptidyl peptidase-4 inhibitors, sodium glucose cotransporters, SGLT-2 inhibitors, growth and differentiation factor 15 modulators ("GDF15"), peptide tyrosine tyrosine modulators ("PYY"), modified insulin, amylin, dual amylin calcitonin receptor agonists, and oxytomodulin agonists ("OXM") for the treatment of conditions selected from the group consisting of type 2 diabetes mellitus, chronic kidney disease, atherosclerosis, NALFD, and NASH. Further provided herein are compounds of the present invention for use simultaneously, individually, or sequentially in combination with one or more agents selected from metformin, thiazolidinediones, sulfonylurea, dipeptidyl peptidase 4 inhibitors, sodium glucose cotransporters, SGLT-2 inhibitors, GDF15, PYY, modified insulin, amylin, dual amylin calcitonin receptor agonists, and OXM, in improving blood glucose control and / or weight management. Also provided herein are compounds of the present invention for use simultaneously, individually, or sequentially in combination with one or more agents selected from metformin, thiazolidinediones, sulfonylurea, dipeptidyl peptidase 4 inhibitors, sodium glucose cotransporters, SGLT-2 inhibitors, GDF15, PYY, modified insulin, amylin, dual amylin calcitonin receptor agonists, and OXM, in order to cure diabetes, induce remission or regression of diabetes, or prevent diabetes. In one embodiment, the compounds of this specification are provided in combination with a certain dose of one or more agents selected from metformin, thiazolidinediones, sulfonylurea, dipeptidyl peptidase 4 inhibitors, sodium glucose cotransporters, SGLT-2 inhibitors, GDF15, PYY, denatured insulin, amylin, dual amylin calcitonin receptor agonists, and OXM.

[0248] NAFLD and NASH treatment Non-alcoholic fatty liver disease ("NAFLD") is a liver disease characterized by the accumulation of fat in the liver of affected patients. Patients suffering from NAFLD may consume little to no alcohol, and in one embodiment, patients do not have comorbid diabetes. NAFLD is the leading cause of liver disease worldwide. Younossi et. al. Global epidemiology of nonalcoholic fatty liver disease—Meta-analytic assessment of prevalence, incidence, and outcomes; Hepatology (July 2016) 64:1;73-84. Non-alcoholic steatohepatitis ("NASH") is a type of NAFLD with a group of etiologies exhibiting macrodriphernal steatosis, inflammation, hepatocyte ballooning, and fibrosis. NASH can lead to cirrhosis and liver failure. Patients with NASH are more likely to develop cirrhosis and are established to have a higher risk of cardiovascular death and hepatocellular carcinoma. This non-alcoholic, non-viral cirrhosis is, in fact, one of the leading causes of liver transplantation.

[0249] NAFLD and NASH are progressive diseases characterized by the development of hepatic fibrosis as NAFLD progresses to NASH. The staging of NASH can be defined, for example, by the NASH CRN (Clinical Research Network). Fibrosis staging measures the amount and pattern of NASH fibrosis and parenchymal architectural remodeling of the patient's parenchyma. NASH is typically diagnosed in human patients using liver biopsy, and the diagnosis is predicted using MRI-derived proton density lipid percentage imaging ("MRI-PDFF"), plasma cytokeratin 18 (CK18) fragment levels as a biomarker of hepatocyte apoptosis, plasma Pro-C3 (N-terminal type III collagen propeptide) to predict fibrosis progression, and / or other biomarkers. (Vincent Wai-Sun Wong, et.al. Noninvasive biomarkers in NAFLD and NASH—current progress and future promise; Nature Reviews Gastroenterology & Hepatology; (29 May 2018)). NAFLD, a condition characterized by excessive lipid deposition in the liver, is typically evaluated using imaging techniques such as MRI-PDFF.

[0250] Currently, there are no approved medications specifically for the treatment of NASH. Current recommendations for NASH patients include diet and exercise. There is a need for medications to provide additional treatment options for patients with NAFLD and NASH.

[0251] The present invention provides a method for treating NAFLD, comprising administering an effective amount of tilzepatide or a pharmaceutically acceptable salt thereof to a patient in need of such treatment. The present invention also provides a method for treating NASH, comprising administering an effective amount of tilzepatide or a pharmaceutically acceptable salt thereof to a patient in need of such treatment. In one embodiment, the patient in need of treatment for NASH has comorbid type 2 diabetes. In one embodiment, the patient in need of treatment for NASH does not have type 2 diabetes.

[0252] Treatment of chronic kidney disease Chronic kidney disease ("CKD") is defined as a structural or functional abnormality of the kidneys that has been present for three months and affects a patient's health. CKD can be classified into five categories based on glomerular filtration rate ("GFR"). GFR can be estimated using biomarkers such as serum creatinine and albumin, albumin-to-creatinine ratio ("ACR"), and serum cystatin C, and moderate CKD (GFR 30-59 mL / min / 1.73m2) is classified as stage 3 CKD. In the adult population, decreased GFR is associated with an increased risk of cardiovascular disease ("CVD") independently of other cardiovascular ("CV") risk factors. CV mortality is 2-fold and 3-fold higher, respectively, in patients with stage 3 and stage 4 CKD compared to patients with normal renal function. Patients with CKD and established CVD have a much higher mortality rate compared to patients with CVD and normal renal function. Therefore, patients with CKD are considered high-risk (stage 3 CKD) or very high-risk (stage 4-5 CKD or undergoing dialysis). Treatment for patients with CKD typically includes diet, exercise, smoking cessation, antihypertensive drugs, and a combination of medications. Desired treatments for CKD are those that reduce inflammation, improve blood glucose control, and / or improve cellular function in such patients. Additional treatment options for patients with CKD are desired.

