Methods of using GIP / GLP1 co-agonists for treatment

Abstract

The present invention provides a method of increasing glycemic control in a patient in need thereof by administering tizatide, or a pharmaceutically acceptable salt thereof. The present invention provides a method of improving body weight management in a patient in need thereof by administering tizatide, or a pharmaceutically acceptable salt thereof. Also provided is a method of treating a condition selected from the group consisting of atherosclerosis, chronic kidney disease, NAFLD and NASH. Also provided is a method of preventing or causing alleviation of diabetes mellitus, comprising administering tizatide or a pharmaceutically acceptable salt thereof. Also provided is a dosing regimen for increasing glycemic control, improving weight management, and / or treating dyslipidemia.

Description

[0001] This application is a divisional application of Chinese Patent Application No. 201980049182.2, filed on July 22, 2019, entitled “Methods of Treatment Using GIP / GLP1 Co-Agonist Peptides.”

[0002] The present invention provides methods of treating type 2 diabetes (T2D) using new dosages of the glucose-dependent insulinotropic polypeptide (GIP) / glucagon-like peptide-1 (GLP1) dual agonist peptide tirzepatide, or a pharmaceutically acceptable salt thereof. In addition, the present invention provides methods of treating type 2 diabetes using new dosing regimens of the GIP / GLP1 dual agonist peptide tirzepatide, or a pharmaceutically acceptable salt thereof. In addition, the present invention provides new medical uses of tirzepatide, or a pharmaceutically acceptable salt thereof. More specifically, the present invention provides methods of treating a disorder selected from chronic kidney disease, atherosclerosis, nonalcoholic fatty liver disease (“NAFLD”), and nonalcoholic steatohepatitis (“NASH”). In another embodiment, the present invention provides methods of curing diabetes in certain patients.

[0003] Diabetes mellitus is a chronic disorder characterized by hyperglycemia due to 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.

[0004] US9474780 generally describes compositions containing GIP / GLP1 co-agonists administered by parenteral routes, and generally discloses a broad range of dosages up to about 30 mg per person per week. US9474780 discloses the use of GIP / GLP1 co-agonists to treat diabetes, obesity, and other conditions. US9474780 describes and claims tirzepatide.

[0005] It is well known that GLP1 therapy is associated with nausea, vomiting, and / or diarrhea. For example, one study reported that all GLP-1 receptor dosing regimens significantly increased the incidence of gastrointestinal adverse events. Diabetes Technol Ther. 2015 Jan; 17(1): 35-42. Additionally, previous clinical trials of GIP / GLP1 co-agonist compounds have been conducted and found that tolerability at high doses was 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 associated with gastrointestinal adverse events can hinder dosing to achieve the desired effective dose, can undermine patient treatment compliance, and can limit the effectiveness of the treatment regimen.

[0006] New tirzepatide dosages are needed to provide the desired glycemic control, e.g., as demonstrated by further reductions in HbA1c and / or weight loss, while maintaining an acceptable safety and adverse event profile. New tirzepatide dosing regimens are also needed to provide the desired glycemic control, e.g., as demonstrated by further reductions in HbA1c and / or weight loss, while maintaining an acceptable safety and adverse event profile. Additionally, there is a need for GIP / GLP1 dual agonist treatment options for conditions selected from chronic kidney disease, atherosclerosis, NAFLD, and NASH. Additionally, there is a need for treatments that cure diabetes by preventing diabetes, reducing its severity, or causing its remission. There is a need for treatments that reduce or delay the progression of diabetes.

[0007] The present invention provides a new tirzepatide dosing regimen for use in the aforementioned therapies, comprising a maintenance dose selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg. In another embodiment, the present invention provides a new dosing regimen comprising an escalation dose (i.e., a dose lower than the required maintenance dose) and a maintenance dose. In another embodiment, the present invention provides a new dosing regimen comprising one or more escalation doses and one or more maintenance doses. The present invention provides a new dosing regimen comprising administering at least one escalation dose approximately once a week for a minimum of about four weeks, and subsequently administering at least one maintenance dose approximately once a week for a minimum of about four weeks. In certain embodiments, the dose may be administered for about four weeks. In certain embodiments, the dose may be administered for more than about four weeks, as determined by the nurse, patient, and / or healthcare provider. For example, the maintenance dose may be administered for more than about four weeks. In certain embodiments of the present invention, if additional glycemic control is required with or without an intervening escalation dose, the maintenance dose of the present invention may be increased to the next highest maintenance dose of the present invention. For example, in one dosing regimen of the present invention, the escalation dose is about 2.5 mg and the maintenance dose is about 5.0 mg. In another dosage regimen of the present invention, the two ascending doses are about 2.5 mg and about 7.5 mg and the maintenance dose is about 5.0 mg and 10.0 mg. In another aspect of the present invention, the ascending dose is about 2.5 mg, about 7.5 mg and about 12.5 mg and the maintenance dose is about 5.0 mg, about 10.0 mg and about 15.0 mg. The ascending dose includes about 2.5 mg, about 7.5 mg and about 12.5 mg. The maintenance dose includes about 5.0 mg, about 10.0 mg and about 15.0 mg. The ascending dose of 2.5 mg can be the initial dose or starting dose of the dosage regimen provided herein. As used herein, the term "increment" or "incremental dose" refers to titration or titration dose as described herein.

[0008] Thus, the present invention provides a method for treating type 2 diabetes in a patient in need thereof, the method comprising administering an ascending dose about once a week for a minimum of about four weeks, followed by administering a maintenance dose about once a week for a minimum of about four weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is an incremental increase of 2.5 mg relative to the ascending dose. An embodiment of the present invention is therefore a method for treating type 2 diabetes, wherein the ascending dose administered about once a week for at least about four weeks is about 2.5 mg and the maintenance dose administered about once a week for at least about four weeks is about 5.0 mg. Another embodiment of the present invention is a method, wherein the ascending dose administered about once a week for at least about four weeks is about 7.5 mg and the maintenance dose administered about once a week for at least about four weeks is about 10.0 mg. Another embodiment of the present invention is a method in which the incremental dose for at least about four weeks of approximately weekly administration is about 12.5 mg and the maintenance dose for at least about four weeks of approximately weekly administration is about 15.0 mg. Another embodiment of the present invention is wherein after the first maintenance dose has been administered for at least about four weeks, the second incremental dose is administered for at least about four weeks approximately once a week and subsequently the second maintenance dose is administered for at least about four weeks approximately once a week. Such a method therefore includes an incremental dose of about 2.5 mg and about 7.5 mg and a maintenance dose of about 5.0 mg and about 10.0 mg. Another embodiment of the present invention is wherein after the second maintenance dose has been administered for at least about four weeks, the third incremental dose is administered for at least about four weeks approximately once a week and subsequently the third maintenance dose is administered for at least about four weeks approximately once a week. Such a method therefore includes an incremental dose of about 2.5 mg, about 7.5 mg, and about 12.5 mg and a maintenance dose of about 5.0 mg, about 10.0 mg, and about 15.0 mg.

[0009] As indicated above, in certain embodiments of the present invention, if additional glycemic control is required, with or without intervening ascending doses, the maintenance dose can be increased to a subsequent maintenance dose. Thus, the present invention also provides a method of treating type 2 diabetes in a patient in need thereof, comprising: administering ascending doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once a week for a minimum of about four weeks, followed by a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once a week for a minimum of about four weeks; and optionally thereafter, administering a second maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once a week for a minimum of about four weeks; and optionally thereafter, administering a third maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once a week for a minimum of about four weeks.

