Methods of using a GIP / GLP1 co-agonist for therapy

Abstract

The present invention provides a method for improving glycemic control in a patient in need thereof by administering tirzepatide or a pharmaceutically acceptable salt thereof. The present invention also provides a method for improving weight management in a patient in need thereof by administering tirzepatide or a pharmaceutically acceptable salt thereof. Furthermore, the present invention also provides a method for treating a condition selected from atherosclerosis, chronic kidney disease, NAFLD, and NASH. Furthermore, a method for preventing diabetes or inducing remission of diabetes, comprising administering tirzepatide or a pharmaceutically acceptable salt thereof, is also provided. Furthermore, a dosing regimen for improving glycemic control, improving weight management, and / or treating dyslipidemia is also provided.

Description

Technical Field

[0001] The present invention provides a method 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 a method of using a novel dosing regimen of a GIP / GLP1 dual agonist peptide, tirzepatide, or a pharmaceutically acceptable salt thereof for treating type 2 diabetes. Furthermore, the present invention provides a novel medical use of tirzepatide, or a pharmaceutically acceptable salt thereof. More specifically, the present invention provides a method 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 a method for treating diabetes in a specific 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 a composition 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 GIP / GLP1 coagonists for treating diabetes, obesity, and other conditions. US9474780 describes and claims tirzepatide.

[0004] It is well known that GLP1 therapy is associated with nausea, vomiting, and / or diarrhea. For example, in one study, it was reported that all GLP-1 receptor agonist dosing regimens significantly increased the incidence of gastrointestinal adverse events. Diabetes Technol Ther. 2015 Jan;17(1):35-42. Also, previous clinical trials of GIP / GLP1 co-agonist compounds have been conducted, and it has been found that tolerance 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. “Pharmacodynamics, pharmacokinetics, safety and tolerability of the novel dual glucose - dependent insulinotropic 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 can potentially prevent dosing to the desired effective dose, can impair patient compliance with the treatment, and can limit the effectiveness of the treatment plan.

[0005] There is a need for a novel dosage of tildepagliflozin to provide desired glycemic control, such as demonstrated by further reduction in HbA1c and / or weight loss, while maintaining an acceptable profile of safety and adverse events. There is also a need for a novel dosing regimen of tildepagliflozin to provide desired glycemic control, such as demonstrated by further reduction in HbA1c and / or weight loss, while maintaining an acceptable profile of safety and adverse events. In addition, there is a need for options for GIP / GLP1 dual agonist therapy for conditions selected from chronic kidney disease, atherosclerosis, NAFLD, and NASH. Furthermore, there is a desire for a treatment that cures diabetes by preventing, reducing the severity of, or inducing remission of diabetes. There is a desire for a treatment that reduces or delays the progression of diabetes.

Summary of the Invention

[0006] The present invention provides a novel tirzepatide dosing regimen for use in the aforementioned therapies, comprising a maintenance dose selected from the group consisting of about 5.0 mg, about 10.0 mg, and about 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 at least about 4 weeks, and thereafter administering at least one maintenance dose approximately once a week for at least about 4 weeks. In certain embodiments, the doses may be administered for about 4 weeks. In certain embodiments, the doses may be administered for more than about 4 weeks, as determined by a nurse, patient, and / or healthcare provider. For example, the maintenance dose may be administered for more than about 4 weeks. In certain embodiments of the present invention, regardless of the presence or absence of intervening escalating doses, if additional glycemic control is required, 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 about 2.5 mg and the maintenance dose is about 5.0 mg. In another dosing regimen according to the present invention, the two escalating doses are about 2.5 mg and about 7.5 mg, and the maintenance doses are about 5.0 mg and 10.0 mg. In another aspect of the present invention, the escalating doses are about 2.5 mg, about 7.5 mg, and about 12.5 mg, and the maintenance doses are about 5.0 mg, about 10.0 mg, and about 15.0 mg. The escalating doses include about 2.5 mg, about 7.5 mg, and about 12.5 mg. The maintenance doses include about 5.0 mg, about 10.0 mg, and about 15.0 mg. The escalating dose of about 2.5 mg may be the initial or starting dose of the dosing regimen provided herein. As used herein, the terms "escalation" or "escalation dose(s)" mean the titration or titration dose described herein.

[0007] Accordingly, the present invention provides a method for treating type 2 diabetes in a patient in need thereof, comprising administering an escalating 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 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, 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 is a method for treating type 2 diabetes, wherein the escalating dose administered approximately once a week for at least about 4 weeks is about 2.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 5.0 mg. A further embodiment of the present invention is a method wherein the escalating dose administered approximately once a week for at least about 4 weeks is about 7.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 10.0 mg. A further embodiment of the present invention is a method wherein the escalating dose administered approximately once a week for at least about 4 weeks is about 12.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 15.0 mg. A further embodiment of the present invention is one wherein a second escalating dose is administered approximately once a week for at least about 4 weeks after the first maintenance dose has been administered for at least about 4 weeks, and then a second maintenance dose is administered approximately once a week for at least about 4 weeks. Accordingly, one such method comprises 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 is one wherein a third escalating dose is administered approximately once a week for at least about 4 weeks after the second maintenance dose has been administered for at least about 4 weeks, and then a third maintenance dose is administered approximately once a week for at least about 4 weeks. Accordingly, one such method comprises escalating doses of about 2.5 mg, about 7.5 mg, and about 12.5 mg, and 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, if additional blood glucose control is required, regardless of the presence or absence of intervening escalating doses, the maintenance dose can be increased to a subsequent maintenance dose. Thus, the present invention further provides a method of treating type 2 diabetes in a patient in need thereof, comprising administering an escalating 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 administering 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 optionally, thereafter, administering a second 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 optionally, thereafter, administering a third 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.

[0009] In another aspect, the present invention provides a method of treating type 2 diabetes in a patient in need thereof, comprising a) administering to the patient a dose of about 2.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks; b) increasing the dose to a dose of about 5.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, and administering to the patient approximately once a week for at least about 4 weeks; c) increasing the dose to a dose of about 7.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, and administering to the patient approximately once a week for at least about 4 weeks; d) increasing the dose to a dose of about 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, and administering to the patient approximately once a week for at least about 4 weeks; e) increasing the dose to a dose of about 12.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, and administering to the patient approximately once a week for at least about 4 weeks; f) increasing the dose to a dose of about 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, and administering to the patient approximately once a week for at least about 4 weeks.

[0010] In one aspect, the present invention is a method of treating type 2 diabetes in a patient in need thereof, comprising: a) administering to the patient a titrating dose of about 2.5 mg of tildesatide, 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 tildesatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0011] In another aspect, the present invention is a method of treating type 2 diabetes in a patient in need thereof, comprising administering to the patient a maintenance dose of about 5.0 mg of tildesatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0012] Another embodiment is a method of treating type 2 diabetes in a patient in need thereof, comprising: a) administering to the patient a maintenance dose of about 5.0 mg of tildesatide, 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 10.0 mg of tildesatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0013] Another embodiment is a method of treating type 2 diabetes in a patient in need thereof, comprising: a) administering to the patient a titrating dose of about 7.5 mg of tildesatide, 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 10.0 mg of tildesatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

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

[0015] Another embodiment is a method for treating type 2 diabetes in a patient in need thereof, a) administering to the patient a maintenance dose of about 10.0 mg of tildesatide, 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 15.0 mg of tildesatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0016] Another embodiment is a method for treating type 2 diabetes in a patient in need thereof, a) administering to the patient an escalating dose of about 12.5 mg of tildesatide, 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 15.0 mg of tildesatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

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

[0018] In another aspect, the present invention provides a method for treating type 2 diabetes in a patient in need thereof, a) administering to the patient an escalating dose of about 2.5 mg of tildesatide, 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 an escalating 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 providing a method comprising the same.

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

[0020] In another aspect, the present invention is a method for treating type 2 diabetes in a patient in need of treatment for type 2 diabetes, g) Administering to the patient an escalating 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 h) 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 i) Administering to the patient an escalating 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 j) 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 k) Administering to the patient an escalating 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 l) 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, and providing a method comprising the same.

[0021] In another aspect, the invention includes the method described in the previous paragraph, but this does not include administering escalating doses of 7.5 mg. In another aspect, the invention includes the method described in the previous paragraph, but this does not include administering escalating doses of 12.5 mg. In another aspect, the 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 glycemic control in patients in need of improved glycemic control, comprising administering at least one escalating dose approximately once a week for at least about 4 weeks, and after the escalating dose, administering at least one maintenance dose approximately once a week for at least about 4 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 tildesepatide, 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 tildesepatide, 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. Thus, one embodiment of the present invention is a method for improving glycemic control, wherein the escalating dose administered approximately once a week for at least about 4 weeks is about 2.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 5.0 mg. A further embodiment of the present invention is a method wherein the escalating dose administered approximately once a week for at least about 4 weeks is about 7.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 10.0 mg. A further embodiment of the present invention is a method wherein the escalating dose administered approximately once a week for at least about 4 weeks is about 12.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 15.0 mg. A further embodiment of the present invention is that after the first maintenance dose is administered for at least about 4 weeks, a second escalating dose is 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 is that after the second maintenance dose is administered for at least about 4 weeks, a third escalating dose is administered approximately once a week for at least about 4 weeks, and then a third 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, about 7.5 mg, and about 12.5 mg, and 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, when additional glycemic control is required, regardless of the presence or absence of intervening escalating doses, the maintenance dose can be increased to a subsequent maintenance dose. Accordingly, the present invention further provides a method of improving glycemic control in a patient in need of improved glycemic control, comprising administering an escalating dose of about 2.5 mg of tildepepide or a pharmaceutically acceptable salt thereof once approximately weekly for at least about 4 weeks, and thereafter administering a maintenance dose of about 5.0 mg of tildepepide, or a pharmaceutically acceptable salt thereof, once approximately weekly for at least about 4 weeks, and optionally, thereafter administering a second maintenance dose of about 10.0 mg of tildepepide, or a pharmaceutically acceptable salt thereof, once approximately weekly for at least about 4 weeks, and optionally, thereafter administering a third maintenance dose of about 15.0 mg of tildepepide, or a pharmaceutically acceptable salt thereof, once approximately weekly for at least about 4 weeks.

[0024] Furthermore, the present invention provides a method of improving glycemic control in a patient in need of improved glycemic control, comprising a) administering to the patient an escalating dose of about 2.5 mg of tildepepide, or a pharmaceutically acceptable salt thereof, once approximately weekly for at least about 4 weeks, and thereafter b) administering to the patient a maintenance dose of about 5.0 mg of tildepepide, or a pharmaceutically acceptable salt thereof, once approximately weekly for at least about 4 weeks.

[0025] In another aspect, the present invention provides a method of improving glycemic control in a patient in need of improved glycemic control, comprising administering to the patient a maintenance dose of about 5.0 mg of tildepepide, or a pharmaceutically acceptable salt thereof, once approximately weekly for at least about 4 weeks.

[0026] Another embodiment is a method of improving glycemic control in a patient in need of improved glycemic control, comprising a) 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 b) 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 a method.

[0027] Another embodiment is a method of improving glycemic control in a patient in need of improving glycemic control, a) Administering to the patient an escalating 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 b) 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 a method.

[0028] In another aspect, the present invention is a method of improving glycemic control in a patient in need of improving glycemic control, comprising 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 a method.

[0029] Another embodiment is a method of improving glycemic control in a patient in need of improving glycemic control, a) 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 b) 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 a method.

[0030] Another embodiment is a method of improving glycemic control in a patient in need of improving glycemic control, a) 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 b) 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 a method.

[0031] In another aspect, the present invention is a method for improving glycemic control in a patient in need thereof, comprising 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 a method.