[0253] The present invention provides a method for treating CKD, comprising administering an effective amount of tilzepatide to a patient in need of such treatment. In one embodiment, the treatment is for a patient having stage 3 CKD. In one embodiment, the treatment is for a patient having stage 4 CKD. In one embodiment, the treatment is for a patient having stage 2 CKD. In one embodiment, the treatment is for a patient having stage 1 CKD.

[0254] Treatment of atherosclerosis Atherosclerosis is a condition that develops when plaque accumulates in the walls of arteries. This accumulation narrows the arteries and obstructs blood flow. Complications associated with atherosclerosis and its progression can lead to heart attacks or strokes. Despite recent advances in treatment options, cardiovascular disease remains a leading cause of death in people with diabetes. The present invention provides a method for treating atherosclerosis, comprising administering an effective dose of tilzepatide to a patient in need of treatment.

[0255] To cure diabetes, induce remission or regression of diabetes, or prevent diabetes, US9,474,780 teaches that tilzepatide is useful in the treatment of diabetes, and “treatment” includes slowing, slowing, stopping, or reversing the progression or severity of existing symptoms or impairments. Despite advances in the treatment of diabetes, many patients receiving such treatment are unable to achieve their blood glucose control targets or HbA1c targets.

[0256] US9,474,780 teaches that tilzepatide is useful in the treatment of diabetes, and “treatment” includes suppressing, slowing, stopping, or reversing the progression or severity of pre-existing symptoms or impairments. Despite advances in the treatment of diabetes, many patients receiving such treatment are unable to achieve their blood glucose control targets or HbA1c targets. This invention provides a cure for diabetes in which a patient receives treatment for diabetes using a tilzepatide dosing regimen comprising: administering an initial or escalating dose of 2.5 mg of tilzepatide once weekly for 4 weeks; administering a maintenance dose of 5.0 mg of tilzepatide once weekly for at least 4 weeks, but if the patient does not achieve their HbA1c target, administering an escalating dose of approximately 7.5 mg once weekly for at least 4 weeks; then administering a smaller maintenance dose of 10.0 mg of tilzepatide once weekly. If the patient does not achieve the HbA1c target after at least four weeks of treatment using a 10.0 mg dose once weekly, an escalating dose of 12.5 mg of tirzepatide may be administered once weekly for at least four weeks, followed by a maintenance dose of 15 mg once weekly until the HbA1c target is achieved for at least about two weeks, and such patients maintain the HbA1c target even after discontinuing all drugs approved for use in the treatment of diabetes or glycemic control. As used herein, terms such as “diabetic drug” and “diabetic medicine” mean drugs approved by the relevant regulatory authority for use in the treatment of glycemic control or type II diabetes. In one embodiment, the HbA1c measurement of a patient treated for diabetes is about 5.9% or less. In one embodiment, the patient maintains the HbA1c target level for at least one month without further administration of tirzepatide. In one embodiment, a patient who has previously been treated for diabetes with tirzepatide maintains the glycemic target for at least one month without further administration of tirzepatide or other diabetes drugs. In one embodiment, the patient maintains their blood glucose target for at least six months without administering further tilzepatide or other diabetes medications.

[0257] As used herein, terms such as “diabetic drug” and “diabetic medicine” mean drugs approved by the relevant regulatory authority for use in blood glucose control or the treatment of type II diabetes. In one embodiment, the HbA1c measurement of a patient treated for diabetes is approximately 5.9% or less. In one embodiment, the patient maintains the HbA1c target level for at least one month without further administration of tilzepatide. In one embodiment, a patient who has previously been treated for diabetes with tilzepatide maintains the blood glucose target for at least one month without further administration of tilzepatide or other diabetes drugs. In one embodiment, the patient maintains the blood glucose target for at least six months without further administration of tilzepatide or other diabetes drugs.

[0258] The doses of the present invention are likely to have specific concentrations of 5 mg / mL, 10 mg / mL, 15 mg / mL, 20 mg / mL, 25 mg / mL, and 30 mg / mL. Such compositions may be provided in pre-filled syringes. Such pre-filled syringes may be useful for administering 0.5 milliliters of such compositions per patient dose. The doses of the present invention are typically administered subcutaneously. The doses are typically administered using a pre-filled disposable pen, a reusable pen, or an auto-pen injector. In one embodiment, the device is an auto-injector described by U.S. Patent No. 8,734,394.

[0259] As used herein, “Tilzepatide” means the GIP / GLP1 dual agonist peptide described in US9,474,780 and CAS Registry Number: 2023788-19-2.