[0010] In another aspect, the present invention provides a method of treating type 2 diabetes in a patient in need thereof, the method comprising:

[0011] a) administering to said patient a dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once a week for a minimum of about four weeks;

[0012] b) increasing the dose to a dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, and administering it to the patient about once a week for a minimum of about four weeks;

[0013] c) increasing the dose to a dose of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, and administering it to the patient about once a week for a minimum of about four weeks;

[0014] d) increasing the dose to a dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, and administering it to the patient about once a week for a minimum of about four weeks;

[0015] e) increasing the dose to a dose of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, and administering it to the patient about once a week for a minimum of about four weeks; and

[0016] f) increasing the dose to a dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, and administering it to the patient about once a week for a minimum of about four weeks;

[0017] In one aspect, the present invention provides a method of treating type 2 diabetes in a patient in need thereof, the method comprising:

[0018] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0019] b) administering to the patient about once a week for at least about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0020] In another aspect, the present application provides a method of treating type 2 diabetes in a patient in need thereof comprising: administering to the patient about once a week for at least about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0021] Another embodiment provides a method of treating type 2 diabetes in a patient in need thereof comprising:

[0022] a) administering to the patient about once a week for at least about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0023] b) administering to the patient about once a week for at least about four weeks a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0024] Another embodiment provides a method of treating type 2 diabetes in a patient in need thereof comprising:

[0025] a) administering to the patient about once a week for at least about four weeks an escalation dose of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0026] b) administering to the patient about once a week for at least about four weeks a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0027] In another aspect, the present application provides a method of treating type 2 diabetes in a patient in need thereof comprising: administering to the patient about once a week for at least about four weeks a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0028] Another embodiment provides a method of treating type 2 diabetes in a patient in need thereof comprising:

[0029] a) administering to the patient about once a week for at least about four weeks a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0030] b) administering to the patient about once a week for at least about four weeks a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0031] Another embodiment provides a method of treating type 2 diabetes in a patient in need thereof comprising:

[0032] a) administering to said patient increasing doses of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0033] b) administering to said patient a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0034] In another aspect, the present invention provides a method of treating type 2 diabetes in a patient in need thereof, comprising administering to the patient a maintenance dose of about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

[0035] In another aspect, the present invention provides a method of treating type 2 diabetes in a patient in need thereof, the method comprising:

[0036] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0037] b) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0038] c) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0039] d) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0040] In another aspect, the invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg ascending doses.

[0041] In another aspect, the present invention provides a method of treating type 2 diabetes in a patient in need thereof, the method comprising:

[0042] g) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0043] h) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0044] i) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0045] j) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0046] k) administering to said patient increasing doses of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0047] 1) administering to said patient a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0048] In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg ascending doses. In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 12.5 mg ascending doses. In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg and 12.5 mg ascending doses.

[0049] In addition, the present invention provides a method of improving glycemic control in a patient in need thereof, the method comprising: administering at least one ascending dose about once a week for a minimum of about four weeks and administering at least one maintenance dose about once a week for a minimum of about four weeks after the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose after the ascending dose is an incremental increase of 2.5 mg relative to the ascending dose. An embodiment of the present invention is therefore a method of improving glycemic control, wherein the ascending dose administered about once a week for at least about four weeks is about 2.5 mg and the maintenance dose administered about once a week for at least about four weeks is about 5.0 mg. Another embodiment of the present invention is a method, wherein the ascending dose administered about once a week for at least about four weeks is about 7.5 mg and the maintenance dose administered about once a week for at least about four weeks is about 10.0 mg. Another embodiment of the present invention is a method in which the incremental dose for at least about four weeks of approximately weekly administration is about 12.5 mg and the maintenance dose for at least about four weeks of approximately weekly administration is about 15.0 mg. Another embodiment of the present invention is wherein after the first maintenance dose has been administered for at least about four weeks, the second incremental dose is administered for at least about four weeks approximately once a week and subsequently the second maintenance dose is administered for at least about four weeks approximately once a week. Such a method therefore includes an incremental dose of about 2.5 mg and about 7.5 mg and a maintenance dose of about 5.0 mg and about 10.0 mg. Another embodiment of the present invention is wherein after the second maintenance dose has been administered for at least about four weeks, the third incremental dose is administered for at least about four weeks approximately once a week and subsequently the third maintenance dose is administered for at least about four weeks approximately once a week. Such a method therefore includes an incremental dose of about 2.5 mg, about 7.5 mg, and about 12.5 mg and a maintenance dose of about 5.0 mg, about 10.0 mg, and about 15.0 mg.

[0050] As indicated above, in certain embodiments, if additional glycemic control is needed with or without an intervening escalation dose, the maintenance dose can be increased to a subsequent maintenance dose. Accordingly, the present application also provides a method of improving glycemic control in a patient in need thereof comprising: administering to the patient about once weekly for a minimum of about four weeks an escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, and thereafter administering to the patient about once weekly for a minimum of about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and, optionally thereafter, administering to the patient about once weekly for a minimum of about four weeks a second maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and, optionally thereafter, administering to the patient about once weekly for a minimum of about four weeks a third maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0051] Further, the present application provides a method of improving glycemic control in a patient in need thereof comprising:

[0052] a) administering to the patient about once weekly for a minimum of about four weeks an escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0053] b) administering to the patient about once weekly for a minimum of about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0054] In another aspect the present application provides a method of improving glycemic control in a patient in need thereof comprising: administering to the patient about once weekly for a minimum of about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0055] Another embodiment provides a method of improving glycemic control in a patient in need thereof comprising:

[0056] a) administering to the patient about once weekly for a minimum of about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0057] b) administering to the patient about once weekly for a minimum of about four weeks a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0058] Another embodiment provides a method of improving glycemic control in a patient in need thereof comprising:

[0059] a) administering to the patient about once weekly for a minimum of about four weeks an escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0060] b) administering to the patient about 10.0 mg once about weekly of tirzepatide, or a pharmaceutically acceptable salt thereof, for a minimum of about four weeks.

[0061] In another aspect the present application provides a method for improving glycemic control in a patient in need thereof comprising: administering to the patient about 10.0 mg once about weekly of tirzepatide, or a pharmaceutically acceptable salt thereof, for a minimum of about four weeks.

[0062] Another embodiment provides a method for improving glycemic control in a patient in need thereof comprising:

[0063] a) administering to the patient about 10.0 mg once about weekly of tirzepatide, or a pharmaceutically acceptable salt thereof, for a minimum of about four weeks; and subsequently

[0064] b) administering to the patient about 15.0 mg once about weekly of tirzepatide, or a pharmaceutically acceptable salt thereof, for a minimum of about four weeks.

[0065] Another embodiment provides a method for improving glycemic control in a patient in need thereof comprising:

[0066] a) administering to the patient about 12.5 mg once about weekly of tirzepatide, or a pharmaceutically acceptable salt thereof, for a minimum of about four weeks; and subsequently

[0067] b) administering to the patient about 15.0 mg once about weekly of tirzepatide, or a pharmaceutically acceptable salt thereof, for a minimum of about four weeks.

[0068] In another aspect the present application provides a method for improving glycemic control in a patient in need thereof comprising: administering to the patient about 15.0 mg once about weekly of tirzepatide, or a pharmaceutically acceptable salt thereof, for a minimum of about four weeks.

[0069] In another aspect the present application provides a method for improving glycemic control in a patient in need thereof comprising:

[0070] a) administering to the patient about 2.5 mg once about weekly of tirzepatide, or a pharmaceutically acceptable salt thereof, for a minimum of about four weeks; and subsequently

[0071] b) administering to the patient about 5.0 mg once about weekly of tirzepatide, or a pharmaceutically acceptable salt thereof, for a minimum of about four weeks; and subsequently

[0072] c) administering to the patient about 7.5 mg once about weekly of tirzepatide, or a pharmaceutically acceptable salt thereof, for a minimum of about four weeks; and subsequently

[0073] d) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0074] In another aspect, the invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg ascending doses.