[0032] In another aspect, the present invention is a method for improving glycemic control in a patient in need thereof, comprising 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, to provide a method. In another aspect, the present invention includes the method described in the previous paragraph, which does not include administering a gradually increasing dose of 7.5 mg.

[0033] In another aspect, the present invention is a method for improving glycemic control in a patient in need thereof, comprising a) Administering to the patient an escalating dose of about 2.5 mg of tildepazotide, 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 tildepazotide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then c) Administering to the patient an escalating dose of about 7.5 mg of tildepazotide, 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 tildepazotide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then e) Administering to the patient an escalating dose of about 12.5 mg of tildepazotide, 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 tildepazotide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method.

[0034] In another aspect, the present invention includes the method described in the previous paragraph, but this does not include administering an 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 an 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.

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

[0036] The present invention also provides a method for improving weight management in patients in need thereof, comprising administering a titration 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 titration 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, 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 titration dose is an incremental increase of 2.5 mg compared to the titration dose. Accordingly, one embodiment of the present invention is a method for improving weight management, wherein the titration dose administered approximately once a week for at least about 4 weeks is about 2.5 mg and the maintenance dose administered approximately once a week for at least about 4 weeks is about 5.0 mg. A further embodiment of the present invention is a method wherein the titration dose administered approximately once a week for at least about 4 weeks is about 7.5 mg and the maintenance dose administered approximately once a week for at least about 4 weeks is about 10.0 mg. A further embodiment of the present invention is a method wherein the titration dose administered approximately once a week for at least about 4 weeks is about 12.5 mg and the maintenance dose administered approximately once a week for at least about 4 weeks is about 15.0 mg. A further embodiment of the present invention is that after the first maintenance dose is administered for at least about 4 weeks, a second titration dose is 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 titration 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 is that after the second maintenance dose is administered for at least about 4 weeks, a third titration dose is administered approximately once a week for at least about 4 weeks, and then a third maintenance dose is administered approximately once a week for at least about 4 weeks. Thus, one such method includes titration doses of about 2.5 mg, about 7.5 mg, and about 12.5 mg, and 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, if additional glycemic control is required, with or without an intervening escalating dose, the maintenance dose may be increased to a subsequent maintenance dose. Accordingly, the present invention further provides a method of improving weight management in a patient in need thereof, comprising administering an escalating dose of about 2.5 mg of tildesatide or a pharmaceutically acceptable salt thereof once approximately weekly for at least about 4 weeks, and thereafter administering a maintenance dose of about 5.0 mg of tildesatide or a pharmaceutically acceptable salt thereof once approximately weekly for at least about 4 weeks, and optionally thereafter administering a second maintenance dose of about 10.0 mg of tildesatide or a pharmaceutically acceptable salt thereof once approximately weekly for at least about 4 weeks, and optionally thereafter administering a third maintenance dose of about 15.0 mg of tildesatide or a pharmaceutically acceptable salt thereof once approximately weekly for at least about 4 weeks.

[0038] In yet another aspect, the present invention provides a method of improving weight management in a patient in need thereof, comprising a) administering to the patient an escalating dose of about 2.5 mg of tildesatide or a pharmaceutically acceptable salt thereof once approximately weekly for at least about 4 weeks, and thereafter b) administering to the patient a maintenance dose of about 5.0 mg of tildesatide or a pharmaceutically acceptable salt thereof once approximately weekly for at least about 4 weeks.

[0039] In another aspect, the present invention provides a method of improving weight management in a patient in need thereof, comprising administering to the patient a maintenance dose of about 5.0 mg of tildesatide or a pharmaceutically acceptable salt thereof once approximately weekly for at least about 4 weeks.

[0040] Another embodiment is a method of improving weight management in a patient in need thereof, comprising a) administering to the patient a maintenance dose of about 5.0 mg of tildesatide or a pharmaceutically acceptable salt thereof once approximately weekly for at least about 4 weeks, and thereafter b) Administering to the patient a maintenance dose of approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method.

[0041] Another embodiment is a method for improving weight management in a patient in need of improving weight management, a) Administering to the patient a titrating dose of approximately 7.5 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 approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method.

[0042] In another aspect, the present invention is a method for improving weight management in a patient in need of improving weight management, comprising administering to the patient a maintenance dose of approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method.

[0043] Another embodiment is a method for improving weight management in a patient in need of improving weight management, a) Administering to the patient a maintenance dose of approximately 10.0 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 approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method.

[0044] Another embodiment is a method for improving weight management in a patient in need of improving weight management, a) Administering to the patient a titrating dose of approximately 12.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and b) Administering to the patient a maintenance dose of approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method.

[0045] In another aspect, the present invention provides a method of improving weight management in a patient in need thereof, the method comprising administering to the patient a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0046] In another aspect, the present invention provides a method of improving weight management in a patient in need thereof, a) administering to the patient a titrating dose of about 2.5 mg of tirzepatide, 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 tirzepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then c) administering to the patient a titrating dose of about 7.5 mg of tirzepatide, 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 tirzepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

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

[0048] In another aspect, the present invention provides a method of improving weight management in a patient in need thereof, a) administering to the patient a titrating dose of about 2.5 mg of tirzepatide, 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 tirzepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then c) administering to the patient a titrating dose of about 7.5 mg of tirzepatide, 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 approximately 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 an escalating dose of approximately 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 approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and providing a method comprising.

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

[0050] The present invention also provides a method for treating chronic kidney disease in a patient in need thereof, comprising administering an escalating 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 escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tildelixibat 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 tildelixibat 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 one embodiment of the present invention for the method of treating chronic kidney disease, the escalating dose administered approximately once a week for at least about 4 weeks is about 2.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 5.0 mg. A further embodiment of the present invention is a method wherein the escalating dose administered approximately once a week for at least about 4 weeks is about 7.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 10.0 mg. A further embodiment of the present invention is a method wherein the escalating dose administered approximately once a week for at least about 4 weeks is about 12.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 15.0 mg. A further embodiment of the present invention is a method wherein the escalating doses administered approximately once a week for at least about 4 weeks are about 2.5 mg and about 7.5 mg, and the maintenance doses administered approximately once a week for at least about 4 weeks are about 5.0 mg and about 10.0 mg. A further embodiment of the present invention is a method wherein the escalating doses administered approximately once a week for at least about 4 weeks are about 2.5 mg, about 5.0 mg, and about 7.5 mg, and the maintenance doses administered approximately once a week for at least about 4 weeks are about 5.0 mg, about 10.0 mg, and about 15.0 mg.

[0051] Accordingly, the present invention provides a method for treating chronic kidney disease in a patient in need thereof, comprising a) administering to the patient an escalating dose of about 2.5 mg of tildelixibat or a pharmaceutically acceptable salt thereof approximately once a week for at least about 4 weeks, and then b) administering to the patient approximately 5.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least approximately 4 weeks, to provide a method.

[0052] In another aspect, the present invention provides a method for treating chronic kidney disease in a patient in need thereof, comprising administering to the patient a maintenance dose of approximately 5.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least approximately 4 weeks.

[0053] In another embodiment, a method for treating chronic kidney disease in a patient in need thereof, comprising: a) administering to the patient a maintenance dose of approximately 5.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least approximately 4 weeks, and then b) administering to the patient approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least approximately 4 weeks, to provide a method.

[0054] In another embodiment, a method for treating chronic kidney disease in a patient in need thereof, comprising: a) administering to the patient an escalating dose of approximately 7.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least approximately 4 weeks, and then b) administering to the patient approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least approximately 4 weeks, to provide a method.

[0055] In another aspect, the present invention provides a method for treating chronic kidney disease in a patient in need thereof, comprising administering to the patient a maintenance dose of approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least approximately 4 weeks.

[0056] In another embodiment, a method for treating chronic kidney disease in a patient in need thereof, comprising: a) Administering to the patient a maintenance dose of approximately 10.0 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 approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method.

[0057] In another embodiment, a method of treating chronic kidney disease in a patient in need thereof, a) Administering to the patient an escalating dose of approximately 12.5 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 approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method.

[0058] In another aspect, the present invention is a method of treating chronic kidney disease in a patient in need thereof, comprising administering to the patient a maintenance dose of approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0059] In another aspect, the present invention is a method of treating chronic kidney disease in a patient in need thereof, a) Administering to the patient an escalating dose of approximately 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 approximately 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 an escalating dose of approximately 7.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method. d) Administering to the patient a maintenance dose of approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0060] In another aspect, the invention includes the method described in the previous paragraph, but does not include administering an escalating dose of 7.5 mg.

[0061] In another aspect, the invention is a method of treating chronic kidney disease in a patient in need thereof, a) Administering to the patient an escalating dose of approximately 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 approximately 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 an escalating dose of approximately 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 approximately 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 an escalating dose of approximately 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 approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0062] In another aspect, the invention includes the method described in the previous paragraph, but does not include administering an escalating dose of 7.5 mg. In another aspect, the invention includes the method described in the previous paragraph, but does not include administering an escalating dose of 12.5 mg. In another aspect, the invention includes the method described in the previous paragraph, but does not include administering escalating doses of 7.5 mg and 12.5 mg.

[0063] In a further embodiment, a method for treating chronic kidney disease in a patient in need thereof, comprising administering an escalating 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 escalating 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 escalating dose is an incremental increase of 2.5 mg compared to the escalating dose.

[0064] In addition, the present invention provides a method for treating atherosclerosis in a patient in need of treatment for atherosclerosis, 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. One embodiment of the present invention for a method of treating atherosclerosis is that the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 2.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 5.0 mg. A further embodiment of the present invention is a method in which the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 7.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 10.0 mg. A further embodiment of the present invention is a method in which the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 12.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 15.0 mg. A further embodiment of the present invention is a method in which the gradually increasing doses administered approximately once a week for at least about 4 weeks are about 2.5 mg and about 7.5 mg, and the maintenance doses administered approximately once a week for at least about 4 weeks are about 5.0 mg and about 10.0 mg. A further embodiment of the present invention is a method in which the gradually increasing doses administered approximately once a week for at least about 4 weeks are about 2.5 mg, about 5.0 mg, and about 7.5 mg, and the maintenance doses administered approximately once a week for at least about 4 weeks are about 5.0 mg, about 10.0 mg, and about 15.0 mg.

[0065] In a further aspect, the present invention provides a method for treating atherosclerosis in a patient in need of treatment for atherosclerosis, comprising 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 approximately 5.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

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

[0067] Another embodiment is a method for treating atherosclerosis in a patient in need thereof, a) Administering to the patient a maintenance dose of approximately 5.0 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 approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0068] Another embodiment is a method for treating atherosclerosis in a patient in need thereof, a) Administering to the patient an escalating dose of approximately 7.5 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 approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0069] In another aspect, the present invention provides a method for treating atherosclerosis in a patient in need thereof, comprising administering to the patient a maintenance dose of approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0070] Another embodiment is a method of treating atherosclerosis in a patient in need of treatment for atherosclerosis, comprising: a) 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 b) administering to the patient about 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0071] Another embodiment is a method of treating atherosclerosis in a patient in need of treatment for atherosclerosis, comprising: a) administering to the patient an escalating 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 b) administering to the patient about 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0072] In another aspect, the invention is a method of treating atherosclerosis in a patient in need of treatment for atherosclerosis, comprising: a) administering to the patient an escalating 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 an escalating 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.

[0073] In another aspect, the invention includes the method described in the previous paragraph, but this does not include administering a escalating dose of 7.5 mg.

[0074] In another aspect, the invention is a method of treating atherosclerosis in a patient in need thereof, comprising: a) administering to the patient an escalating 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 an escalating 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 an escalating 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.