[0260] Chilzepatide is described in Example 1 of US9,474,780 and has the following sequence: YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS In the sequence, X1 is Aib, X2 is Aib, and the K at position 20 is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)1-CO-(CH2) 18 The -CO2H molecule is chemically modified through the bonding of its K side chain to the epsilon-amino group, and the C-terminal amino acid is amidated as a C-terminal primary amide (SEQ ID NO: 1).

[0261] As used herein, the term “administration” means administration by any other individual, including a nurse, healthcare provider, patient, or self-administration. This includes not only delivery into the body, but also prescription, dispensing, or assistance in delivery.

[0262] As used herein, the terms “increased dose,” “increased maintenance dose,” “increased titration dose,” and “increased escalation dose” mean the respective dose increase by a nurse, healthcare provider, patient, or any other individual.

[0263] As used herein, “pharmaceutically acceptable salt” is well known to those skilled in the art. In one embodiment, the pharmaceutically acceptable salt is trifluoroacetate tylzepatide salt. In one embodiment, it is tylzepatide as a non-salt.

[0264] As used herein, the term “biomarker” means a laboratory measurement that reflects the activity of a disease process. Biomarkers can be used to diagnose a disease or condition and typically correlate quantitatively (directly or inversely) with disease progression. In a clinical trial setting, biomarkers are measures of the effectiveness of a particular treatment and may correlate with, but not necessarily precisely with, actual clinical endpoints; in other words, biomarkers are a substitute for clinical endpoints.

[0265] As used herein, terms such as “treatment,” “to treat,” and “to treat” include delaying or reducing the progression of a disease or disorder. This includes alleviating, improving, or reducing one or more symptoms of a disorder or condition, even if the disorder or condition is not resolved or its progression is not slowed.

[0266] As used herein, “cure of diabetes” means that a patient using tilzepatide for the treatment of diabetes reaches a glycemic control treatment goal. Tilzepatide treatment for curing diabetes can prevent, reduce the severity of, or induce remission of diabetes in such patients. In one embodiment, tilzepatide treatment slows the progression of diabetes in patients requiring such treatment. In one embodiment, a patient using tilzepatide for the treatment of diabetes achieves a glycemic control treatment goal and does not require concomitant diabetes medications to maintain the glycemic control goal. In one embodiment, a patient using tilzepatide for the treatment of diabetes reaches at least a glycemic control treatment goal, and the treatment goal is maintained with discontinuation of treatment using tilzepatide and all other diabetes medications. In one embodiment, a patient using tilzepatide for the treatment of diabetes reaches at least a glycemic control treatment goal, and the treatment goal is maintained for at least about one month with discontinuation of treatment using tilzepatide and all other diabetes medications. In one embodiment, patients using tilzepatide for the treatment of diabetes reach at least the glycemic control treatment target, and the treatment target is maintained for at least about 6 months upon discontinuation of treatment using tilzepatide and all other diabetes medications. In one embodiment, the patient is unable to achieve the glycemic target before tilzepatide treatment. In one embodiment, the patient is unable to achieve the glycemic target using oral diabetes medications. In one embodiment, the patient is unable to achieve the glycemic target using metformin treatment. In one embodiment, the patient's glycemic target is less than about 5.9% HbA1c.

[0267] As used herein, “glycemic control” means maintaining or reducing a patient’s HbA1c level, and “improvement” in glycemic control means a decrease in HbA1c.

[0268] As used herein, "weight management" refers to the management of an individual's obesity, and "improvement" of weight management refers to weight loss.

[0269] As used herein, "HbA1c" refers to the level of glycated hemoglobin that occurs when hemoglobin binds to glucose in the blood. HbA1c levels are a commonly used measure of glycemic control in patients with diabetes, and a decrease in HbA1c levels generally indicates improved glycemic control. In relation to the method of the present invention, the method of the present invention results in a reduction of HbA1c. In certain embodiments, the reduction in HbA1c is a decrease compared to the HbA1c level resulting from treatment with a lower dose of tylzepatide.

[0270] As used herein, “patient” or “patients” refers to mammals in need of treatment for a condition or disorder. In one embodiment, the patient is a human being having a disease or condition that would benefit from treatment with tilzepatide.

[0271] The term "LOCF," or last observation carried forward, is recognized by experienced statisticians as a statistical analysis method for imputing missing data. The term "ITT," or intention to treat, is recognized by experienced statisticians as an analysis method in which participants are analyzed according to the group to which they were initially assigned.