[0075] In another aspect, the present invention provides a method of improving glycemic control in a patient in need thereof, the method comprising:

[0076] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0077] b) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0078] c) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0079] d) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0080] e) administering to said patient increasing doses of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0081] f) administering to said patient a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0082] In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg ascending doses. In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 12.5 mg ascending doses. In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg and 12.5 mg ascending doses.

[0083] In another embodiment, is a method for treating type 2 diabetes in a patient in need thereof comprising administering tirzepatide, or a pharmaceutically acceptable salt thereof, in a tirzepatide dosage regimen comprising an escalation phase and a maintenance phase; wherein the escalation phase comprises administering 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for at least about 2 to 4 weeks; and wherein the maintenance phase comprises administering a dose of about 10 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly.

[0084] Additionally, the present invention provides a method for improving weight management in a patient in need thereof, the method comprising: administering an ascending dose about once a week for a minimum of about four weeks followed by at least one maintenance dose about once a week for a minimum of about four weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is an incremental increase of 2.5 mg relative to the ascending dose. An embodiment of the present invention is therefore a method for improving weight management, wherein the ascending dose administered about once a week for at least about four weeks is about 2.5 mg and the maintenance dose administered about once a week for at least about four weeks is about 5.0 mg. Another embodiment of the present invention is a method, wherein the ascending dose administered about once a week for at least about four weeks is about 7.5 mg and the maintenance dose administered about once a week for at least about four weeks is about 10.0 mg. Another embodiment of the present invention is a method wherein the incremental dose for at least about four weeks of approximately weekly administration is about 12.5 mg and the maintenance dose for at least about four weeks of approximately weekly administration is about 15.0 mg. Another embodiment of the present invention is wherein after the first maintenance dose has been administered for at least about four weeks, the second incremental dose is administered for at least about once a week for at least about four weeks and subsequently the second maintenance dose is administered for at least about once a week for at least about four weeks. Such a method therefore includes an incremental dose of about 2.5 mg and about 7.5 mg and a maintenance dose of about 5.0 mg and about 10.0 mg. Another embodiment of the present invention is wherein after the second maintenance dose has been administered for at least about four weeks, the third incremental dose is administered for at least about once a week for at least about four weeks and subsequently the third maintenance dose is administered for at least about once a week for at least about four weeks. Such a method therefore includes an incremental dose of about 2.5 mg, about 7.5 mg, and about 12.5 mg and a maintenance dose of about 5.0 mg, about 10.0 mg, and about 15.0 mg.

[0085] As indicated above, in certain embodiments of the present invention, if additional glycemic control is required, with or without intervening ascending doses, the maintenance dose can be increased to a subsequent maintenance dose. Thus, the present invention also provides a method of improving weight management in a patient in need thereof, comprising: administering ascending doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks, followed by a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks; and optionally thereafter, administering a second maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks; and optionally thereafter, administering a third maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0086] In another aspect, the present invention provides a method of improving weight management in a patient in need thereof, the method comprising:

[0087] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0088] b) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0089] 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 tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0090] Another embodiment provides a method of improving weight management in a patient in need thereof, the method comprising:

[0091] a) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0092] b) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0093] Another embodiment provides a method of improving weight management in a patient in need thereof, the method comprising:

[0094] a) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0095] b) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0096] 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 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0097] Another embodiment provides a method of improving weight management in a patient in need thereof, the method comprising:

[0098] a) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0099] b) administering to said patient a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0100] Another embodiment provides a method of improving weight management in a patient in need thereof, the method comprising:

[0101] a) administering to said patient increasing doses of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks; and

[0102] b) administering to said patient a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0103] 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 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once a week for a minimum of about four weeks.

[0104] In another aspect, the present invention provides a method of improving weight management in a patient in need thereof, the method comprising:

[0105] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0106] b) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0107] c) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0108] d) administering to the patient about 10.0 mg once about weekly for at least about four weeks of a maintenance dose of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0109] In another aspect, the present application includes a method as described in the preceding paragraphs, but the method does not include administering a 7.5 mg escalation dose.

[0110] In another aspect, the present application provides a method of improving glycemic control in a patient in need thereof, the method comprising:

[0111] a) administering to the patient about 2.5 mg once about weekly for at least about four weeks of an escalation dose of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0112] b) administering to the patient about 5.0 mg once about weekly for at least about four weeks of a maintenance dose of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0113] c) administering to the patient about 7.5 mg once about weekly for at least about four weeks of an escalation dose of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0114] d) administering to the patient about 10.0 mg once about weekly for at least about four weeks of a maintenance dose of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0115] e) administering to the patient about 12.5 mg once about weekly for at least about four weeks of an escalation dose of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0116] f) administering to the patient about 15.0 mg once about weekly for at least about four weeks of a maintenance dose of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0117] In another aspect, the present application includes a method as described in the preceding paragraphs, but the method does not include administering a 7.5 mg escalation dose. In another aspect, the present application includes a method as described in the preceding paragraphs, but the method does not include administering a 12.5 mg escalation dose. In another aspect, the present application includes a method as described in the preceding paragraphs, but the method does not include administering 7.5 mg and 12.5 mg escalation doses.

[0118] Additionally, the present invention provides a method of treating chronic kidney disease in a patient in need thereof, the method comprising administering an ascending dose about once a week for a minimum of about four weeks followed by a maintenance dose about once a week for a minimum of about four weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is an incremental increase of 2.5 mg relative to the ascending dose. An embodiment of the present invention is a method of treating chronic kidney disease, wherein the ascending dose administered about once a week for at least about four weeks is about 2.5 mg and the maintenance dose administered about once a week for at least about four weeks is about 5.0 mg. Another embodiment of the present invention is a method, wherein the ascending dose administered about once a week for at least about four weeks is about 7.5 mg and the maintenance dose administered about once a week for at least about four weeks is about 10.0 mg. Another embodiment of the invention is a method wherein the ascending dose for approximately weekly administration for at least about four weeks is about 12.5 mg and the maintenance dose for approximately weekly administration for at least about four weeks is about 15.0 mg. Another embodiment of the invention is wherein the ascending dose for approximately weekly administration for at least about four weeks is about 2.5 mg and about 7.5 mg and the maintenance dose for approximately weekly administration for at least about four weeks is about 5.0 mg and about 10.0 mg. Another embodiment of the invention is wherein the ascending dose for approximately weekly administration for at least about four weeks is about 2.5 mg, about 5.0 mg, and about 7.5 mg and the maintenance dose for approximately weekly administration for at least about four weeks is about 5.0 mg, about 10.0 mg, and about 15.0 mg.

[0119] Accordingly, the present invention provides a method of treating chronic kidney disease in a patient in need thereof, the method comprising:

[0120] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0121] b) administering to said patient about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0122] In another aspect, the present invention provides a method of treating chronic kidney disease 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 about once a week for a minimum of about four weeks.