[0075] In another aspect, the invention includes the method described in the previous paragraph, but this does not include administering an escalating dose of 7.5 mg. In another aspect, the invention includes the method described in the previous paragraph, but this does not include administering an escalating dose of 12.5 mg. In another aspect, the 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.

[0076] In addition, the present invention provides a method for treating non-alcoholic fatty liver disease (NAFLD) in a patient in need thereof, 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, 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 increment of 2.5 mg compared to the gradually increasing dose. One embodiment of the present invention for a method of treating NAFLD is that the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 2.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 5.0 mg. A further embodiment of the present invention is a method wherein the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 7.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 10.0 mg. A further embodiment of the present invention is a method wherein the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 12.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 15.0 mg. A further embodiment of the present invention is a method wherein the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 2.5 mg and about 7.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 5.0 mg and about 10.0 mg. A further embodiment of the present invention is a method wherein the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 2.5 mg, about 5.0 mg, and about 7.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 5.0 mg, about 10.0 mg, and about 15.0 mg.

[0077] Accordingly, the present invention provides a method for treating non-alcoholic fatty liver disease (NAFLD) in a patient in need thereof, 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 approximately 15.0 mg of cilzepatiide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks,

[0078] In another aspect, the present invention provides a method for treating NAFLD in a patient in need thereof, comprising administering to the patient a maintenance dose of approximately 5.0 mg of cilzepatiide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks.

[0079] Another embodiment is a method for treating NAFLD in a patient in need thereof, a) administering to the patient a maintenance dose of approximately 5.0 mg of cilzepatiide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks, and then b) administering to the patient approximately 10.0 mg of cilzepatiide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks.

[0080] Another embodiment is a method for treating NAFLD in a patient in need thereof, a) administering to the patient an escalating dose of approximately 7.5 mg of cilzepatiide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks, and then b) administering to the patient approximately 10.0 mg of cilzepatiide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks.

[0081] In another aspect, the present invention provides a method for treating NAFLD in a patient in need thereof, comprising administering to the patient a maintenance dose of approximately 10.0 mg of cilzepatiide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks.

[0082] Another embodiment is a method for treating NAFLD in a patient in need thereof, a) Administering to the patient a maintenance dose of approximately 10.0 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 approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method.

[0083] Another embodiment is a method of treating NAFLD in a patient in need of treatment for NAFLD, a) Administering to the patient an escalating dose of approximately 12.5 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 approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method.

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

[0085] In another aspect, the present invention is a method of treating NAFLD in a patient in need of treatment for NAFLD, a) Administering to the patient an escalating dose of approximately 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 approximately 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 an escalating dose of approximately 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 approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method.

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

[0087] In another aspect, the present invention is a method of treating non-alcoholic fatty liver disease (NAFLD) in a patient in need thereof, 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 a maintenance dose of about 5.0 mg of tildesepatide, 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 tildesepatide, 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 tildesepatide, 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 tildesepatide, 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 tildesepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and providing a method comprising.

[0088] In another aspect, the present invention includes the method described in the previous paragraph, but this does not include administering a gradually increasing 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 gradually increasing 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 gradually increasing doses of 7.5 mg and 12.5 mg.

[0089] In one embodiment, a method for treating dyslipidemia in a patient in need thereof, comprising administering an escalating 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 escalating 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, 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 escalating dose is an incremental increase of 2.5 mg compared to the escalating dose.

[0090] The present invention also provides a method for treating NASH in a patient in need thereof, 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, 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 the gradually increasing dose. One embodiment of the present invention for the method of treating NASH is that the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 2.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 5.0 mg. A further embodiment of the present invention is a method wherein the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 7.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 10.0 mg. A further embodiment of the present invention is a method wherein the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 12.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 15.0 mg. A further embodiment of the present invention is a method wherein the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 2.5 mg and about 7.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 5.0 mg and about 10.0 mg. A further embodiment of the present invention is a method wherein the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 2.5 mg, about 5.0 mg, and about 7.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 5.0 mg, about 10.0 mg, and about 15.0 mg.

[0091] Accordingly, the present invention provides a method for treating NASH in a patient in need thereof, 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 approximately 5.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks, and providing a method comprising the steps.

[0092] In another aspect, the present invention provides a method for treating NASH in a patient in need thereof, comprising administering to the patient a maintenance dose of approximately 5.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks.

[0093] Another embodiment is a method for treating NASH in a patient in need thereof, comprising: a) administering to the patient a maintenance dose of approximately 5.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks, and then b) administering to the patient approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks, and providing a method comprising the steps.

[0094] Another embodiment is a method for treating NASH in a patient in need thereof, comprising: a) administering to the patient an escalating dose of approximately 7.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks, and then b) administering to the patient approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks, and providing a method comprising the steps.

[0095] In another aspect, the present invention provides a method for treating NASH in a patient in need thereof, comprising administering to the patient a maintenance dose of approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks.

[0096] Another embodiment is a method for treating NASH in a patient in need thereof, comprising: a) Administering to the patient a maintenance dose of approximately 10.0 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 approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method.

[0097] Another embodiment is a method of treating NASH in a patient in need thereof, a) Administering to the patient an escalating dose of approximately 12.5 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 approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method.

[0098] In another aspect, the present invention is a method of treating NASH in a patient in need thereof, comprising administering to the patient a maintenance dose of approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0099] In another aspect, the present invention is a method of treating NASH in a patient in need thereof, a) Administering to the patient an escalating dose of approximately 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 approximately 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 an escalating dose of approximately 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 approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method.

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

[0101] In another aspect, the present invention is a method of treating NASH in a patient in need of treatment for NASH, a) administering to the patient a titrating 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 a maintenance dose of about 5.0 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then c) administering to the patient a titrating dose of about 7.5 mg of tildesepatide, 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 tildesepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then e) administering to the patient a titrating dose of about 12.5 mg of tildesepatide, 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 tildesepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and provides a method comprising.

[0102] In another aspect, the present invention includes the method described in the previous paragraph, but this does not include administering a titrating 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 titrating 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 titrating doses of 7.5 mg and 12.5 mg.

[0103] Also, the present invention provides a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, 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, 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 the gradually increasing dose. One embodiment of the present invention for a method of curing diabetes, inducing remission or regression of diabetes, or preventing diabetes is that the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 2.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 5.0 mg. A further embodiment of the present invention is a method wherein the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 7.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 10.0 mg. A further embodiment of the present invention is a method wherein the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 12.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 15.0 mg. A further embodiment of the present invention is a method wherein the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 2.5 mg and about 7.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 5.0 mg and about 10.0 mg. A further embodiment of the present invention is a method wherein the gradually increasing dose administered approximately once a week for at least about 4 weeks is about 2.5 mg, about 5.0 mg, and about 7.5 mg, and the maintenance dose administered approximately once a week for at least about 4 weeks is about 5.0 mg, about 10.0 mg, and about 15.0 mg.

[0104] Accordingly, the present invention is a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, comprising: a) administering to the patient a gradually increasing dose of about 2.5 mg of tildepagliflozin, 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 tildepagliflozin, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0105] In another aspect, the present invention is a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, comprising administering to the patient a maintenance dose of about 5.0 mg of tildepagliflozin, or a pharmaceutically acceptable salt thereof, approximately 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 in need thereof, comprising: a) administering to the patient a maintenance dose of about 5.0 mg of tildepagliflozin, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then b) administering to the patient about 10.0 mg of tildepagliflozin, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0107] Another embodiment is a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, comprising: a) Administering to the patient an escalating 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 b) Administering to the patient about 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method.

[0108] In another aspect, the present invention is a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, the method comprising 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.

[0109] Another embodiment is a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, a) 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 b) Administering to the patient about 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method.

[0110] Another embodiment is a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, a) Administering to the patient an escalating 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 b) Administering to the patient about 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide a method.

[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 in need thereof, the method comprising 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.

[0112] In another aspect, the present invention provides a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, a) administering to the patient a titrating 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 titrating 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.

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

[0114] In another aspect, the present invention provides a method for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, a) administering to the patient a titrating 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 an escalating 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 an escalating 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, and providing a method comprising the same.

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

[0116] Furthermore, the present invention provides the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating type 2 diabetes in a patient in need thereof, comprising administering an escalating 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 escalating 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, 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 tildepazide, 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.

[0117] The present invention relates to a medicament for treating type 2 diabetes in patients in need thereof, 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, and provides the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament comprising the same.

[0118] In another aspect, the present invention relates to a medicament for treating type 2 diabetes in patients in need thereof, which comprises 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 provides the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament comprising the same.

[0119] Another embodiment relates to a medicament for treating type 2 diabetes in patients in need thereof, a) 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 b) administering to the patient about 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and provides the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament comprising the same.

[0120] Another embodiment relates to a medicament for treating type 2 diabetes in patients in need thereof, a) 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 b) administering to the patient approximately once a week for at least about 4 weeks approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, to provide the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0121] In another aspect, the present invention provides a medicament for treating type 2 diabetes in a patient in need thereof, which comprises administering to the patient approximately once a week for at least about 4 weeks a maintenance dose of approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, to provide the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0122] Another embodiment is a medicament for treating type 2 diabetes in a patient in need thereof, a) administering to the patient approximately once a week for at least about 4 weeks a maintenance dose of approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, and then b) administering to the patient approximately once a week for at least about 4 weeks approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, to provide the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0123] Another embodiment is a medicament for treating type 2 diabetes in a patient in need thereof, a) administering to the patient approximately once a week for at least about 4 weeks an escalating dose of approximately 12.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, and then b) administering to the patient approximately once a week for at least about 4 weeks approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, to provide the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0124] In another aspect, the present invention provides a use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating type 2 diabetes in a patient in need thereof, comprising 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.

[0125] In another aspect, the present invention provides a medicament for treating type 2 diabetes in a patient in need thereof, a) administering to the patient a titrating 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 titrating 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 provides a use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0126] In another aspect, the present invention provides a medicament comprising the medicament described in the previous paragraph, which does not include administering a titrating dose of 7.5 mg.

[0127] In another aspect, the present invention provides a medicament for treating type 2 diabetes in a patient in need thereof, a) administering to the patient a titrating 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 an escalating 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 an escalating 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, and providing the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament comprising the same.

[0128] In another aspect, the present invention includes the medicament described in the previous paragraph, which does not include administering an escalating dose of 7.5 mg. In another aspect, the present invention includes the medicament described in the previous paragraph, which does not include administering an escalating dose of 12.5 mg. In another aspect, the present invention includes the medicament described in the previous paragraph, which does not include administering escalating doses of 7.5 mg and 12.5 mg.

[0129] Furthermore, the present invention provides the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving blood glucose control in a patient in need of improving blood glucose control, comprising administering an escalating 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 escalating 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, 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 tildepazide, 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.

[0130] Furthermore, the present invention provides a medicament for improving blood glucose control in a patient in need of improving blood glucose control, comprising: a) administering to the patient an escalating 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, for use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0131] In another aspect, the present invention provides a medicament for improving blood glucose control in a patient in need of improving blood glucose control, comprising 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, for use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0132] Another embodiment is a medicament for improving blood glucose control in a patient in need of improving blood glucose control, comprising: a) administering to the patient an escalating 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 b) administering to the patient about 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, for use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0133] Another embodiment is a medicament for improving blood glucose control in a patient in need of improving blood glucose control, comprising: a) administering to the patient an escalating 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 b) administering to the patient approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and providing the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0134] In another aspect, the present invention provides a medicament for improving glycemic control in a patient in need thereof, comprising administering to the patient a maintenance dose of approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and providing the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0135] Another embodiment is a medicament for improving glycemic control in a patient in need thereof, a) administering to the patient a maintenance dose of approximately 10.0 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 approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and providing the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0136] Another embodiment is a medicament for improving glycemic control in a patient in need thereof, a) administering to the patient an escalating dose of approximately 12.5 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 approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and providing the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0137] In another aspect, the present invention provides a use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving glycemic control in a patient in need of improving glycemic control, comprising 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.