[0272] Preparation #1: Tilzepatide composition containing NaCl The compositions are prepared substantially as described herein. Compositions containing 5, 10, 15, 20, 15, and 30 mg / mL of tilzepatide each contain the components listed in Table 1. Acids or bases are optionally added to achieve the desired pH range. An appropriate amount (qs) of water is added to the total final volume of 1 ml. [Table 1]

[0273] Preparation #2-Tilzepatide composition containing propylene glycol The compositions are prepared substantially as described herein. Compositions providing 5, 10, 15, 20, 15, and 30 mg / mL of tilzepatide each contain the components listed in Table 2. Acids or bases are optionally added to achieve the desired pH range. Water is added in appropriate amounts to a total final volume of 1 milliliter. [Table 2]

[0274] Clinical trial supporting the maintenance dose implementation (NCT03131687) A 6-month (26-week) Phase 2 double-blind clinical trial is designed to evaluate the safety, efficacy, and PK / PD of tilzepatide administered subcutaneously once weekly at four dose levels (1 mg, 5 mg, 10 mg, and 15 mg, respectively) compared to dulaglutide 1.5 mg once weekly (QW) and placebo QW in patients with T2DM who have inadequate glycemic control through diet and exercise, with or without a stable dose of metformin. The dose of tilzepatide will be up-titrated to the maintenance dose using the following weekly dose increments. [Table 3]

[0275] This study will also include a 4-week follow-up period. In addition to safety and efficacy for treating T2DM, efficacy endpoints will include the effects of tilzepatide on HbA1c, FBG, body weight, lipids, and waist circumference compared to placebo and dulaglutide 1.5 mg. This study will also evaluate the effects of tilzepatide on GI tolerability, hypoglycemia, hypersensitivity reactions, pancreatic safety, and the development of anti-drug antibodies due to treatment. Model-based dose-response analysis will be performed to predict the potential for significant HbA1c reduction and weight loss in longer studies.

[0276] statistical analysis Efficacy: The primary efficacy outcome of HbA1c change from baseline to the 26-week endpoint is analyzed using a Bayesian dose-response model. The analysis is performed with the intention of processing a population (mITT) analysis set. The analysis supporting the primary efficacy outcome of the mITT dataset is fixed as a body mass index (BMI) (<30 kg / m²). 2 , ≥30kg / m 2 This model includes post-baseline measurements (MMRM) using metformin use, treatment, visits, interaction with treatment and visits, baseline HbA1c as a covariate, and patient as a random effect.

[0277] The mean weight change from baseline at 12 and 26 weeks, and the mean change in HbA1c from baseline at 12 weeks, will be analyzed using a dose-response model similar to that used in the primary analysis. The proportion of patients with ≥5% or ≥10% weight loss, the proportion of patients who reached the target of ≤6.5% or ≤7.0% HbA1c at 26 weeks, or the proportion of patients requiring rescue therapy will be analyzed using logistic regression with fixed effects of treatment and stratification, with baseline as a covariate. The mean percentage changes from baseline in FBG (fasting blood glucose), SMBG (self-monitoring blood glucose) levels, waist circumference, and lipids from baseline to 12 and 26 weeks will be analyzed using MMRM similar to that used in the primary analysis.

[0278] Abbreviations in the table: Dula 1.5mg = 1.5mg of dulaglutide once a week, LY means tilzepatide, LY 1mg = 1mg of tilzepatide once a week, LY 5mg = 5mg once a week, LY 10mg = tilzepatide once a week, with a maximum dose of 10mg in the escalating dose group, LY 15mg = tilzepatide once a week, with a maximum dose of 15mg in the escalating dose group, LOCF = last observation-carried-forward, N = number of patients, pbo = placebo, 26 weeks = mITT on-treatment data at 26 weeks excluding data after discontinuation of the investigational drug or initiation of rescue medication, mITT = intent-to-treat, SD = standard deviation. In Table 4, n = number of patients in the population with baseline and post-baseline values ​​at the specified time point. In Table 6, LY10mg = tirzepatide once a week, with a maximum dose of 10mg, escalating dose: (5mg at weeks 0 and 1), LY15mg = tirzepatide once a week, with a maximum dose of 15mg, escalating dose: (5mg at weeks 0 and 1, 10mg from weeks 2 to 5), N = number of patients in a specific group, m = number of patients who experienced a new event during the interval, FolUp = follow-up, T / Wk = time range, (weeks), % = percentage of patients who experienced a new event during the interval and spent at least a certain amount of time in the treatment group. In Table 7, n is the number of patients with an event that meets the criteria, N is the number of patients in the population, and % is the percentage of patients in the treatment group who experienced an event. [Table 4]

[0279] The data in Table 3 support the finding that tilzepatide at doses of 5 mg, 10 mg, and 15 mg significantly reduced HbA1c from baseline, and was significantly different from placebo. Those skilled in the art will understand that HbA1c levels below 5.7% are consistent with levels observed in patients without diabetes. The tilzepatide dose groups were also significantly different from those of dulaglutide 1.5 mg.

[0280] The percentage of patients achieving the HbA1c treatment target in Table 3 indicates that more patients in the tilzepatide 15 mg group, who continued taking the investigational drug, were able to achieve the HbA1c treatment target of ≤5.7% compared to any other treatment group. [Table 5]

[0281] As shown in Table 4, as expected from the observed changes in HbA1c, doses of 5 mg, 10 mg, and 15 mg of tylzepatide significantly reduced fasting serum glucose compared to placebo and dulaglutide 1.5 mg. [Table 6]

[0282] Table 5 summarizes the percentage of patients who achieved weight loss targets of ≥5%, ≥10%, and ≥15% at 26 weeks. Doses of 5 mg, 10 mg, and 15 mg of tilzepatide significantly reduced body weight from baseline and differed significantly from placebo. The tilzepatide 5 mg, 10 mg, and 15 mg groups also differed significantly from the dulaglutide 1.5 mg group.