[0123] Another embodiment provides a method of treating chronic kidney disease in a patient in need thereof, the method comprising:

[0124] a) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0125] b) administering to said patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0126] Another embodiment provides a method of treating chronic kidney disease in a patient in need thereof, the method comprising:

[0127] a) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0128] b) administering to said patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0129] In another aspect, the present invention provides a method of treating chronic kidney disease in a patient in need thereof, comprising administering to the patient a maintenance dose of about 10.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

[0130] Another embodiment provides a method of treating chronic kidney disease in a patient in need thereof, the method comprising:

[0131] a) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0132] b) administering to said patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0133] Another embodiment provides a method of treating chronic kidney disease in a patient in need thereof, the method comprising:

[0134] a) administering to said patient increasing doses of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0135] b) administering to said patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0136] In another aspect, the present application provides a method for treating chronic kidney disease in a patient in need thereof, comprising: administering to the patient about 15.0 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0137] In another aspect, the present application provides a method for treating chronic kidney disease in a patient in need thereof, comprising:

[0138] a) administering to the patient about 2.5 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0139] b) administering to the patient about 5.0 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0140] c) administering to the patient about 7.5 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0141] d) administering to the patient about 10.0 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0142] In another aspect, the present application includes a method as described in the preceding paragraphs, but the method does not include administering a 7.5 mg escalation dose.

[0143] In another aspect, the present application provides a method for treating chronic kidney disease in a patient in need thereof, comprising:

[0144] a) administering to the patient about 2.5 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0145] b) administering to the patient about 5.0 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0146] c) administering to the patient about 7.5 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0147] d) administering to the patient about 10.0 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0148] e) administering to the patient about 12.5 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0149] f) administering to said patient a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0150] In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg ascending doses. In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 12.5 mg ascending doses. In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg and 12.5 mg ascending doses.

[0151] In another embodiment, is a method of treating diabetic kidney disease in a patient in need thereof, comprising: administering an ascending dose about once per week for a minimum of about four weeks, followed by administering a maintenance dose about once per week for a minimum of about four weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is an incremental increase of 2.5 mg relative to the ascending dose.

[0152] Also, the present application provides for a method of treating atherosclerosis in a patient in need thereof comprising administering an escalation dose once about weekly for a minimum of about four weeks and thereafter administering a maintenance dose once about weekly for a minimum of about four weeks; wherein the escalation 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; wherein 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 wherein the maintenance dose following the escalation dose is a 2.5 mg incremental increase over the escalation dose. An embodiment of the present application is a method of treating atherosclerosis wherein the escalation dose administered once about weekly for a minimum of about four weeks is about 2.5 mg and the maintenance dose administered once about weekly for a minimum of about four weeks is about 5.0 mg. Another embodiment of the present application is a method wherein the escalation dose administered once about weekly for a minimum of about four weeks is about 7.5 mg and the maintenance dose administered once about weekly for a minimum of about four weeks is about 10.0 mg. Another embodiment of the present application is a method wherein the escalation dose administered once about weekly for a minimum of about four weeks is about 12.5 mg and the maintenance dose administered once about weekly for a minimum of about four weeks is about 15.0 mg. Another embodiment of the present application is a method wherein the escalation dose administered once about weekly for a minimum of about four weeks is about 2.5 mg and about 7.5 mg and the maintenance dose administered once about weekly for a minimum of about four weeks is about 5.0 mg and about 10.0 mg. Another embodiment of the present application is a method wherein the escalation dose administered once about weekly for a minimum of about four weeks is about 2.5 mg, about 5.0 mg, and about 7.5 mg and the maintenance dose administered once about weekly for a minimum of about four weeks is about 5.0 mg, about 10.0 mg, and about 15.0 mg.

[0153] In another aspect, the present application provides a method of treating atherosclerosis in a patient in need thereof comprising:

[0154] a) administering to the patient about 2.5 mg of an escalation dose of tirzepatide, or a pharmaceutically acceptable salt thereof, once about weekly for a minimum of about four weeks; and thereafter

[0155] b) administering to the patient about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, once about weekly for a minimum of about four weeks.

[0156] In another aspect, the present application provides a method of treating atherosclerosis in a patient in need thereof comprising: administering to the patient about 5.0 mg of a maintenance dose of tirzepatide, or a pharmaceutically acceptable salt thereof, once about weekly for a minimum of about four weeks.

[0157] Another embodiment provides a method of treating atherosclerosis in a patient in need thereof, the method comprising:

[0158] a) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0159] b) administering to said patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0160] Another embodiment provides a method of treating atherosclerosis in a patient in need thereof, the method comprising:

[0161] a) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0162] b) administering to said patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0163] In another aspect, the present invention provides a method of treating atherosclerosis in a patient in need thereof, comprising administering to the patient a maintenance dose of about 10.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

[0164] Another embodiment provides a method of treating atherosclerosis in a patient in need thereof, the method comprising:

[0165] a) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0166] b) administering to said patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0167] Another embodiment provides a method of treating atherosclerosis in a patient in need thereof, the method comprising:

[0168] a) administering to said patient increasing doses of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0169] b) administering to said patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0170] In another aspect, the present invention provides a method of treating atherosclerosis in a patient in need thereof, the method comprising:

[0171] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0172] b) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0173] c) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0174] d) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0175] In another aspect, the invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg ascending doses.

[0176] In another aspect, the present invention provides a method of treating atherosclerosis in a patient in need thereof, the method comprising:

[0177] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0178] b) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0179] c) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0180] d) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0181] e) administering to said patient increasing doses of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0182] f) administering to said patient a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0183] In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg ascending doses. In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 12.5 mg ascending doses. In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg and 12.5 mg ascending doses.

[0184] In addition, the present invention provides a method for treating NAFLD in a patient in need thereof, the method comprising administering an ascending dose about once a week for a minimum of about four weeks and subsequently administering a maintenance dose about once a week for a minimum of about four weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose after the ascending dose is an incremental increase of 2.5 mg relative to the ascending dose. An embodiment of the present invention is a method for treating NAFLD, wherein the ascending dose administered about once a week for at least about four weeks is about 2.5 mg and the maintenance dose administered about once a week for at least about four weeks is about 5.0 mg. Another embodiment of the present invention is a method, wherein the ascending dose administered about once a week for at least about four weeks is about 7.5 mg and the maintenance dose administered about once a week for at least about four weeks is about 10.0 mg. Another embodiment of the invention is a method wherein the ascending dose for approximately weekly administration for at least about four weeks is about 12.5 mg and the maintenance dose for approximately weekly administration for at least about four weeks is about 15.0 mg. Another embodiment of the invention is wherein the ascending dose for approximately weekly administration for at least about four weeks is about 2.5 mg and about 7.5 mg and the maintenance dose for approximately weekly administration for at least about four weeks is about 5.0 mg and about 10.0 mg. Another embodiment of the invention is wherein the ascending dose for approximately weekly administration for at least about four weeks is about 2.5 mg, about 5.0 mg, and about 7.5 mg and the maintenance dose for approximately weekly administration for at least about four weeks is about 5.0 mg, about 10.0 mg, and about 15.0 mg.

[0185] Therefore, the present invention provides a method of treating NAFLD in a patient in need thereof, the method comprising:

[0186] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0187] b) administering to the patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0188] In another aspect, the present application provides a method of treating NAFLD in a patient in need thereof comprising: administering to the patient about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a maintenance dose for a minimum of about four weeks.

[0189] Another embodiment provides a method of treating NAFLD in a patient in need thereof comprising:

[0190] a) administering to the patient about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a maintenance dose for a minimum of about four weeks; and subsequently

[0191] b) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0192] Another embodiment provides a method of treating NAFLD in a patient in need thereof comprising:

[0193] a) administering to the patient about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for an escalation dose for a minimum of about four weeks; and subsequently

[0194] b) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0195] In another aspect, the present application provides a method of treating NAFLD in a patient in need thereof comprising: administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a maintenance dose for a minimum of about four weeks.

[0196] Another embodiment provides a method of treating NAFLD in a patient in need thereof comprising:

[0197] a) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a maintenance dose for a minimum of about four weeks; and subsequently

[0198] b) administering to the patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0199] Another embodiment provides a method of treating NAFLD in a patient in need thereof comprising:

[0200] a) administering to said patient increasing doses of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0201] b) administering to said patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0202] In another aspect, the present invention provides a method of treating NAFLD in a patient in need thereof, comprising administering to the patient a dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once a week for a minimum of about four weeks.