[0138] In another aspect, the present invention provides a medicament for improving glycemic control in a patient in need of improving glycemic control, a) administering to the patient a titrating 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 titrating 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 provides a use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0139] In another aspect, the present invention provides a medicament comprising the medicament described in the previous paragraph, which does not include administering a titrating dose of 7.5 mg.

[0140] In another aspect, the present invention provides a medicament for improving glycemic control in a patient in need of improving glycemic control, a) administering to the patient a titrating 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 tirlizepatide, 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 tirlizepatide, 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 tirlizepatide, 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 tirlizepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide the use of tirlizepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament comprising the same.

[0141] 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. In another aspect, the present invention includes the medicament described in the previous paragraph, which does not include administering a gradually increasing dose of 12.5 mg. In another aspect, the present invention includes the medicament described in the previous paragraph, which does not include administering gradually increasing doses of 7.5 mg and 12.5 mg.

[0142] Furthermore, the present invention provides a medicament for improving weight management in a patient in need of improving weight management, 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 tirlizepatide, 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 tirlizepatide, 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, to provide the use of tirlizepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0143] In yet another aspect, the present invention is a medicament for improving weight management in a patient in need thereof, comprising: a) administering to the patient a titrated dose of about 2.5 mg of tirzepatide, 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 tirzepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and provides for the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0144] In another aspect, the present invention is a medicament for improving weight management in a patient in need thereof, comprising administering to the patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and provides for the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0145] Another embodiment is a medicament for improving weight management in a patient in need thereof, comprising: a) administering to the patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then b) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and provides for the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0146] Another embodiment is a medicament for improving weight management in a patient in need thereof, comprising: a) administering to the patient a titrated dose of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then b) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and provides for the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0147] In another aspect, the present invention provides a use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving weight management in a patient in need of improving weight management, comprising 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.

[0148] Another embodiment is a medicament for improving weight management in a patient in need of improving weight management, a) 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 b) administering to the patient about 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, in the manufacture of a medicament, provides a use of tildepazide, or a pharmaceutically acceptable salt thereof.

[0149] Another embodiment is a medicament for improving weight management in a patient in need of improving weight management, a) administering to the patient an escalating 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 b) administering to the patient about 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, in the manufacture of a medicament, provides a use of tildepazide, or a pharmaceutically acceptable salt thereof.

[0150] In another aspect, the present invention provides a use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving weight management in a patient in need of improving weight management, comprising 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.

[0151] In another aspect, the present invention is a medicament for improving weight management in a patient in need of such improvement, comprising: a) administering to the patient an escalating 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 an escalating 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 provides for the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0152] In another aspect, the present invention is a medicament comprising the medicament described in the previous paragraph, which does not include administering an escalating dose of 7.5 mg.

[0153] In another aspect, the present invention is a medicament for improving weight management in a patient in need of such improvement, comprising: a) administering to the patient an escalating 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 an escalating 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 an escalating 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.

[0154] In another aspect, the present invention includes the medicament described in the previous paragraph, but does not include administering an escalating dose of 7.5 mg. In another aspect, the present invention includes the medicament described in the previous paragraph, but does not include administering an escalating dose of 12.5 mg. In another aspect, the present invention includes the medicament described in the previous paragraph, but does not include administering escalating doses of 7.5 mg and 12.5 mg.

[0155] Furthermore, the present invention provides the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating chronic kidney disease in a patient in need thereof, comprising administering an escalating 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 escalating 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, 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 tildepazide, 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.

[0156] The present invention is a medicament for treating chronic kidney disease in a patient in need thereof, a) administering to the patient an escalating 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 approximately 5.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least about 4 weeks, in the manufacture of a medicament, providing the use of tildepazide, or a pharmaceutically acceptable salt thereof.

[0157] In another aspect, the present invention provides a medicament for treating chronic kidney disease in a patient in need thereof, comprising administering to the patient a maintenance dose of approximately 5.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, in the manufacture of a medicament, providing the use of tildepazide, or a pharmaceutically acceptable salt thereof.

[0158] Another embodiment is a medicament for treating chronic kidney disease in a patient in need thereof, a) administering to the patient a maintenance dose of approximately 5.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then b) administering approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least about 4 weeks, in the manufacture of a medicament, providing the use of tildepazide, or a pharmaceutically acceptable salt thereof.

[0159] Another embodiment is a medicament for treating chronic kidney disease in a patient in need thereof, a) administering to the patient a gradually increasing dose of approximately 7.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then b) administering approximately 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, to the patient approximately once a week for at least about 4 weeks, in the manufacture of a medicament, providing the use of tildepazide, or a pharmaceutically acceptable salt thereof.

[0160] In another aspect, the present invention provides the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating chronic kidney disease in a patient in need thereof, comprising 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.

[0161] Another embodiment is a medicament for treating chronic kidney disease in a patient in need thereof, a) 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 b) administering to the patient about 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, in the manufacture of a medicament, providing the use of tildepazide, or a pharmaceutically acceptable salt thereof.

[0162] Another embodiment is a medicament for treating chronic kidney disease in a patient in need thereof, a) administering to the patient an escalating 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 b) administering to the patient about 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, in the manufacture of a medicament, providing the use of tildepazide, or a pharmaceutically acceptable salt thereof.

[0163] In another aspect, the present invention provides the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating chronic kidney disease in a patient in need thereof, comprising 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.

[0164] In another aspect, the present invention is a medicament for treating chronic kidney disease in a patient in need thereof, comprising: a) administering to the patient a titrated dose of about 2.5 mg of tildelixibat, 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 tildelixibat, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then c) administering to the patient a titrated dose of about 7.5 mg of tildelixibat, 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 tildelixibat, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and provides the use of tildelixibat, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0165] In another aspect, the present invention comprises the medicament described in the previous paragraph, which does not include administering a titrated dose of 7.5 mg.

[0166] In another aspect, the present invention is a medicament for treating chronic kidney disease in a patient in need thereof, comprising: a) administering to the patient a titrated dose of about 2.5 mg of tildelixibat, 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 tildelixibat, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then c) administering to the patient a titrated dose of about 7.5 mg of tildelixibat, 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 tildelixibat, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then e) administering to the patient an escalating 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, in the manufacture of a medicament, provides the use of tildepazide, or a pharmaceutically acceptable salt thereof.

[0167] In another aspect, the invention includes the medicament described in the previous paragraph, which does not include administering an escalating dose of 7.5 mg. In another aspect, the invention includes the medicament described in the previous paragraph, which does not include administering an escalating dose of 12.5 mg. In another aspect, the invention includes the medicament described in the previous paragraph, which does not include administering escalating doses of 7.5 mg and 12.5 mg.

[0168] In a further embodiment, the invention provides a medicament for treating diabetic nephropathy in a patient in need thereof, comprising administering an escalating 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 escalating 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, 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 tildepazide, 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 the manufacture of a medicament, provides the use of tildepazide, or a pharmaceutically acceptable salt thereof.

[0169] Furthermore, the present invention provides the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating atherosclerosis in a patient in need thereof, comprising administering a titration 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 titration 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, 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 tildepazide, or a pharmaceutically acceptable salt thereof, and the maintenance dose after the titration dose is an incremental increase of 2.5 mg compared to the titration dose.

[0170] Furthermore, the present invention provides a medicament for treating atherosclerosis in a patient in need thereof, a) administering to the patient an incremental 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, in the manufacture of a medicament.

[0171] In another aspect, the present invention provides the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating atherosclerosis in a patient in need thereof, comprising 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.

[0172] Another embodiment is a medicament for treating atherosclerosis in a patient in need thereof, a) Administer 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 b) Provide the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament, comprising administering to the patient about 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0173] Another embodiment is a medicament for treating atherosclerosis in a patient in need thereof, a) Administer to the patient an escalating 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 b) Provide the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament, comprising administering to the patient about 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0174] In another aspect, the present invention is a medicament for treating atherosclerosis in a patient in need thereof, and provides the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament, comprising 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.

[0175] Another embodiment is a medicament for treating atherosclerosis in a patient in need thereof, a) Administer 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 b) Provide the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament, comprising administering to the patient about 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0176] Another embodiment is a medicament for treating atherosclerosis in a patient in need of treatment for atherosclerosis, a) administering to the patient an escalating dose of about 12.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, b) administering to the patient about 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and provides the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0177] In another aspect, the present invention is a medicament for treating atherosclerosis in a patient in need of treatment for atherosclerosis, which comprises 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, and provides the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0178] In another aspect, the present invention is a medicament for treating atherosclerosis in a patient in need of treatment for atherosclerosis, a) administering to the patient an escalating 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 an escalating 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 provides the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0179] In another aspect, the invention comprises the agent described in the previous paragraph, but does not include administering a titrated dose of 7.5 mg.

[0180] In another aspect, the invention is an agent for treating atherosclerosis in a patient in need thereof, comprising: a) administering to the patient a titrated 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 titrated 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 titrated 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, and provides for the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of an agent.

[0181] In another aspect, the invention comprises the agent described in the previous paragraph, but does not include administering a titrated dose of 7.5 mg. In another aspect, the invention comprises the agent described in the previous paragraph, but does not include administering a titrated dose of 12.5 mg. In another aspect, the invention comprises the agent described in the previous paragraph, but does not include administering titrated doses of 7.5 mg and 12.5 mg.

[0182] In one embodiment, a method for treating dyslipidemia in a patient in need of treatment for dyslipidemia, comprising administering a gradually 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 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.

[0183] In one embodiment, a method for treating dyslipidemia in a patient in need of treatment for dyslipidemia, comprising administering at least one gradually increasing dose approximately once a week for at least about four weeks, and after the gradually increasing dose, administering at least one maintenance dose approximately once a week for at least about four 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, 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 increment of 2.5 mg.

[0184] In one embodiment, a method for treating dyslipidemia, wherein the gradually increasing dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

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

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

[0187] In one embodiment, a method for treating dyslipidemia, further comprising a gradually 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 a titration dose of about 12.5 mg and a maintenance dose of about 15.0 mg.

[0189] In one embodiment, a method for treating dyslipidemia, wherein the patient in need of such treatment does not have co-existing type 1 or type 2 diabetes.

[0190] Furthermore, the present invention provides a use of tildesatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NALFD in a patient in need of such treatment, comprising administering a titration 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 titration dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tildesatide, 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 tildesatide, or a pharmaceutically acceptable salt thereof, and the maintenance dose after the titration dose is an incremental increase of 2.5 mg compared to the titration dose.

[0191] In another aspect, the present invention provides a use of tildesatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NAFLD in a patient in need of such treatment, a) administering to the patient a titration dose of about 2.5 mg of tildesatide, 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 tildesatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0192] In another aspect, the present invention provides the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NAFLD in a patient in need thereof, comprising 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.

[0193] Another embodiment is a medicament for treating NAFLD in a patient in need thereof, a) 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 b) administering to the patient about 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, in the manufacture of a medicament, providing the use of tildepazide, or a pharmaceutically acceptable salt thereof.

[0194] Another embodiment is a medicament for treating NAFLD in a patient in need thereof, a) administering to the patient an escalating 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 b) administering to the patient about 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, in the manufacture of a medicament, providing the use of tildepazide, or a pharmaceutically acceptable salt thereof.