[0283] As shown in Table 5, which summarizes the clinical trials, the majority of patients in the tilzepatide 15 mg group achieved an average weight loss of more than 15%. [Table 7]

[0284] Table 6 shows the favorable effect of using the methods described herein on the incidence of gastrointestinal adverse events. [Table 8]

[0285] The decrease in appetite is a centrally mediated effect. The data shown in Table 7, reported from clinical trials, suggest that tirzepatide has a centrally mediated effect. Centrally mediated tirzepatide activity may provide an additional treatment option for patients seeking therapies that offer centrally mediated GIP / GLP1 agonist activity.

[0286] In NCT03131687, the 15 mg dose was associated with a high GI AE and a high frequency of patients discontinuing the study treatment early after relatively short dose escalations. A 15 mg dose with a more tolerable tolerability profile is desirable. Data from NCT03131687 support a 15 mg dose as the best clinically relevant maintenance dose, as intended by the present invention. Elevation schemes as asserted herein were investigated to facilitate an acceptable and tolerable 15 mg maintenance dose. See clinical trial immediately below (NCT03311724).

[0287] 2.5 Clinical trial supporting escalating doses (NCT03311724) This is a 12-week treatment plan, consisting of a 1-week screening (visit 1), followed by a 1-week induction period (visit 2), then 12 weeks of treatment (visits 3-10, including telephone visits), followed by a 4-week safety follow-up. This is a Phase 2 trial designed to investigate the efficacy and tolerability of weekly subcutaneous tilzepatide compared to placebo in patients with type 2 diabetes whose glycemic control is inadequate with diet and exercise alone or with a stable dose of metformin. The trial was designed and conducted to improve the escalation scheme as follows: [Table 9] [Table 10]

[0288] As shown in Table 8, after 12 weeks of treatment including an 8-week dose escalation period, the placebo-adjusted change in HbA1c from baseline at 12 mg and 15 mg tilzepatide doses was statistically significant and clinically meaningful. [Table 11]

[0289] As shown in Table 9, at 12 weeks, both doses of tilzepatide resulted in a significant decrease in body weight compared to placebo. [Table 12]

[0290] As shown in Table 10, the most common adverse events were gastrointestinal events, including nausea, vomiting, and diarrhea. Most of these vents were mild to moderate. No patients discontinued the trial due to tolerable gastrointestinal adverse events or other adverse vents.

[0291] Based on these data from NCT03311724, we further support the escalation scheme using a dose increment of 2.5 mg per 4 weeks.

[0292] biomarkers Clinical trials measure clinically relevant biomarkers to further support the use of tirzepatide for the treatment of chronic kidney disease. In the NCT03131687 trial, no decrease in eGFR was observed at any dose. Laboratory measurements support the use of tirzepatide in the treatment of chronic kidney disease. Clinically relevant biomarkers are measured to evaluate and support the use of tirzepatide in the treatment of atherosclerosis. Clinically relevant triglyceride levels decrease in all tirzepatide treatment groups. Clinical observations support the possibility that tirzepatide may be beneficial for use in the treatment of atherosclerosis.

[0293] Biomarkers predicting NAFLD will be observed during clinical trials to demonstrate the beneficial effects of tilzepatide in the treatment of NAFLD. Biomarkers predicting NASH will be observed during clinical trials to demonstrate the beneficial effects of tilzepatide in the treatment of NAFLD. HbA1c levels in tilzepatide-treated patients who have achieved their glycemic control goals and discontinued the use of diabetes medications will be measured during follow-up to verify the cure of diabetes in such patients.

[0294] Example 1 Clinical Dosage Plan A clinical trial to investigate the three maintenance doses (5.0 mg, 10.0 mg, and 15.0 mg) of the present invention in the administration plan of the present invention will be conducted as follows.

[0295] The starting dose of tilzepatide is 2.5 mg once weekly for 4 weeks, and then increased to 5 mg once weekly during the trial period in the low-dose group.

[0296] In the 10 mg group, the starting dose of tilzepatide was 2.5 mg once weekly for 4 weeks, after which the dose was increased by 2.5 mg every 4 weeks until the dose reached 10 mg and maintained for the duration of the study (5 mg once weekly for 4 weeks, then 7.5 mg once weekly for 4 weeks).

[0297] In the 15 mg group, the starting dose of tilzepatide is 2.5 mg once weekly for 4 weeks, after which the dose is increased by 2.5 mg every 4 weeks until the 15 mg dose of tilzepatide is reached and maintained for the duration of the study (5 mg once weekly for 4 weeks, then 7.5 mg once weekly for 4 weeks, then 10 mg once weekly for 4 weeks, then 12.5 mg once weekly for 4 weeks). In patients who cannot tolerate the 15 mg dose, the maintenance dose can be reduced to 10 mg.