[0203] In another aspect, the present invention provides a method of treating NAFLD in a patient in need thereof, the method comprising:

[0204] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0205] b) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0206] c) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0207] d) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0208] In another aspect, the invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg ascending doses.

[0209] In another aspect, the present invention provides a method of treating NAFLD in a patient in need thereof, the method comprising:

[0210] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0211] b) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0212] c) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0213] d) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0214] e) administering to said patient increasing doses of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0215] f) administering to said patient a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0216] In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg ascending doses. In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 12.5 mg ascending doses. In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg and 12.5 mg ascending doses.

[0217] In one embodiment, is a method of treating dyslipidemia in a patient in need thereof, comprising: administering an ascending dose about once per week for a minimum of about four weeks, followed by administering a maintenance dose about once per week for a minimum of about four weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is an incremental increase of 2.5 mg relative to the ascending dose.

[0218] Additionally, the present invention provides a method of treating NASH in a patient in need thereof, the method comprising administering an ascending dose about once a week for a minimum of about four weeks followed by a maintenance dose about once a week for a minimum of about four weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is an incremental increase of 2.5 mg relative to the ascending dose. An embodiment of the present invention is a method of treating NASH, wherein the ascending dose administered about once a week for at least about four weeks is about 2.5 mg and the maintenance dose administered about once a week for at least about four weeks is about 5.0 mg. Another embodiment of the present invention is a method, wherein the ascending dose administered about once a week for at least about four weeks is about 7.5 mg and the maintenance dose administered about once a week for at least about four weeks is about 10.0 mg. Another embodiment of the invention is a method wherein the ascending dose for approximately weekly administration for at least about four weeks is about 12.5 mg and the maintenance dose for approximately weekly administration for at least about four weeks is about 15.0 mg. Another embodiment of the invention is wherein the ascending dose for approximately weekly administration for at least about four weeks is about 2.5 mg and about 7.5 mg and the maintenance dose for approximately weekly administration for at least about four weeks is about 5.0 mg and about 10.0 mg. Another embodiment of the invention is wherein the ascending dose for approximately weekly administration for at least about four weeks is about 2.5 mg, about 5.0 mg, and about 7.5 mg and the maintenance dose for approximately weekly administration for at least about four weeks is about 5.0 mg, about 10.0 mg, and about 15.0 mg.

[0219] Therefore, the present invention provides a method of treating NASH in a patient in need thereof, the method comprising:

[0220] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0221] b) administering to said patient about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0222] In another aspect, the present invention provides a method of treating NASH 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, about once a week for a minimum of about four weeks.

[0223] Another embodiment provides a method of treating NASH in a patient in need thereof, the method comprising:

[0224] a) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0225] b) administering to said patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0226] Another embodiment provides a method of treating NASH in a patient in need thereof, the method comprising:

[0227] a) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0228] b) administering to said patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0229] In another aspect, the present invention provides a method of treating NASH in a patient in need thereof, comprising administering to the patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once a week for a minimum of about four weeks.

[0230] Another embodiment provides a method of treating NASH in a patient in need thereof, the method comprising:

[0231] a) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0232] b) administering to said patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0233] Another embodiment provides a method of treating NASH in a patient in need thereof, the method comprising:

[0234] a) administering to said patient increasing doses of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0235] b) administering to said patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0236] In another aspect, the present invention provides a method of treating NASH in a patient in need thereof, comprising administering to the patient a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once a week for a minimum of about four weeks.

[0237] In another aspect, the present invention provides a method of treating NASH in a patient in need thereof, the method comprising:

[0238] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0239] b) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0240] c) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0241] d) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0242] In another aspect, the invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg ascending doses.

[0243] In another aspect, the present invention provides a method of treating NASH in a patient in need thereof, the method comprising:

[0244] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0245] b) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0246] c) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0247] d) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0248] e) administering to said patient increasing doses of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0249] f) administering to said patient a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0250] In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg ascending doses. In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 12.5 mg ascending doses. In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg and 12.5 mg ascending doses.

[0251] In addition, the present invention provides a method for curing diabetes, causing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, the method comprising administering an ascending dose about once a week for a minimum of about four weeks followed by a maintenance dose about once a week for a minimum of about four weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is an incremental increase of 2.5 mg relative to the ascending dose. An embodiment of the present invention is a method for curing diabetes, causing remission or regression of diabetes, or preventing diabetes, wherein the ascending dose administered about once a week for at least about four weeks is about 2.5 mg and the maintenance dose administered about once a week for at least about four weeks is about 5.0 mg. Another embodiment of the present invention is a method wherein the ascending dose administered about once a week for at least about four weeks is about 7.5 mg and the maintenance dose administered about once a week for at least about four weeks is about 10.0 mg. Another embodiment of the invention is a method wherein the ascending dose for approximately weekly administration for at least about four weeks is about 12.5 mg and the maintenance dose for approximately weekly administration for at least about four weeks is about 15.0 mg. Another embodiment of the invention is wherein the ascending dose for approximately weekly administration for at least about four weeks is about 2.5 mg and about 7.5 mg and the maintenance dose for approximately weekly administration for at least about four weeks is about 5.0 mg and about 10.0 mg. Another embodiment of the invention is wherein the ascending dose for approximately weekly administration for at least about four weeks is about 2.5 mg, about 5.0 mg, and about 7.5 mg and the maintenance dose for approximately weekly administration for at least about four weeks is about 5.0 mg, about 10.0 mg, and about 15.0 mg.

[0252] Therefore, the present invention provides a method for curing diabetes, causing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, the method comprising:

[0253] a) administering to the patient about once a week for at least about four weeks an escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0254] b) administering to the patient about once a week for at least about four weeks about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0255] In another aspect, the present application provides a method for curing, inducing remission or causing regression of, or preventing diabetes mellitus in a patient in need thereof, comprising: administering to the patient about once a week for at least about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0256] Another embodiment provides a method for curing, inducing remission or causing regression of, or preventing diabetes mellitus in a patient in need thereof, comprising:

[0257] a) administering to the patient about once a week for at least about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0258] b) administering to the patient about once a week for at least about four weeks about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0259] Another embodiment provides a method for curing, inducing remission or causing regression of, or preventing diabetes mellitus in a patient in need thereof, comprising:

[0260] a) administering to the patient about once a week for at least about four weeks an escalation dose of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0261] b) administering to the patient about once a week for at least about four weeks about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0262] In another aspect, the present application provides a method for curing, inducing remission or causing regression of, or preventing diabetes mellitus in a patient in need thereof, comprising: administering to the patient about once a week for at least about four weeks a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0263] Another embodiment provides a method for curing, inducing remission or causing regression of, or preventing diabetes mellitus in a patient in need thereof, comprising:

[0264] a) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and subsequently

[0265] b) administering to the patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0266] Another embodiment provides a method of curing, inducing remission or causing regression of diabetes, or preventing diabetes in a patient in need thereof, comprising:

[0267] a) administering to the patient about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and subsequently

[0268] b) administering to the patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0269] In another aspect, the present application provides a method of curing, inducing remission or causing regression of diabetes, or preventing diabetes in a patient in need thereof, comprising: administering to the patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0270] In another aspect, the present application provides a method of curing, inducing remission or causing regression of diabetes, or preventing diabetes in a patient in need thereof, comprising:

[0271] a) administering to the patient about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and subsequently

[0272] b) administering to the patient about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and subsequently

[0273] c) administering to the patient about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and subsequently

[0274] d) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0275] In another aspect, the present application includes a method as described in the preceding paragraphs, but the method does not include administering a 7.5 mg escalation dose.