[0195] In another aspect, the present invention provides the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NAFLD in a patient in need thereof, comprising 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.

[0196] Another embodiment is a medicament for treating NAFLD in a patient in need thereof, a) administering to the patient a maintenance dose of about 10.0 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 15.0 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and provides a method comprising.

[0197] Another embodiment is a medicament for treating NAFLD in a patient in need thereof, a) administering to the patient a titrating dose of about 12.5 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 15.0 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and provides the use of tildesepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament comprising.

[0198] In another aspect, the present invention is a medicament for treating NAFLD in a patient in need thereof, and provides the use of tildesepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament comprising administering to the patient a maintenance dose of about 15.0 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0199] In another aspect, the present invention is a medicament for treating NAFLD in a patient in need thereof, a) administering to the patient a titrating 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 a maintenance dose of about 5.0 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then c) administering to the patient, approximately once a week for at least about 4 weeks, an escalating dose of about 7.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, and then d) administering to the patient, approximately once a week for at least about 4 weeks, a maintenance dose of about 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, 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 comprises the medicament described in the previous paragraph, which does not include administering an escalating dose of 7.5 mg.

[0201] In another aspect, the present invention is a medicament for treating NAFLD in a patient in need of treatment for NAFLD, a) administering to the patient, approximately once a week for at least about 4 weeks, an escalating dose of about 2.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, and then b) administering to the patient, approximately once a week for at least about 4 weeks, a maintenance dose of about 5.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, and then c) administering to the patient, approximately once a week for at least about 4 weeks, an escalating dose of about 7.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, and then d) administering to the patient, approximately once a week for at least about 4 weeks, a maintenance dose of about 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, and then e) administering to the patient, approximately once a week for at least about 4 weeks, an escalating dose of about 12.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, and then f) administering to the patient, approximately once a week for at least about 4 weeks, a maintenance dose of about 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, 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 comprises the agent described in the previous paragraph, but does not include administering a titrating dose of 7.5 mg. In another aspect, the present invention comprises the agent described in the previous paragraph, but does not include administering a titrating dose of 12.5 mg. In another aspect, the present invention comprises the agent described in the previous paragraph, but does not include administering titrating doses of 7.5 mg and 12.5 mg.

[0203] Furthermore, the present invention provides for the use of tildesepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NASH in a patient in need thereof, comprising administering a titrating 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 titrating 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 titrating dose is an incremental increase of 2.5 mg compared to the titrating dose.

[0204] Furthermore, the present invention provides for the use of tildesepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NASH in a patient in need thereof, a) administering to the patient a titrating 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 a use of tildesepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NASH in a patient in need thereof, comprising administering to the patient a maintenance dose of about 5.0 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0206] Another embodiment is a medicament for treating NASH in a patient in need thereof, a) administering to the patient a maintenance dose of about 5.0 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 10.0 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, in the manufacture of a medicament, providing a use of tildesepatide, or a pharmaceutically acceptable salt thereof.

[0207] Another embodiment is a medicament for treating NASH in a patient in need thereof, a) administering to the patient an escalating dose of about 7.5 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 10.0 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, providing a method.

[0208] In another aspect, the present invention provides a use of tildesepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NASH in a patient in need thereof, comprising administering to the patient a maintenance dose of about 10.0 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0209] Another embodiment is a medicament for treating NASH in a patient in need thereof, a) Administering to the patient a maintenance dose of approximately 10.0 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 approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide for the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0210] Another embodiment is a medicament for treating NASH in a patient in need thereof, a) Administering to the patient an escalating dose of approximately 12.5 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 approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide for the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0211] In another aspect, the present invention is a medicament for treating NASH in a patient in need thereof, comprising administering to the patient a maintenance dose of approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, to provide for the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0212] In another aspect, the present invention is a medicament for treating NASH, a) Administering to the patient an escalating dose of approximately 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 approximately 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 an escalating dose of approximately 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, approximately once a week for at least about 4 weeks, a maintenance dose of about 10.0 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, to provide the use of tildesepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0213] In another aspect, the present invention includes the medicament described in the previous paragraph, which does not include administering a escalating dose of 7.5 mg.

[0214] In another aspect, the present invention is a medicament for treating NASH in a patient in need of treatment for NASH, a) administering to the patient, approximately once a week for at least about 4 weeks, an escalating dose of about 2.5 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, and then b) administering to the patient, approximately once a week for at least about 4 weeks, a maintenance dose of about 5.0 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, and then c) administering to the patient, approximately once a week for at least about 4 weeks, an escalating dose of about 7.5 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, and then d) administering to the patient, approximately once a week for at least about 4 weeks, a maintenance dose of about 10.0 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, and then e) administering to the patient, approximately once a week for at least about 4 weeks, an escalating dose of about 12.5 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, and then f) administering to the patient, approximately once a week for at least about 4 weeks, a maintenance dose of about 15.0 mg of tildesepatide, or a pharmaceutically acceptable salt thereof, to provide the use of tildesepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[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 for the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, 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, 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 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 for the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, 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 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 in need thereof, comprising 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.

[0219] Another embodiment is a medicament for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, a) 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 b) administering to the patient about 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and provides a use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of the medicament.

[0220] Another embodiment is a medicament for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, a) administering to the patient an escalating 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 b) administering to the patient about 10.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and provides a use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of the medicament.

[0221] In another aspect, the present invention provides a method for manufacturing a medicament for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, the method comprising administering to the patient a maintenance dose of about 10.0 mg of tildepazide or a pharmaceutically acceptable salt thereof once approximately per week for at least about 4 weeks, the use of tildepazide or a pharmaceutically acceptable salt thereof in the manufacture of the medicament.

[0222] Another embodiment provides a medicament for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, a) administering to the patient a maintenance dose of about 10.0 mg of tildepazide or a pharmaceutically acceptable salt thereof once approximately per week for at least about 4 weeks, and then b) administering to the patient about 15.0 mg of tildepazide or a pharmaceutically acceptable salt thereof once approximately per week for at least about 4 weeks, the use of tildepazide or a pharmaceutically acceptable salt thereof in the manufacture of the medicament.

[0223] Another embodiment provides a medicament for curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, a) administering to the patient an increasing dose of about 12.5 mg of tildepazide or a pharmaceutically acceptable salt thereof once approximately per week for at least about 4 weeks, and then b) administering to the patient about 15.0 mg of tildepazide or a pharmaceutically acceptable salt thereof once approximately per week for at least about 4 weeks, the use of tildepazide or a pharmaceutically acceptable salt thereof in the manufacture of the medicament.

[0224] In another aspect, the present invention provides a method for treating diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, the method comprising administering to the patient a maintenance dose of about 15.0 mg of tildepagliflozin, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks, for use in the manufacture of a medicament.

[0225] In another aspect, the present invention provides a method for treating diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, the method comprising: a) administering to the patient a gradually increasing dose of about 2.5 mg of tildepagliflozin, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks, and then b) administering to the patient a maintenance dose of about 5.0 mg of tildepagliflozin, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks, and then c) administering to the patient a gradually increasing dose of about 7.5 mg of tildepagliflozin, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks, and then d) administering to the patient a maintenance dose of about 10.0 mg of tildepagliflozin, or a pharmaceutically acceptable salt thereof, once approximately per week for at least about 4 weeks, for use in the manufacture of a medicament.

[0226] In another aspect, the present invention provides a medicament as described in the previous paragraph, which does not include administering a gradually increasing dose of 7.5 mg.

[0227] In another aspect, the present invention provides a method for treating diabetes, inducing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, the method comprising: a) Administering to the patient an escalating dose of approximately 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 approximately 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 an escalating dose of approximately 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 approximately 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 an escalating dose of approximately 12.5 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks, and then f) Providing the use of tildepazide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament, comprising: administering to the patient a maintenance dose of approximately 15.0 mg of tildepazide, or a pharmaceutically acceptable salt thereof, approximately once a week for at least about 4 weeks.

[0228] In another aspect, the present invention comprises the medicament described in the previous paragraph, which does not include administering an escalating dose of 7.5 mg. In another aspect, the present invention comprises the medicament described in the previous paragraph, which does not include administering an escalating dose of 12.5 mg. In another aspect, the present invention comprises the medicament described in the previous paragraph, which does not include administering escalating doses of 7.5 mg and 12.5 mg.

[0229] One embodiment of the invention regarding the use in the manufacture of the above agent is that the escalating dose administered once a week for 4 weeks is about 2.5 mg, and the maintenance dose administered once a week for 4 weeks is about 5.0 mg. A further embodiment of the invention is that the escalating dose administered once a week for 4 weeks is about 7.5 mg, and the maintenance dose administered once a week for 4 weeks is about 10.0 mg. A further embodiment of the invention is that the escalating dose administered once a week for 4 weeks is about 12.5 mg, and the maintenance dose administered once a week for 4 weeks is about 15.0 mg. A further embodiment of the invention is that the escalating doses administered once a week for 4 weeks are about 2.5 mg and about 7.5 mg, and the maintenance doses administered once a week for 4 weeks are about 5.0 mg and about 10.0 mg. A further embodiment of the invention is that the escalating doses administered once a week for 4 weeks are about 2.5 mg, about 5.0 mg and about 7.5 mg, and the maintenance doses administered once a week for 4 weeks are about 5.0 mg, about 10.0 mg and about 15.0 mg.

[0230] In Embodiment 1a, an agent for preventing diabetes in a patient in need of diabetes prevention, comprising administering an escalating dose approximately once a week for at least about 2 weeks, and then administering a maintenance dose approximately once a week for at least about 2 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 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 escalating dose is an incremental increase of 2.5 mg compared to the escalating dose, is the use of tildesepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of an agent.

[0231] In Embodiment 2a, a medicament for preventing diabetes in a patient in need of diabetes prevention, comprising administering an escalating 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 escalating 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 escalating dose is an incremental increase of 5.0 mg compared to the escalating dose, use of tildesepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

[0232] In Embodiment 3a, it is the use of Embodiment 1a or 2a, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

[0233] In Embodiment 4a, it is the use of Embodiment 1a or 2a, wherein the escalating dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

[0234] In Embodiment 5a, it is the use of Embodiment 1a or 2a, wherein the escalating dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

[0235] In Embodiment 6a, it is the use of Embodiment 3a, further comprising an escalating dose of about 7.5 mg and a maintenance dose of about 10.0 mg.

[0236] In Embodiment 7a, it is the use of Embodiment 6a and further includes a titration dose of about 12.5 mg and a maintenance dose of about 15.0 mg. In Embodiment 8a, a medicament for treating chronic kidney disease in a patient in need thereof, comprising administering a titration dose approximately once a week for at least about 2 weeks, and then administering a maintenance dose approximately once a week for at least about 2 weeks, wherein the titration 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, 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 titration dose is an incremental increase of 2.5 mg compared to the titration dose, which is the use of tildesepatide or a pharmaceutically acceptable salt thereof in the manufacture of a medicament.

[0237] In Embodiment 9a, a medicament for treating chronic kidney disease in a patient in need thereof, comprising administering at least one titration dose approximately once a week for at least about 4 weeks, and after the titration dose, administering at least one maintenance dose approximately once a week for at least about 4 weeks, wherein the titration 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, 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 titration dose is an incremental increase of 5.0 mg compared to the titration dose, which is the use of tildesepatide or a pharmaceutically acceptable salt thereof in the manufacture of a medicament.

[0238] In Embodiment 10a, it is the use of Embodiment 8a or 9a, the titration dose is about 2.5 mg, and the maintenance dose is about 5.0 mg.

[0239] In Embodiment 11a, it is the use of Embodiment 8a or 9a, the titration dose is about 7.5 mg, and the maintenance dose is about 10.0 mg.