[0298] array Sequence ID 1 Chilzepatid YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS In the sequence, X1 is Aib, X2 is Aib, and the K at position 20 is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)1-CO-(CH2) 18 The C-terminal amino acid is chemically modified through the bonding of the K side chain of -CO2H to the epsilon-amino group, and is amidated as a C-terminal primary amide.

Claims

1. A method for treating type 2 diabetes in a patient requiring treatment for type 2 diabetes, comprising administering an escalation dose approximately once a week for at least about two weeks, and then administering a maintenance dose approximately once a week for at least about two weeks, wherein the escalation dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

2. The method for treating type 2 diabetes in patients requiring treatment of type 2 diabetes, comprising administering at least one escalating dose approximately once a week for at least about four weeks, and then at least one maintenance dose approximately once a week for at least about four weeks thereafter, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

3. The method according to claim 1 or 2, wherein the escalating dose is approximately 2.5 mg and the maintenance dose is approximately 5.0 mg.

4. The method according to claim 1 or 2, wherein the escalating dose is approximately 7.5 mg and the maintenance dose is approximately 10.0 mg.

5. The method according to claim 1 or 2, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

6. Tilzepatide or a pharmaceutically acceptable salt thereof for use in treating type 2 diabetes in patients requiring treatment for type 2 diabetes, wherein at least one escalating dose is administered approximately once a week for at least about two weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about two weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

7. Tilzepatide or a pharmaceutically acceptable salt thereof for use according to claim 6, wherein at least one escalating dose is administered approximately once a week for at least about four weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

8. Tilzepatide for use according to claim 6 or 7, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

9. Tilzepatide for use according to claim 6 or 7, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

10. Tilzepatide for use according to claim 6 or 7, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

11. A method for inducing remission or regression of diabetes in a patient requiring induction of remission or regression of diabetes, comprising administering an escalating dose approximately once a week for at least about two weeks, and then administering a maintenance dose approximately once a week for at least about two weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

12. The method according to claim 11 for inducing remission or regression of diabetes in a patient requiring induction of remission or regression of diabetes, comprising administering at least one escalating dose approximately once a week for at least about four weeks, and then at least one maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

13. The method according to claim 11 or 12, wherein the escalating dose is approximately 2.5 mg and the maintenance dose is approximately 5.0 mg.

14. The method according to claim 11 or 12, wherein the escalating dose is approximately 7.5 mg and the maintenance dose is approximately 10.0 mg.

15. The method according to claim 11 or 12, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

16. Tilzepatide or a pharmaceutically acceptable salt thereof for use in inducing remission or regression of diabetes in patients requiring induction of remission or regression of diabetes, wherein at least one escalating dose is administered approximately once a week for at least about two weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about two weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

17. The use of tilzepatide or a pharmaceutically acceptable salt thereof according to claim 16, wherein at least one escalating dose is administered approximately once a week for at least about four weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

18. Tilzepatide for use according to claim 16 or 17, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

19. Tilzepatide for use according to claim 16 or 17, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

20. Tilzepatide for use according to claim 16 or 17, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

21. A method for preventing diabetes in patients requiring prevention of diabetes, comprising administering an increasing dose approximately once a week for at least about two weeks, and then administering a maintenance dose approximately once a week for at least about two weeks, wherein the increasing dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

22. The method for preventing diabetes mellitus in a patient requiring prevention of diabetes mellitus, comprising administering at least one escalating dose approximately once a week for at least about four weeks, and then, after the escalating dose, at least one maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

23. The method according to claim 20 or 21, wherein the escalating dose is approximately 2.5 mg and the maintenance dose is approximately 5.0 mg.

24. The method according to claim 20 or 21, wherein the escalating dose is approximately 7.5 mg and the maintenance dose is approximately 10.0 mg.

25. The method according to claim 20 or 21, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

26. Tilzepatide or a pharmaceutically acceptable salt thereof for use in preventing diabetes in patients requiring prevention of diabetes, wherein at least one escalating dose is administered approximately once a week for at least about two weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about two weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

27. Tilzepatide or a pharmaceutically acceptable salt thereof for use according to claim 26, wherein at least one escalating dose is administered approximately once a week for at least about four weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

28. Tilzepatide for use according to claim 26 or 27, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

29. Tilzepatide for use according to claim 26 or 27, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

30. Tilzepatide for use according to claim 26 or 27, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

31. A method for improving weight management in a patient requiring improved weight management, comprising administering an escalating dose approximately once a week for at least about two weeks, and then administering a maintenance dose approximately once a week for at least about two weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

32. The method according to claim 31 for improving weight management in a patient requiring improved weight management, comprising administering at least one escalating dose approximately once a week for at least about four weeks, and then at least one maintenance dose approximately once a week for at least about four weeks thereafter, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

33. The method according to claim 30 or 31, wherein the escalating dose is approximately 2.5 mg and the maintenance dose is approximately 5.0 mg.

34. The method according to claim 30 or 31, wherein the escalating dose is approximately 7.5 mg and the maintenance dose is approximately 10.0 mg.