[0276] In another aspect, the present invention provides a method of curing diabetes, causing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, the method comprising:

[0277] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0278] b) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0279] c) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0280] d) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0281] e) administering to said patient increasing doses of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0282] f) administering to said patient a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0283] In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg ascending doses. In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 12.5 mg ascending doses. In another aspect, the present invention includes a method as described in the preceding paragraph, but the method does not include administering 7.5 mg and 12.5 mg ascending doses.

[0284] Additionally, the present invention provides a use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for treating type 2 diabetes in a patient in need thereof, comprising: administering an ascending dose about once a week for a minimum of about four weeks followed by administering a maintenance dose about once a week for a minimum of about four weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is an incremental increase of 2.5 mg relative to the ascending dose.

[0285] The present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating type 2 diabetes in a patient in need thereof comprising:

[0286] a) administering to the patient about once a week for at least about four weeks an escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0287] b) administering to the patient about once a week for at least about four weeks about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0288] In another aspect, the present application provides the use of tirzepatide, 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 about once a week for at least about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0289] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating type 2 diabetes in a patient in need thereof comprising:

[0290] a) administering to the patient about once a week for at least about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0291] b) administering to the patient about once a week for at least about four weeks about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0292] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating type 2 diabetes in a patient in need thereof comprising:

[0293] a) administering to the patient about once a week for at least about four weeks an escalation dose of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0294] b) administering to the patient about once a week for at least about four weeks about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0295] In another aspect, the present application provides the use of tirzepatide, 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 about once a week for at least about four weeks a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0296] Another embodiment provides the use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating type 2 diabetes in a patient in need thereof, comprising:

[0297] a) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0298] b) administering to said patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0299] Another embodiment provides the use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating type 2 diabetes in a patient in need thereof, comprising:

[0300] a) administering to said patient increasing doses of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0301] b) administering to said patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0302] In another aspect, the present invention provides a use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation 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 tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

[0303] In another aspect, the present invention provides use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating type 2 diabetes in a patient in need thereof, comprising:

[0304] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0305] b) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0306] c) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0307] d) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0308] In another aspect, the present application includes the use of medicaments as described in the preceding paragraphs, but the use of medicaments does not include administration of a 7.5 mg escalation dose.

[0309] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating type 2 diabetes in a patient in need thereof, comprising:

[0310] a) administering to the patient about once a week for a minimum of about four weeks an escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0311] b) administering to the patient about once a week for a minimum of about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0312] c) administering to the patient about once a week for a minimum of about four weeks an escalation dose of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0313] d) administering to the patient about once a week for a minimum of about four weeks a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0314] e) administering to the patient about once a week for a minimum of about four weeks an escalation dose of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0315] f) administering to the patient about once a week for a minimum of about four weeks a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0316] In another aspect, the present application includes the use of medicaments as described in the preceding paragraphs, but the use of medicaments does not include administration of a 7.5 mg escalation dose. In another aspect, the present application includes the use of medicaments as described in the preceding paragraphs, but the use of medicaments does not include administration of a 12.5 mg escalation dose. In another aspect, the present application includes the use of medicaments as described in the preceding paragraphs, but the use of medicaments does not include administration of 7.5 mg and 12.5 mg escalation doses.

[0317] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving glycemic control in a patient in need thereof, comprising: administering to the patient about once a week for a minimum of about four weeks an escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently administering to the patient about once a week for a minimum of about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0318] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving glycemic control in a patient in need thereof, comprising:

[0319] a) administering to the patient about once a week for a minimum of about four weeks an escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0320] b) administering to the patient about once a week for a minimum of about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0321] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving glycemic control in a patient in need thereof, comprising: administering to the patient about once a week for a minimum of about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0322] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving glycemic control in a patient in need thereof, comprising:

[0323] a) administering to the patient about once a week for a minimum of about four weeks an escalation dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0324] b) administering to the patient about once a week for a minimum of about four weeks a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0325] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving glycemic control in a patient in need thereof, comprising:

[0326] a) administering to the patient about once a week for a minimum of about four weeks an escalation dose of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0327] b) administering to said patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0328] In another aspect, the present invention provides a use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for improving glycemic control in a patient in need thereof, comprising administering to the patient a maintenance dose of about 10.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

[0329] Another embodiment provides the use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for improving glycemic control in a patient in need thereof, comprising:

[0330] a) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0331] b) administering to said patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0332] Another embodiment provides the use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for improving glycemic control in a patient in need thereof, comprising:

[0333] a) administering to said patient increasing doses of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0334] b) administering to said patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0335] In another aspect, the present invention provides a use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for improving glycemic control in a patient in need thereof, comprising: administering to the patient a maintenance dose of about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

[0336] In another aspect, the present invention provides a use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for improving glycemic control in a patient in need thereof, comprising:

[0337] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0338] b) administering to the patient about once a week for at least about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0339] c) administering to the patient about once a week for at least about four weeks an escalation dose of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0340] d) administering to the patient about once a week for at least about four weeks a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0341] In another aspect, the present application includes the use of medicaments as described in the preceding paragraphs, but the use of medicaments does not include administration of a 7.5 mg escalation dose.

[0342] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving glycemic control in a patient in need thereof, comprising:

[0343] a) administering to the patient about once a week for at least about four weeks an escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0344] b) administering to the patient about once a week for at least about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0345] c) administering to the patient about once a week for at least about four weeks an escalation dose of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0346] d) administering to the patient about once a week for at least about four weeks a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0347] e) administering to the patient about once a week for at least about four weeks an escalation dose of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0348] f) administering to the patient about once a week for at least about four weeks a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0349] In another aspect, the present application includes the use of medicaments as described in the preceding paragraphs, but the use of medicaments does not include administration of a 7.5 mg escalation dose. In another aspect, the present application includes the use of medicaments as described in the preceding paragraphs, but the use of medicaments does not include administration of a 12.5 mg escalation dose. In another aspect, the present application includes the use of medicaments as described in the preceding paragraphs, but the use of medicaments does not include administration of 7.5 mg and 12.5 mg escalation doses.

[0350] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving weight management in a patient in need thereof comprising: administering to the patient about once a week for a minimum of about four weeks an escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently administering to the patient about once a week for a minimum of about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0351] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving weight management in a patient in need thereof comprising:

[0352] a) administering to the patient about once a week for a minimum of about four weeks an escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0353] b) administering to the patient about once a week for a minimum of about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0354] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving weight management in a patient in need thereof comprising: administering to the patient about once a week for a minimum of about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0355] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving weight management in a patient in need thereof comprising:

[0356] a) administering to the patient about once a week for a minimum of about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0357] b) administering to the patient about once a week for a minimum of about four weeks a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0358] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving weight management in a patient in need thereof comprising:

[0359] a) administering to the patient about once a week for a minimum of about four weeks an escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0360] b) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0361] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving glycemic control in a patient in need thereof comprising: administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0362] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving glycemic control in a patient in need thereof comprising:

[0363] a) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks as a maintenance dose; and subsequently

[0364] b) administering to the patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0365] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving glycemic control in a patient in need thereof comprising:

[0366] a) administering to the patient about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks as a titration dose; and subsequently

[0367] b) administering to the patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0368] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving glycemic control in a patient in need thereof comprising: administering to the patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks as a maintenance dose.