[0240] In Embodiment 12a, it is the use of Embodiment 8a or 9a, the escalating dose is about 12.5 mg, and the maintenance dose is about 15.0 mg.

[0241] In Embodiment 13a, it is the use of Embodiment 10a, and further includes an escalating dose of about 7.5 mg and a maintenance dose of about 10.0 mg.

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

[0243] In another aspect, the present invention provides tildepagliflozin, or a pharmaceutically acceptable salt thereof, for use in treating type 2 diabetes. In one embodiment, the present invention provides tildepagliflozin, or a pharmaceutically acceptable salt thereof, for use in treating type 2 diabetes in a patient in need thereof, wherein the escalating dose is administered approximately once a week for at least about 4 weeks, and thereafter the maintenance dose is administered approximately once a week for at least about 4 weeks, the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tildepagliflozin, 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 tildepagliflozin, 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 aspect, the present invention provides tildepagliflozin, or a pharmaceutically acceptable salt thereof, for use in improving glycemic control. In another aspect, the present invention provides tildepagliflozin, or a pharmaceutically acceptable salt thereof, for use in improving glycemic control in a patient in need thereof, wherein the escalating dose is administered approximately once a week for at least about 4 weeks, and thereafter the maintenance dose is administered approximately once a week for at least about 4 weeks, the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tildepagliflozin, 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 tildepagliflozin, 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 aspect, the present invention provides tildepagliflozin, or a pharmaceutically acceptable salt thereof, for use in improving weight management.In another aspect, the present invention provides tildepazotide, or a pharmaceutically acceptable salt thereof, for use in improving the weight management of patients in need of improved weight management, wherein the escalating dose is administered approximately once a week for at least about 4 weeks, and then the maintenance dose is administered approximately once a week for at least about 4 weeks, the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tildepazotide, 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 tildepazotide, 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 aspect, the present invention provides tildepazotide, or a pharmaceutically acceptable salt thereof, for use in treating chronic kidney disease. In another aspect, the present invention provides tildepazotide, or a pharmaceutically acceptable salt thereof, for use in treating chronic kidney disease in patients in need of treatment of chronic kidney disease, wherein the escalating dose is administered approximately once a week for at least about 4 weeks, and then the maintenance dose is administered approximately once a week for at least about 4 weeks, the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tildepazotide, 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 tildepazotide, 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 aspect, the present invention provides tildepazotide, or a pharmaceutically acceptable salt thereof, for use in treating atherosclerosis.In another aspect, the present invention provides tildepasib, or a pharmaceutically acceptable salt thereof, for use in treating atherosclerosis in a patient in need thereof, wherein the escalating dose is administered approximately once a week for at least about 4 weeks, followed by a maintenance dose administered approximately once a week for at least about 4 weeks, the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tildepasib, 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 tildepasib, 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 aspect, the present invention provides tildepasib, or a pharmaceutically acceptable salt thereof, for use in treating NAFLD. In another aspect, the present invention provides tildepasib, or a pharmaceutically acceptable salt thereof, for use in treating NAFLD in a patient in need thereof, wherein the escalating dose is administered approximately once a week for at least about 4 weeks, followed by a maintenance dose administered approximately once a week for at least about 4 weeks, the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tildepasib, 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 tildepasib, 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 aspect, the present invention provides tildepasib, or a pharmaceutically acceptable salt thereof, for use in treating NASH.In another aspect, the present invention provides tildesatide, or a pharmaceutically acceptable salt thereof, for use in treating NASH in patients in need thereof, wherein the escalating dose is administered approximately once a week for at least about 4 weeks, followed by a maintenance dose administered approximately once a week for at least about 4 weeks, the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tildesatide, 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 tildesatide, 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 aspect, the present invention provides tildesatide, or a pharmaceutically acceptable salt thereof, for use in curing diabetes, inducing remission or regression of diabetes, or preventing diabetes. In another aspect, the present invention provides tildesatide, or a pharmaceutically acceptable salt thereof, for use in curing diabetes, inducing remission or regression of diabetes, or preventing diabetes in patients in need thereof, wherein the escalating dose is administered approximately once a week for at least about 4 weeks, followed by a maintenance dose administered approximately once a week for at least about 4 weeks, the escalating dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tildesatide, 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 tildesatide, 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] One embodiment of the invention for such use has an escalating dose of about 2.5 mg administered once a week for 4 weeks and a maintenance dose of about 5.0 mg administered once a week for 4 weeks. A further embodiment of the invention has an escalating dose of about 7.5 mg administered once a week for 4 weeks and a maintenance dose of about 10.0 mg administered once a week for 4 weeks. A further embodiment of the invention has an escalating dose of about 12.5 mg administered once a week for 4 weeks and a maintenance dose of about 15.0 mg administered once a week for 4 weeks. A further embodiment of the invention has escalating doses of about 2.5 mg and about 7.5 mg administered once a week for 4 weeks and maintenance doses of about 5.0 mg and about 10.0 mg administered once a week for 4 weeks. A further embodiment of the invention has escalating doses of about 2.5 mg, about 5.0 mg and about 7.5 mg administered once a week for 4 weeks and maintenance doses of about 5.0 mg, about 10.0 mg and about 15.0 mg administered once a week for 4 weeks.

[0245] As used herein, "titer dose" or "escalating dose" means a dose less than the highest desired effective dose for a patient. As used herein, the invention contemplates that a "titer dose" or "escalating dose" may become a "maintenance dose" when the highest desired effective dose, or such a dose is observed to be the desired effective dose for a patient, and such a dose is administered chronically for a period exceeding 4 weeks.

[0246] As used herein, "maintenance dose" means both a dose that is the highest desired effective dose for a patient and, if such maintenance dose is less than the highest desired effective dose, a maintenance dose that can be a titration dose as the dose for a particular patient that will increase until it reaches the next highest maintenance dose contemplated by the present invention, for example, from at least about 7.5 mg for at least about two weeks to at least about 10 mg for at least about two weeks. The present invention contemplates that patients who reach a maintenance dose of about 10 mg or about 15 mg may need to have those doses decreased to a lower maintenance dose, as determined by a physician or other health care provider.

[0247] Also provided herein is tilsipatide for use in combination, simultaneously, individually, or sequentially, of one or more agents selected from the group consisting of metformin, thiazolidinedione, sulfonylurea, dipeptidyl peptidase 4 inhibitor, sodium glucose cotransporter, SGLT-2 inhibitor, growth differentiation factor 15 modulator (“GDF15”), peptide tyrosine tyrosine modulator (“PYY”), modified insulin, amylin, dual amylin calcitonin receptor agonist, and oxyntomodulin agonist (“OXM”) for treating a condition selected from the group consisting of type 2 diabetes, chronic kidney disease, atherosclerosis, NALFD, and NASH. Further provided herein is a compound of the invention for use in combination, simultaneously, individually, or sequentially, of one or more agents selected from metformin, thiazolidinedione, sulfonylurea, dipeptidyl peptidase 4 inhibitor, sodium glucose cotransporter, SGLT-2 inhibitor, GDF15, PYY, modified insulin, amylin, dual amylin calcitonin receptor agonist, and OXM in improving glycemic control and / or weight management. Also provided herein is a compound of the invention for use in combination, simultaneously, individually, or sequentially, of one or more agents selected from metformin, thiazolidinedione, sulfonylurea, dipeptidyl peptidase 4 inhibitor, sodium glucose cotransporter, SGLT-2 inhibitor, GDF15, PYY, modified insulin, amylin, dual amylin calcitonin receptor agonist, and OXM to cure diabetes, induce remission or regression of diabetes, or prevent diabetes. In one embodiment, the compounds herein are provided in a fixed-dose combination with one or more agents selected from metformin, thiazolidinedione, sulfonylurea, dipeptidyl peptidase 4 inhibitor, sodium glucose cotransporter, SGLT-2 inhibitor, GDF15, PYY, modified insulin, amylin, dual amylin calcitonin receptor agonist, 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 or no alcohol, and in one embodiment, the patient does not have co-existing diabetes. NAFLD is a major 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 accompanied by an etiological group showing macrovesicular steatosis, inflammation, hepatocyte ballooning, and fibrosis. NASH can lead to cirrhosis and liver failure. It is established that patients with NASH are at high risk of developing cirrhosis and have a high risk of cardiovascular death and hepatocellular carcinoma. This non-alcoholic, non-viral cirrhosis is actually one of the main causes of liver transplantation.

[0249] NAFLD and NASH are progressive diseases characterized by the development of hepatic fibrosis as NAFLD progresses to NASH. The stage of NASH can be defined, for example, by the NASH CRN (Clinical Research Network). The staging of fibrosis measures the amount and pattern of NASH fibrosis, and the parenchymal architectural remodeling of the patient. NASH is usually diagnosed in human patients using liver biopsy, and the diagnosis is predicted using proton density fat fraction images derived from MRI ("MRI-PDFF"), plasma cytokeratin 18 (CK18) fragment levels as biomarkers of hepatocyte apoptosis, plasma Pro-C3 (N-terminal type III procollagen propeptide) to predict the progression of fibrosis, 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, in which excessive lipid deposition occurs in the liver, is usually evaluated using diagnostic imaging methods such as MRI-PDFF.

[0250] Currently, there are no approved pharmaceuticals specific to the treatment of NASH. Current recommendations for NASH patients include dietary therapy and exercise. There is a need for pharmaceuticals to provide additional treatment options for patients suffering from NAFLD and NASH.

[0251] The present invention provides a method for treating NAFLD, which comprises administering to a patient in need thereof an effective amount of zilepatin or a pharmaceutically acceptable salt thereof. The present invention provides a method for treating NASH, which comprises administering to a patient in need thereof an effective amount of zilepatin or a pharmaceutically acceptable salt thereof. In one embodiment, the patient in need of treatment for NASH has co-existing 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 an abnormality of the structure or function of the kidneys that affects the health of a patient and persists for three months. CKD can be classified into five categories based on the 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 / 1.73 m2) is classified as stage 3 CKD. In the adult population, a decrease in GFR is associated with an increased risk of cardiovascular disease ("CVD") independent of other cardiovascular ("CV") risk factors. The CV mortality rate of patients with stage 3 and stage 4 CKD is two-fold and three-fold higher, respectively, 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. Thus, patients with CKD are considered to be at high risk (stage 3 CKD) or very high risk (stage 4 - 5 CKD or on dialysis). Treatment of patients with CKD typically includes dietary therapy, exercise, smoking cessation, antihypertensive medications, and combinations of medications. Desirable treatments for CKD reduce inflammation, improve glycemic 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 tilzerepatide 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 occurs when plaques accumulate in the arterial wall. This accumulation narrows the arteries and impedes blood flow. Atherosclerosis and the complications associated with atherosclerotic disease progression can cause heart attacks or strokes. Despite recent advances in treatment options, cardiovascular disease remains the leading cause of death in people with diabetes. The present invention provides a method for treating atherosclerosis, comprising administering an effective amount of tilzerepatide to a patient in need thereof.

[0255] Curing diabetes, inducing remission or regression of diabetes, or preventing diabetes US9,474,780 teaches that tilzerepatide is useful for the treatment of diabetes, and "treatment" includes suppressing, slowing, stopping, or reversing the progression or severity of existing symptoms or disorders. Despite advances in the treatment of diabetes, many patients undergoing such treatment are unable to achieve their blood glucose control or HbA1c targets.