35. The method according to claim 30 or 31, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

36. Tilzepatide or a pharmaceutically acceptable salt thereof for use in improving weight management in patients requiring improved weight management, wherein at least one escalating dose is administered approximately once a week for at least about two weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about two weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

37. The use of tilzepatide or a pharmaceutically acceptable salt thereof according to claim 36, wherein at least one escalating dose is administered approximately once a week for at least about four weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

38. Tilzepatide for use according to claim 36 or 37, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is approximately 2.5 mg and the maintenance dose is approximately 5.0 mg.

39. Tilzepatide for use according to claim 36 or 37, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is approximately 7.5 mg and the maintenance dose is approximately 10.0 mg.

40. Tilzepatide for use according to claim 36 or 37, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

41. A method for treating chronic kidney disease, comprising administering an effective amount of tilzepatide or a pharmaceutically acceptable salt thereof to a patient in need of such treatment.

42. The method according to claim 41, comprising administering an increasing dose approximately once a week for at least about two weeks, and then administering a maintenance dose approximately once a week for at least about two weeks, wherein the increasing dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

43. The method for treating chronic kidney disease in a patient requiring treatment for chronic kidney disease, as described in claim 41, comprising administering at least one escalating dose approximately once a week for at least about four weeks, and then at least one maintenance dose approximately once a week for at least about four weeks thereafter, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

44. The method according to claim 42 or 43, wherein the escalating dose is approximately 2.5 mg and the maintenance dose is approximately 5.0 mg.

45. The method according to claim 42 or 43, wherein the escalating dose is approximately 7.5 mg and the maintenance dose is approximately 10.0 mg.

46. The method according to claim 42 or 43, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

47. Tilzepatide or a pharmaceutically acceptable salt thereof for use in treating chronic kidney disease in patients requiring treatment for chronic kidney disease, wherein at least one escalating dose is administered approximately once a week for at least about two weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about two weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

48. Tilzepatide or a pharmaceutically acceptable salt thereof for use according to claim 47, wherein at least one escalating dose is administered approximately once a week for at least about four weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

49. Tilzepatide for use according to claim 47 or 48, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

50. Tilzepatide for use according to claim 47 or 48, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is approximately 7.5 mg and the maintenance dose is approximately 10.0 mg.

51. Tilzepatide for use according to claim 47 or 48, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

52. A method for treating atherosclerosis, comprising administering an effective amount of tilzepatide or a pharmaceutically acceptable salt thereof to a patient in need of such treatment.

53. The method according to claim 52, comprising administering an increasing dose approximately once a week for at least about two weeks, and then administering a maintenance dose approximately once a week for at least about two weeks, wherein the increasing dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

54. The method for treating atherosclerosis in a patient requiring treatment for atherosclerosis, as described in claim 52, comprising administering at least one escalating dose approximately once a week for at least about four weeks, and then at least one maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, with the maintenance dose after the escalating dose being an increment of 2.5 mg.

55. The method according to claim 53 or 54, wherein the escalating dose is approximately 2.5 mg and the maintenance dose is approximately 5.0 mg.

56. The method according to claim 53 or 54, wherein the escalating dose is approximately 7.5 mg and the maintenance dose is approximately 10.0 mg.

57. The method according to claim 53 or 54, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

58. Tilzepatide or a pharmaceutically acceptable salt thereof for use in treating atherosclerosis in patients requiring treatment for atherosclerosis, wherein at least one escalating dose is administered approximately once a week for at least about two weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about two weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

59. The use of tilzepatide or a pharmaceutically acceptable salt thereof according to claim 58, wherein at least one escalating dose is administered approximately once a week for at least about four weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

60. Tilzepatide for use according to claim 58 or 59, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

61. Tilzepatide for use according to claim 58 or 59, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is approximately 7.5 mg and the maintenance dose is approximately 10.0 mg.

62. Tilzepatide for use according to claim 58 or 59, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

63. A method for treating non-alcoholic fatty liver disease, comprising administering an effective amount of tilzepatide or a pharmaceutically acceptable salt thereof to a patient in need of such treatment.

64. The method according to claim 63, comprising administering an increasing dose approximately once a week for at least about two weeks, and then administering a maintenance dose approximately once a week for at least about two weeks, wherein the increasing dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

65. The method for treating non-alcoholic fatty liver disease in a patient requiring treatment for non-alcoholic fatty liver disease, as described in claim 63, comprising administering at least one escalating dose approximately once a week for at least about four weeks, and then at least one maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

66. The method according to claim 64 or 65, wherein the escalating dose is approximately 2.5 mg and the maintenance dose is approximately 5.0 mg.

67. The method according to claim 64 or 65, wherein the escalating dose is approximately 7.5 mg and the maintenance dose is approximately 10.0 mg.

68. The method according to claim 64 or 65, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

69. Tilzepatide or a pharmaceutically acceptable salt thereof for use in treating non-alcoholic fatty liver disease in patients requiring treatment for non-alcoholic fatty liver disease, wherein at least one escalating dose is administered approximately once a week for at least about two weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about two weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

70. Tilzepatide or a pharmaceutically acceptable salt thereof for use according to claim 69, wherein at least one escalating dose is administered approximately once a week for at least about four weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

71. Tilzepatide for use according to claim 69 or 70, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is approximately 2.5 mg and the maintenance dose is approximately 5.0 mg.