[0369] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving glycemic control in a patient in need thereof comprising:

[0370] a) administering to the patient about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks as a titration dose; and subsequently

[0371] b) administering to the patient about once a week for at least about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0372] c) administering to the patient about once a week for at least about four weeks an escalation dose of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0373] d) administering to the patient about once a week for at least about four weeks a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0374] In another aspect, the present application includes the use of medicaments as described in the preceding paragraphs, but the use of medicaments does not include administration of a 7.5 mg escalation dose.

[0375] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for improving glycemic control in a patient in need thereof, comprising:

[0376] a) administering to the patient about once a week for at least about four weeks an escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0377] b) administering to the patient about once a week for at least about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0378] c) administering to the patient about once a week for at least about four weeks an escalation dose of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0379] d) administering to the patient about once a week for at least about four weeks a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0380] e) administering to the patient about once a week for at least about four weeks an escalation dose of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0381] f) administering to the patient about once a week for at least about four weeks a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0382] In another aspect, the present application includes the use of medicaments as described in the preceding paragraphs, but the use of medicaments does not include administration of a 7.5 mg escalation dose. In another aspect, the present application includes the use of medicaments as described in the preceding paragraphs, but the use of medicaments does not include administration of a 12.5 mg escalation dose. In another aspect, the present application includes the use of medicaments as described in the preceding paragraphs, but the use of medicaments does not include administration of 7.5 mg and 12.5 mg escalation doses.

[0383] Additionally, the present invention provides use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for treating chronic kidney disease in a patient in need thereof, comprising: administering an ascending dose about once a week for a minimum of about four weeks followed by administering a maintenance dose about once a week for a minimum of about four weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is an incremental increase of 2.5 mg relative to the ascending dose.

[0384] The present invention provides use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating chronic kidney disease in a patient in need thereof, comprising:

[0385] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0386] b) administering to said patient about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0387] In another aspect, the present invention provides a use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating chronic kidney disease 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 about once a week for a minimum of about four weeks.

[0388] Another embodiment provides the use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating chronic kidney disease in a patient in need thereof, comprising:

[0389] a) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0390] b) administering to said patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0391] Another embodiment provides the use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating chronic kidney disease in a patient in need thereof, comprising:

[0392] a) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0393] b) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for at least about four weeks.

[0394] In another aspect, the application provides the use of tirzepatide, 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 about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, as a maintenance dose about once weekly for at least about four weeks.

[0395] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating chronic kidney disease in a patient in need thereof comprising:

[0396] a) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, as a maintenance dose about once weekly for at least about four weeks; and subsequently

[0397] b) administering to the patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for at least about four weeks.

[0398] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating chronic kidney disease in a patient in need thereof comprising:

[0399] a) administering to the patient about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, as an escalation dose about once weekly for at least about four weeks; and subsequently

[0400] b) administering to the patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for at least about four weeks.

[0401] In another aspect, the application provides the use of tirzepatide, 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 about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, as a maintenance dose about once weekly for at least about four weeks.

[0402] In another aspect, the application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating chronic kidney disease in a patient in need thereof comprising:

[0403] a) administering to the patient about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, as an escalation dose about once weekly for at least about four weeks; and subsequently

[0404] b) administering to the patient about once a week for at least about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0405] c) administering to the patient about once a week for at least about four weeks an escalation dose of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0406] d) administering to the patient about once a week for at least about four weeks a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0407] In another aspect, the present application includes the use of medicaments as described in the preceding paragraphs, but the use of medicaments does not include administration of a 7.5 mg escalation dose.

[0408] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating chronic kidney disease in a patient in need thereof, comprising:

[0409] a) administering to the patient about once a week for at least about four weeks an escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0410] b) administering to the patient about once a week for at least about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0411] c) administering to the patient about once a week for at least about four weeks an escalation dose of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0412] d) administering to the patient about once a week for at least about four weeks a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0413] e) administering to the patient about once a week for at least about four weeks an escalation dose of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0414] f) administering to the patient about once a week for at least about four weeks a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0415] In another aspect, the present application includes the use of medicaments as described in the preceding paragraphs, but the use of medicaments does not include administration of a 7.5 mg escalation dose. In another aspect, the present application includes the use of medicaments as described in the preceding paragraphs, but the use of medicaments does not include administration of a 12.5 mg escalation dose. In another aspect, the present application includes the use of medicaments as described in the preceding paragraphs, but the use of medicaments does not include administration of 7.5 mg and 12.5 mg escalation doses.

[0416] In another embodiment, the present invention provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for treating diabetic kidney disease in a patient in need thereof, comprising: administering an ascending dose about once a week for a minimum of about four weeks followed by administering a maintenance dose about once a week for a minimum of about four weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is an incremental increase of 2.5 mg relative to the ascending dose.

[0417] Additionally, the present invention provides a use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating atherosclerosis in a patient in need thereof, comprising: administering an ascending dose about once a week for a minimum of about four weeks followed by a maintenance dose about once a week for a minimum of about four weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is an incremental increase of 2.5 mg relative to the ascending dose.

[0418] In addition, the present invention provides a use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating atherosclerosis in a patient in need thereof, comprising:

[0419] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0420] b) administering to said patient about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0421] In another aspect, the present invention provides a use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation 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 tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

[0422] Another embodiment provides the use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating atherosclerosis in a patient in need thereof, comprising:

[0423] a) administering to the patient about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and subsequently

[0424] b) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0425] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating atherosclerosis in a patient in need thereof, comprising:

[0426] a) administering to the patient about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and subsequently

[0427] b) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0428] In another aspect, the present application provides the use of tirzepatide, 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 about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0429] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating atherosclerosis in a patient in need thereof, comprising:

[0430] a) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and subsequently

[0431] b) administering to the patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0432] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating atherosclerosis in a patient in need thereof, comprising:

[0433] a) administering to the patient about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and

[0434] b) administering to the patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0435] In another aspect, the present application provides the use of tirzepatide, 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 about 15.0 mg once weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0436] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating atherosclerosis in a patient in need thereof, comprising:

[0437] a) administering to the patient about 2.5 mg once weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0438] b) administering to the patient about 5.0 mg once weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0439] c) administering to the patient about 7.5 mg once weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0440] d) administering to the patient about 10.0 mg once weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0441] In another aspect, the present application includes the uses as described in the preceding paragraphs, but wherein the use does not include administration of a 7.5 mg escalation dose.

[0442] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating atherosclerosis in a patient in need thereof, comprising:

[0443] a) administering to the patient about 2.5 mg once weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0444] b) administering to the patient about 5.0 mg once weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0445] c) administering to the patient about 7.5 mg once weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0446] d) administering to the patient about 10.0 mg once weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0447] e) administering to the patient about once a week for a minimum of about four weeks an escalation dose of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and thereafter

[0448] f) administering to the patient about once a week for a minimum of about four weeks a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0449] In another aspect, the present application includes the use as described in the preceding paragraph, but the use does not include administration of a 7.5 mg escalation dose. In another aspect, the present application includes the use as described in the preceding paragraph, but the use does not include administration of a 12.5 mg escalation dose. In another aspect, the present application includes the use as described in the preceding paragraph, but the use does not include administration of 7.5 mg and 12.5 mg escalation doses.

[0450] In one embodiment is a method of treating dyslipidemia in a patient in need thereof comprising: administering an escalation dose about once a week for a minimum of at least about two weeks and thereafter administering a maintenance dose about once a week for a minimum of at least about two weeks; wherein the escalation dose is selected from the group consisting of about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein 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.

[0451] In one embodiment is a method for treating dyslipidemia in a patient in need thereof comprising: administering at least one escalation dose about once a week for a minimum of about four weeks and administering at least one maintenance dose about once a week for a minimum of about four weeks after the escalation dose; wherein the escalation 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; wherein 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 wherein the maintenance dose after the escalation dose is an escalation of 2.5 mg.