[0256] US 9,474,780 teaches that tildesideptide is useful for the treatment of diabetes, and "treatment" includes suppressing, slowing, halting, or reversing the progression or severity of an existing condition or disorder. Despite advances in the treatment of diabetes, many patients undergoing such treatment are unable to achieve their blood glucose control goals or HbA1c goals. The present invention provides a cure for diabetes in which a patient undergoes treatment for diabetes using a tildesideptide dosing regimen that includes administering an initial or escalating dose of 2.5 mg of tildesideptide once a week for 4 weeks, followed by administering a maintenance dose of 5.0 mg of tildesideptide once a week for at least 4 weeks, but if the patient does not achieve their HbA1c goal, administering an escalating dose of approximately 7.5 mg once a week for at least 4 weeks, then administering a maintenance dose of 10.0 mg of tildesideptide once a week for at least 4 weeks, and where the patient is unable to achieve their HbA1c goal with at least 4 weeks of treatment using a 10.0 mg dose once a week, an escalating dose of 12.5 mg of tildesideptide can be administered once a week for at least 4 weeks, followed by administering a maintenance dose of 15 mg once a week until the HbA1C goal is achieved for at least about 2 weeks, and such patients maintain their HbA1c goal even after discontinuing all drugs approved for use in the treatment of diabetes or blood glucose control. As used herein, terms such as "diabetes drug," "diabetes medicine," etc. mean drugs approved by the relevant regulatory authorities for use in the treatment of blood glucose control or type II diabetes. In one embodiment, the HbA1c measurement of a patient undergoing treatment for diabetes is about 5.9% or less. In one embodiment, the patient maintains their HbA1c target level for at least 1 month without further administration of tildesideptide. In one embodiment, a patient who has previously undergone treatment for diabetes using tildesideptide maintains their blood glucose goal for at least 1 month without administering further tildesideptide or other diabetes drugs. In one embodiment, the patient maintains their blood glucose goal for at least 6 months without administering further tildesideptide or other diabetes drugs.

[0257] As used herein, terms such as "diabetes drug" and "diabetes medicine" mean drugs approved by the relevant regulatory authorities for use in blood glucose control or the treatment of type II diabetes. In one embodiment, the HbA1c measurement of a patient undergoing diabetes treatment 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 received diabetes treatment with tirzepatide maintains the blood glucose target for at least one month without administration of further tirzepatide or other diabetes drugs. In one embodiment, the patient maintains the blood glucose target for at least six months without administration of further tirzepatide or other diabetes drugs.

[0258] The dosages 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 prefilled syringes. Such prefilled syringes may be useful for administering 0.5 milliliters of such composition per dose per patient. The dosages of the present invention are typically administered subcutaneously. The dosages are typically administered using a prefilled disposable pen, a reusable pen, or an autoinjector pen. In one embodiment, the device is an autoinjector device described by U.S. Patent No. 8,734,394.

[0259] As used herein, "tirzepatide" means a GIP / GLP1 dual agonist peptide described in US9,474,780 and described by CAS Registry Number: 2023788-19-2.

[0260] Tirzepatide 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 chemically modified through the bond to the epsilon - amino group of the K side chain of (2 - [2 - (2 - amino - ethoxy) - ethoxy] - acetyl)2 - (γGlu)1 - CO - (CH2) 18 -CO2H, and the C - terminal amino acid is amidated as a C - terminal primary amide (SEQ ID NO: 1).

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

[0262] As used herein, the terms "increase in dose", "increase in maintenance dose", "increase in titration dose", and "increase in escalating dose" mean an increase in each respective dose by a nurse, healthcare provider, patient, or any other individual.

[0263] As used herein, "pharmaceutically acceptable salts" are well - known to those skilled in the art. In one embodiment, it is a pharmaceutically acceptable salt which is the tiludronate trifluoroacetate salt. In one embodiment, it is tiludronate as the non - salt form.

[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 usually correlate (either directly or inversely) quantitatively with the progression of the disease. In the context of a clinical trial, a biomarker is a measure of the effect of a particular treatment and may correlate with an actual clinical endpoint, but not necessarily with an exact relationship, i.e., a biomarker is an alternative means to a clinical endpoint.

[0265] As used herein, the terms "treatment", "treating", "treatment of", etc. mean including delaying or reducing the progression of a disease or disorder. This term includes alleviating, improving, or reducing one or more symptoms of a disorder or condition, even if the disorder or condition is not eliminated or the progression is not slowed down.

[0266] As used herein, "cure of diabetes" means that a patient using tirzepatide for the treatment of diabetes reaches the glycemic control treatment goal. Tirzepatide treatment for curing diabetes can prevent, reduce the severity of, or induce remission of diabetes in such patients. In one embodiment, tirzepatide treatment delays the progression of diabetes in patients who require such treatment. In one embodiment, a patient using tirzepatide for the treatment of diabetes achieves the glycemic control treatment goal and does not require concomitant diabetes medications to maintain the glycemic control goal. In one embodiment, a patient using tirzepatide for the treatment of diabetes reaches at least the glycemic control treatment goal, and the treatment goal is maintained with the discontinuation of treatment using tirzepatide and all other diabetes medications. In one embodiment, a patient using tirzepatide for the treatment of diabetes reaches at least the glycemic control treatment goal, and the treatment goal is maintained for at least about 1 month with the discontinuation of treatment using tirzepatide and all other diabetes medications. In one embodiment, a patient using tirzepatide for the treatment of diabetes reaches at least the glycemic control treatment goal, and the treatment goal is maintained for at least about 6 months with the discontinuation of treatment using tirzepatide and all other diabetes medications. In one embodiment, a patient is unable to achieve the glycemic goal prior to tirzepatide treatment. In one embodiment, a patient was unable to achieve the glycemic goal using oral diabetes medications. In one embodiment, a patient was unable to achieve the glycemic goal using metformin treatment. In one embodiment, the patient's glycemic goal is less than about 5.9% HbA1c.

[0267] As used herein, "glycemic control" refers to the maintenance or reduction of a patient's HbA1c level, and "improvement" in glycemic control refers to a reduction in HbA1c.

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

[0269] As used herein, "HbA1c" refers to the level of glycated hemoglobin that occurs when hemoglobin binds to glucose in the blood. The HbA1c level is a commonly used measure of glycemic control in patients with diabetes, and a reduction in the HbA1c level generally indicates an improvement in glycemic control. In connection with the methods of the present invention, the methods of the present invention result in a reduction in HbA1c. In certain embodiments, the reduction in HbA1c is reduced compared to the HbA1c level resulting from treatment with a lower dose of tildepep.

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

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

[0272] Preparation #1 - Tildepep composition containing NaCl The composition is prepared substantially as described herein. Compositions containing 5, 10, 15, 20, 15, and 30 mg / mL of tildepazide each contain the components listed in Table 1. An acid or base is optionally added to achieve the desired pH range. Water is added in a quantity sufficient (q.s.) to a total final volume of 1 milliliter.

Table 1

[0273] Tildepazide Composition Containing #2 - Propylene Glycol The composition is prepared substantially as described herein. Compositions providing compositions of 5, 10, 15, 20, 15, and 30 mg / mL of tildepazide each contain the components listed in Table 2. An acid or base is optionally added to achieve the desired pH range. Water is added in a quantity sufficient to a total final volume of 1 milliliter.

Table 2

[0274] Clinical Trial (NCT03131687) Supporting Maintenance Dose Embodiments A 6 - month (26 - week) Phase 2 double - blind clinical trial was designed to evaluate the safety, efficacy, PK / PD of four dose levels (1 mg, 5 mg, 10 mg, 15 mg respectively) of tildepazide administered once weekly by subcutaneous injection, regardless of the presence of a stable dose of metformin, in patients with T2DM with inadequate glycemic control by diet and exercise, compared to dulaglutide 1.5 mg once weekly (QW) and placebo QW. The dose of tildepazide is up - titrated to the maintenance dose using the following weekly dose increments.

Table 3

[0275] This study also has a 4-week follow-up period. In addition to safety and efficacy for treating T2DM, efficacy endpoints include the effects of tirzepatide on HbA1c, FBG, body weight, lipids, and waist circumference compared to placebo and dulaglutide 1.5 mg. In this study, the effects of tirzepatide on GI tolerance, hypoglycemia, hypersensitivity reactions, pancreatic safety, and the development of antidrug antibodies due to treatment are also evaluated. A model-based dose-response analysis is performed to predict the potential for significant HbA1c reduction and weight loss in longer studies.

[0276] Statistical Analysis Efficacy: The primary efficacy result of the change in HbA1c from baseline to the 26-week endpoint is analyzed using a Bayesian dose-response model. The analysis is performed with the intention of processing the population (mITT) analysis set. The analysis supporting the primary efficacy result of the mITT dataset is a model of the obesity index (BMI) (<30 kg / m 2 , ≥30 kg / m 2 ) as a fixed effect, metformin use, treatment, visit, the interaction between treatment and visit, baseline HbA1c as a covariate, and post-baseline measurements (MMRM) of patients as a variable effect.

[0277] The mean change in body weight from baseline at 12 and 26 weeks, and the mean change in HbA1c from baseline at 12 weeks are analyzed using a dose-response model similar to the primary analysis. The proportion of patients with a weight loss of ≥5% or ≥10%, the proportion of patients who have reached the target of ≤6.5% or ≤7.0% HbA1c at 26 weeks, or the proportion of patients who require rescue therapy are analyzed using logistic regression regarding the fixed effect of treatment and strata and baseline as covariates. The FBG (fasting blood glucose), SMBG (self-monitoring blood glucose) levels from baseline to 12 and 26 weeks, the change in waist circumference from baseline, and the mean change rate of lipids are analyzed using an MMRM similar to that used in the primary analysis.

[0278] Abbreviations in the table: Dula 1.5mg = dulaglutide 1.5mg once a week, LY means tirzepatide, LY 1mg = tirzepatide 1mg once a week, LY 5mg = 5mg once a week, LY 10mg = tirzepatide once a week, maximum dose is the escalating dose group of 10mg, LY 15mg = tirzepatide once a week, escalating dose group with a maximum dose of 15mg, 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 = modified intent-to-treat, SD = standard deviation. In the case of Table 4, n = number of patients in the population with baseline values and post-baseline values at the specified time points. In the case of Table 6, LY10mg = tirzepatide once a week, maximum dose is the escalating dose group of 10mg, escalating dose: (5mg at week 0 and week 1), LY15mg = tirzepatide once a week, maximum dose is the escalating dose group of 15mg, escalating dose: (5mg at week 0 and week 1, 10mg from week 2 to week 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), % = proportion of patients who spent at least some time in the treatment group and experienced a new event during the interval. In the case of Table 7, n is the number of patients with an event meeting the criteria, N is the number of patients in the population, and % is the proportion of patients in the treatment group experiencing the event.

Table 4

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

[0280] The percentage of patients who achieved the HbA1c treatment goal in Table 3 indicates that more patients in the tirzepatide 15 mg group who continued the investigational drug were able to achieve the HbA1c treatment goal of ≤5.7% than in any other treatment group.

Table 5

[0281] As shown in Table 4, as expected from the observed changes in HbA1c, the doses of tirzepatide 5 mg, 10 mg, and 15 mg significantly decreased 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 goals of ≥5%, ≥10%, and ≥15% at 26 weeks. The doses of tirzepatide 5 mg, 10 mg, and 15 mg significantly decreased body weight from baseline and were significantly different from placebo. The groups of tirzepatide 5 mg, 10 mg, and 15 mg were also significantly different from dulaglutide 1.5 mg.

[0283] As shown in Table 5 summarizing the clinical trials, the majority of patients in the tirzepatide 15 mg group were able to achieve an average weight loss of more than 15%.

Table 7

[0284] Table 6 shows the beneficial effect on the incidence of gastrointestinal adverse events using the methods of this specification.