72. Tilzepatide for use according to claim 69 or 70, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is approximately 7.5 mg and the maintenance dose is approximately 10.0 mg.

73. Tilzepatide for use according to claim 69 or 70, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

74. A method for treating non-alcoholic steatohepatitis, comprising administering an effective amount of tilzepatide or a pharmaceutically acceptable salt thereof to a patient in need of such treatment.

75. The method according to claim 74, comprising administering an increasing dose approximately once a week for at least about two weeks, and then administering a maintenance dose approximately once a week for at least about two weeks, wherein the increasing dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

76. The method for treating non-alcoholic steatohepatitis in a patient requiring treatment for non-alcoholic steatohepatitis, comprising administering at least one escalating dose approximately once a week for at least about four weeks, and then at least one maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, with the maintenance dose after the escalating dose being an increment of 2.5 mg.

77. The method according to claim 75 or 76, wherein the escalating dose is approximately 2.5 mg and the maintenance dose is approximately 5.0 mg.

78. The method according to claim 75 or 76, wherein the escalating dose is approximately 7.5 mg and the maintenance dose is approximately 10.0 mg.

79. The method according to claim 75 or 76, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

80. Tilzepatide or a pharmaceutically acceptable salt thereof for use in treating non-alcoholic steatohepatitis in patients requiring treatment for non-alcoholic steatohepatitis, wherein at least one escalating dose is administered approximately once a week for at least about two weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about two weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

81. Tilzepatide or a pharmaceutically acceptable salt thereof for use according to claim 80, wherein at least one escalating dose is administered approximately once a week for at least about four weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

82. Tilzepatide for use according to claim 80 or 81, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

83. Tilzepatide for use according to claim 80 or 81, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

84. Tilzepatide for use according to claim 80 or 81, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

85. A method for treating obesity in a patient requiring treatment for obesity, comprising administering an increasing dose approximately once a week for at least about two weeks, and then administering a maintenance dose approximately once a week for at least about two weeks, wherein the increasing dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

86. The method for treating obesity in a patient requiring treatment for obesity, as described in claim 85, comprising administering at least one escalating dose approximately once a week for at least about four weeks, and then at least one maintenance dose approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

87. The method according to claim 85 or 86, wherein the escalating dose is approximately 2.5 mg and the maintenance dose is approximately 5.0 mg.

88. The method according to claim 85 or 86, wherein the escalating dose is approximately 7.5 mg and the maintenance dose is approximately 10.0 mg.

89. The method according to claim 85 or 86, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

90. Tilzepatide or a pharmaceutically acceptable salt thereof for use in treating obesity in patients requiring treatment for obesity, wherein at least one escalating dose is administered approximately once a week for at least about two weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about two weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

91. Tilzepatide or a pharmaceutically acceptable salt thereof for use according to claim 90, wherein at least one escalating dose is administered approximately once a week for at least about four weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

92. Tilzepatide for use according to claim 90 or 91, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

93. Tilzepatide for use according to claim 90 or 91, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is approximately 7.5 mg and the maintenance dose is approximately 10.0 mg.

94. Tilzepatide for use according to claim 90 or 91, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

95. A method for treating diabetic nephropathy in a patient requiring treatment for diabetic nephropathy, comprising administering an escalating dose approximately once a week for at least about two weeks, and then administering a maintenance dose approximately once a week for at least about two weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

96. The method for treating diabetic nephropathy in a patient requiring treatment for diabetic nephropathy, comprising administering at least one escalating dose approximately once a week for at least about four weeks, and then at least one maintenance dose approximately once a week for at least about four weeks thereafter, wherein the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

97. The method according to claim 95 or 96, wherein the escalating dose is approximately 2.5 mg and the maintenance dose is approximately 5.0 mg.

98. The method according to claim 95 or 96, wherein the escalating dose is approximately 7.5 mg and the maintenance dose is approximately 10.0 mg.

99. The method according to claim 95 or 96, wherein the escalating dose is approximately 12.5 mg and the maintenance dose is approximately 15.0 mg.

100. Tilzepatide or a pharmaceutically acceptable salt thereof for use in treating diabetic nephropathy in patients requiring treatment for diabetic nephropathy, wherein at least one escalating dose is administered approximately once a week for at least about two weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about two weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof.

101. The use of tilzepatide or a pharmaceutically acceptable salt thereof according to claim 100, wherein at least one escalating dose is administered approximately once a week for at least about four weeks, and thereafter at least one maintenance dose is administered approximately once a week for at least about four weeks, wherein the escalating dose is selected from the group consisting of approximately 2.5 mg, approximately 7.5 mg, and approximately 12.5 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose is selected from the group consisting of approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg of tilzepatide or a pharmaceutically acceptable salt thereof, and the maintenance dose after the escalating dose is an increment of 2.5 mg.

102. Tilzepatide for use according to claim 100 or 101, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

103. Tilzepatide for use according to claim 100 or 101, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is approximately 7.5 mg and the maintenance dose is approximately 10.0 mg.

104. Tilzepatide for use according to claim 100 or 101, or a pharmaceutically acceptable salt thereof, wherein the escalating dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

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