Table 8

[0285] Reduced appetite is a centrally mediated effect. The data shown in Table 7 are from clinical trials and suggest that tirzepatide has a centrally mediated effect. The centrally mediated activity of tirzepatide may provide additional treatment options for patients seeking treatment that provides centrally mediated GIP / GLP1 agonist activity.

[0286] In NCT03131687, the 15 mg dose was associated with high GI AEs and a high frequency of patients discontinuing the trial treatment early after a relatively short ramp-up. A 15 mg dose with a more acceptable tolerability profile is desirable. The data from NCT03131687 support a 15 mg dose as the highest clinically relevant maintenance dose as contemplated by the present invention. The ramp-up scheme as claimed herein was investigated to facilitate an acceptable tolerable 15 mg maintenance dose. See the clinical trial (NCT03311724) immediately below.

[0287] Clinical trial (NCT03311724) supporting 2.5 ramp increments This is a 12-week treatment that includes a 1-week screening (Visit 1), followed by a 1-week introduction (Visit 2), then 12 weeks of treatment (Visits 3-10, including phone visits), followed by a 4-week safety follow-up. This is a Phase 2 trial designed to examine the efficacy and tolerability of once-weekly subcutaneous tirzepatide compared to placebo in patients with type 2 diabetes with inadequate glycemic control on diet and exercise alone or on a stable dose of metformin. This trial was designed as follows and conducted to refine the ramp-up scheme.

Table 9

Table 10

[0288] As shown in Table 8, after 12 weeks of treatment, including an 8-week incremental period, the placebo-adjusted changes in HbA1c at 12 mg and 15 mg of tirzepatide doses were statistically significant and clinically meaningful.

Table 11

[0289] As shown in Table 9, at 12 weeks, both doses of tirzepatide were significantly reduced 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 events were mild to moderate. There were no patients who discontinued the clinical trial due to gastrointestinal tolerance adverse events or other adverse events.

[0291] Based on these above data from NCT03311724, an incremental scheme using a 2.5 mg dose increment per 4 weeks is further supported.

[0292] Biomarkers In clinical trials, clinically relevant biomarkers are measured 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. Clinical 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 for predicting NAFLD are observed during clinical trials to demonstrate the beneficial effects of tildesepatide in the treatment of NAFLD. Biomarkers for predicting NASH are observed during clinical trials to demonstrate the beneficial effects of tildesepatide in the treatment of NAFLD. The HbA1c levels of patients who received tildesepatide treatment and achieved the target of blood glucose control and discontinued the use of diabetes medications are measured during follow-up to verify the cure of diabetes in such patients.

[0294] Example 1 Clinical dosing schedule Clinical trials examining the three maintenance doses (5.0 mg, 10.0 mg, and 15.0 mg) of the present invention in the dosing schedule of the present invention are conducted as follows.

[0295] The starting dose of tildesepatide is 2.5 mg once a week for 4 weeks, and then increases to 5 mg once a week during the trial period of the low-dose group.

[0296] In the case of the 10 mg group, the starting dose of tildesepatide is 2.5 mg once a week for 4 weeks, and then the dose is increased by 2.5 mg every 4 weeks until it reaches the dose of 10 mg and maintains it during the trial period (5 mg once a week for 4 weeks, then 7.5 mg once a week for 4 weeks).

[0297] In the case of the 15 mg group, the starting dose of tildesepatide is 2.5 mg once a week for 4 weeks, and then the dose is increased by 2.5 mg every 4 weeks until it reaches the dose of 15 mg of tildesepatide and maintains it during the trial period (5 mg once a week for 4 weeks, then 7.5 mg once a week for 4 weeks, then 10 mg once a week for 4 weeks, then 12.5 mg once a week for 4 weeks). For patients who cannot tolerate the 15 mg dose, the maintenance dose can be reduced to 10 mg.

[0298] Sequence SEQ ID NO:1 Tildesepatide YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS In the sequence, X1 is Aib, X2 is Aib, and the K at position 20 is chemically modified through the bond to the epsilon-amino group of the K side chain of (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)1-CO-(CH2) 18 -CO2H, and the C-terminal amino acid is amidated as a C-terminal primary amide.

Claims

1. A pharmaceutical composition comprising tildepagliflozin or a pharmaceutically acceptable salt thereof for use in treating type 2 diabetes in patients in need of treatment for type 2 diabetes, wherein an escalating dose for at least one administration is administered once a week for at least 4 weeks, and after said escalating dose, a maintenance dose for at least one administration is administered once a week for at least 4 weeks, characterized in that the escalating dose is selected from the group consisting of 2.5 mg, 7.5 mg and 12.5 mg of tildepagliflozin or a pharmaceutically acceptable salt thereof, the first escalating dose administered is 2.5 mg, the maintenance dose after the escalating dose is an increment of 2.5 mg, and the maintenance dose is selected from the group consisting of 5.0 mg, 10.0 mg and 15.0 mg of tildepagliflozin or a pharmaceutically acceptable salt thereof.

2. The composition according to claim 1, wherein the escalating dose is 2.5 mg and the maintenance dose is 5.0 mg.

3. The composition according to claim 1, wherein the escalating dose is 7.5 mg and the maintenance dose is 10.0 mg.

4. The composition according to claim 1, wherein the escalating dose is 12.5 mg and the maintenance dose is 15.0 mg.

5. A pharmaceutical composition comprising tildepagliflozin or a pharmaceutically acceptable salt thereof for use in inducing remission or regression of diabetes in patients in need of inducing remission or regression of diabetes, wherein an escalating dose for at least one administration is administered once a week for at least 4 weeks, and after said escalating dose, a maintenance dose for at least one administration is administered once a week for at least 4 weeks, characterized in that the escalating dose is selected from the group consisting of 2.5 mg, 7.5 mg and 12.5 mg of tildepagliflozin or a pharmaceutically acceptable salt thereof, the first escalating dose administered is 2.5 mg, the maintenance dose after the escalating dose is an increment of 2.5 mg, and the maintenance dose is selected from the group consisting of 5.0 mg, 10.0 mg and 15.0 mg of tildepagliflozin or a pharmaceutically acceptable salt thereof.

6. The composition according to claim 5, wherein the escalating dose is 2.5 mg and the maintenance dose is 5.0 mg.

7. The composition according to claim 5, wherein the escalating dose is 7.5 mg and the maintenance dose is 10.0 mg.

8. The composition according to claim 5, wherein the escalating dose is 12.5 mg and the maintenance dose is 15.0 mg.

9. A pharmaceutical composition comprising tildepazide or a pharmaceutically acceptable salt thereof for use in preventing diabetes in patients in need of diabetes prevention, wherein at least one escalating dose is administered once a week for at least 4 weeks, and after said escalating dose, at least one maintenance dose is administered once a week for at least 4 weeks, characterized in that the escalating dose is selected from the group consisting of 2.5 mg, 7.5 mg and 12.5 mg of tildepazide or a pharmaceutically acceptable salt thereof, the first escalating dose administered is 2.5 mg, the maintenance dose after the escalating dose is an increment of 2.5 mg, and the maintenance dose is selected from the group consisting of 5.0 mg, 10.0 mg and 15.0 mg of tildepazide or a pharmaceutically acceptable salt thereof.

10. The composition according to claim 9, wherein the escalating dose is 2.5 mg and the maintenance dose is 5.0 mg.

11. The composition according to claim 9, wherein the escalating dose is 7.5 mg and the maintenance dose is 10.0 mg.

12. The composition according to claim 9, wherein the escalating dose is 12.5 mg and the maintenance dose is 15.0 mg.

13. A pharmaceutical composition comprising tirzepatide or a pharmaceutically acceptable salt thereof for use in improving weight management in patients in need of improving weight management, wherein at least one incremental dose is administered once a week for at least 4 weeks, and after said incremental dose, at least one maintenance dose is administered once a week for at least 4 weeks, characterized in that said incremental dose is selected from the group consisting of 2.5 mg, 7.5 mg and 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof, the first incremental dose administered is 2.5 mg, the maintenance dose after the incremental dose is an increment of 2.5 mg, and said maintenance dose is selected from the group consisting of 5.0 mg, 10.0 mg and 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof.

14. The composition according to claim 13, wherein said incremental dose is 2.5 mg and said maintenance dose is 5.0 mg.

15. The composition according to claim 13, wherein said incremental dose is 7.5 mg and said maintenance dose is 10.0 mg.

16. The composition according to claim 13, wherein said incremental dose is 12.5 mg and said maintenance dose is 15.0 mg.

17. A pharmaceutical composition comprising tirzepatide or a pharmaceutically acceptable salt thereof for use in treating non-alcoholic fatty liver disease in patients in need of treating non-alcoholic fatty liver disease, wherein at least one incremental dose is administered once a week for at least 4 weeks, and after said incremental dose, at least one maintenance dose is administered once a week for at least 4 weeks, characterized in that said incremental dose is selected from the group consisting of 2.5 mg, 7.5 mg and 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof, the first incremental dose administered is 2.5 mg, the maintenance dose after the incremental dose is an increment of 2.5 mg, and said maintenance dose is selected from the group consisting of 5.0 mg, 10.0 mg and 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof.

18. The composition according to claim 17, wherein the escalating dose is 2.5 mg and the maintenance dose is 5.0 mg.

19. The composition according to claim 17, wherein the escalating dose is 7.5 mg and the maintenance dose is 10.0 mg.

20. The composition according to claim 17, wherein the escalating dose is 12.5 mg and the maintenance dose is 15.0 mg.

21. A pharmaceutical composition comprising tildesepatide or a pharmaceutically acceptable salt thereof for use in treating non-alcoholic steatohepatitis in patients in need thereof, wherein the escalating dose for at least one administration is administered once a week for at least 4 weeks, and after the escalating dose, the maintenance dose for at least one administration is administered once a week for at least 4 weeks, characterized in that the escalating dose is selected from the group consisting of 2.5 mg, 7.5 mg and 12.5 mg of tildesepatide or a pharmaceutically acceptable salt thereof, the first escalating dose administered is 2.5 mg, the maintenance dose after the escalating dose is an increment of 2.5 mg, and the maintenance dose is selected from the group consisting of 5.0 mg, 10.0 mg and 15.0 mg of tildesepatide or a pharmaceutically acceptable salt thereof.

22. The composition according to claim 21, wherein the escalating dose is 2.5 mg and the maintenance dose is 5.0 mg.

23. The composition according to claim 21, wherein the escalating dose is 7.5 mg and the maintenance dose is 10.0 mg.

24. The composition according to claim 21, wherein the escalating dose is 12.5 mg and the maintenance dose is 15.0 mg.

25. A pharmaceutical composition comprising tildesepatide or a pharmaceutically acceptable salt thereof for use in treating diabetic kidney disease in a patient in need of treatment for diabetic kidney disease, wherein at least one incremental dose is administered once a week for at least 4 weeks, and after said incremental dose, at least one maintenance dose is administered once a week for at least 4 weeks, characterized in that the incremental dose is selected from the group consisting of 2.5 mg, 7.5 mg and 12.5 mg of tildesepatide or a pharmaceutically acceptable salt thereof, the first incremental dose administered is 2.5 mg, the maintenance dose after the incremental dose is an increment of 2.5 mg, and the maintenance dose is selected from the group consisting of 5.0 mg, 10.0 mg and 15.0 mg of tildesepatide or a pharmaceutically acceptable salt thereof. **Claim 26** The composition according to claim 25, wherein the incremental dose is 2.5 mg and the maintenance dose is 5.0 mg. **Claim 27** The composition according to claim 25, wherein the incremental dose is 7.5 mg and the maintenance dose is 10.0 mg. **Claim 28** The composition according to claim 25, wherein the incremental dose is 12.5 mg and the maintenance dose is 15.0 mg.

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