[0452] In one embodiment is a method of treating dyslipidemia wherein the escalation dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

[0453] In one embodiment is a method of treating dyslipidemia wherein the escalation dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

[0454] In one embodiment is a method of treating dyslipidemia wherein the escalation dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

[0455] In one embodiment is a method for treating dyslipidemia, further comprising a escalation dose of about 7.5 mg and a maintenance dose of about 10.0 mg.

[0456] In one embodiment is a method for treating dyslipidemia, further comprising a escalation dose of about 12.5 mg and a maintenance dose of about 15.0 mg.

[0457] In one embodiment is a method for treating dyslipidemia, wherein the patient in need of such treatment does not have a co-morbid Type 1 or Type 2 diabetes.

[0458] Also provided is the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NALFD in a patient in need thereof comprising: administering a escalation dose about once weekly for a minimum of about four weeks and thereafter administering a maintenance dose about once weekly for a minimum of about four weeks; wherein the escalation 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; wherein 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 wherein the maintenance dose following the escalation dose is a 2.5 mg incremental increase relative to the escalation dose.

[0459] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NAFLD in a patient in need thereof comprising:

[0460] a) administering to said patient a escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0461] b) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0462] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NAFLD in a patient in need thereof comprising: administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0463] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NAFLD in a patient in need thereof comprising:

[0464] a) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0465] b) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for at least about four weeks.

[0466] Another embodiment provides use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NAFLD in a patient in need thereof, comprising:

[0467] a) administering to the patient about a 7.5 mg escalation dose of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for at least about four weeks; and subsequently

[0468] b) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for at least about four weeks.

[0469] In another aspect, the present application provides use of tirzepatide, 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 about a 10.0 mg maintenance dose of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for at least about four weeks.

[0470] Another embodiment provides use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NAFLD in a patient in need thereof, comprising:

[0471] a) administering to the patient about a 10.0 mg maintenance dose of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for at least about four weeks; and subsequently

[0472] b) administering to the patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for at least about four weeks.

[0473] Another embodiment provides use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NAFLD in a patient in need thereof, comprising:

[0474] a) administering to the patient about a 12.5 mg escalation dose of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for at least about four weeks; and subsequently

[0475] b) administering to the patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for at least about four weeks.

[0476] In another aspect, the present invention provides a use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating NAFLD in a patient in need thereof, comprising administering to the patient a maintenance dose of about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

[0477] In another aspect, the present invention provides a use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating NAFLD in a patient in need thereof, comprising:

[0478] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0479] b) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0480] c) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0481] d) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0482] In another aspect, the invention comprises a use as described in the preceding paragraph, but said use does not comprise administering 7.5 mg ascending doses.

[0483] In another aspect, the present invention provides a use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating NAFLD in a patient in need thereof, comprising:

[0484] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0485] b) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0486] c) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0487] d) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0488] e) administering to said patient about once a week for a minimum of about four weeks an escalation dose of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0489] f) administering to said patient about once a week for a minimum of about four weeks a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0490] In another aspect, the present application includes the use of medicaments as described in the preceding paragraph, but said use of medicaments does not include administration of a 7.5 mg escalation dose. In another aspect, the present application includes the use of medicaments as described in the preceding paragraph, but said use of medicaments does not include administration of a 12.5 mg escalation dose. In another aspect, the present application includes the use of medicaments as described in the preceding paragraph, but said use of medicaments does not include administration of 7.5 mg and 12.5 mg escalation doses.

[0491] Further, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NASH in a patient in need thereof, comprising: administering an escalation dose about once a week for a minimum of about four weeks and subsequently administering a maintenance dose about once a week for a minimum of about four weeks; wherein the escalation 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; wherein 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 wherein the maintenance dose following an escalation dose is a 2.5 mg incremental increase relative to that escalation dose.

[0492] The present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NASH in a patient in need thereof, comprising:

[0493] a) administering to said patient about once a week for a minimum of about four weeks an escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0494] b) administering to said patient about once a week for a minimum of about four weeks about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0495] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NASH in a patient in need thereof, comprising: administering to said patient about once a week for a minimum of about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0496] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NASH in a patient in need thereof, comprising: Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NASH in a patient in need thereof, comprising:

[0497] a) administering to the patient about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and subsequently

[0498] b) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0499] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NASH in a patient in need thereof, comprising:

[0500] a) administering to the patient about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and subsequently

[0501] b) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0502] In another aspect, the present application provides the use of tirzepatide, 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 about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0503] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NASH in a patient in need thereof, comprising:

[0504] a) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and subsequently

[0505] b) administering to the patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0506] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NASH in a patient in need thereof, comprising:

[0507] a) administering to the patient about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and subsequently

[0508] b) administering to the patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0509] In another aspect, the present application provides the use of tirzepatide, 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 about 15.0 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof, and thereafter

[0510] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NASH in a patient in need thereof comprising:

[0511] a) administering to the patient about 2.5 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof, and thereafter

[0512] b) administering to the patient about 5.0 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof, and thereafter

[0513] c) administering to the patient about 7.5 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof, and thereafter

[0514] d) administering to the patient about 10.0 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0515] In another aspect, the present application includes the uses as described in the preceding paragraphs, but wherein the medicaments do not include administration of a 7.5 mg escalation dose.

[0516] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating NASH in a patient in need thereof comprising:

[0517] a) administering to the patient about 2.5 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof, and thereafter

[0518] b) administering to the patient about 5.0 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof, and thereafter

[0519] c) administering to the patient about 7.5 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof, and thereafter

[0520] d) administering to the patient about 10.0 mg once about weekly for at least about four weeks of tirzepatide, or a pharmaceutically acceptable salt thereof, and thereafter

[0521] e) administering to said patient increasing doses of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0522] f) administering to said patient a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0523] In another aspect, the present invention comprises the use as described in the preceding paragraph, but the use does not include administering 7.5 mg ascending doses. In another aspect, the present invention comprises the use as described in the preceding paragraph, but the use does not include administering 12.5 mg ascending doses. In another aspect, the present invention comprises the use as described in the preceding paragraph, but the use does not include administering 7.5 mg and 12.5 mg ascending doses.

[0524] Additionally, the present invention provides a use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for curing diabetes, causing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, comprising: administering an ascending dose about once a week for a minimum of about four weeks followed by a maintenance dose about once a week for a minimum of about four weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is an incremental increase of 2.5 mg relative to the ascending dose.

[0525] The present invention provides the use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for curing diabetes, causing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, comprising:

[0526] a) administering to said patient increasing doses of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0527] b) administering to said patient about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0528] In another aspect, the present invention provides the use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for curing diabetes, causing 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 tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

[0529] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for curing, inducing remission of, causing regression of, or preventing diabetes in a patient in need thereof comprising:

[0530] a) administering to the patient about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and subsequently

[0531] b) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0532] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for curing, inducing remission of, causing regression of, or preventing diabetes in a patient in need thereof comprising:

[0533] a) administering to the patient about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and subsequently

[0534] b) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0535] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for curing, inducing remission of, causing regression of, or preventing diabetes in a patient in need thereof comprising: administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0536] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for curing, inducing remission of, causing regression of, or preventing diabetes in a patient in need thereof comprising:

[0537] a) administering to the patient about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and subsequently

[0538] b) administering to the patient about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks.

[0539] Another embodiment provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for curing, inducing remission of, causing regression of, or preventing diabetes in a patient in need thereof comprising:

[0540] a) administering to the patient about once a week for a minimum of about four weeks an escalation dose of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0541] b) administering to the patient about once a week for a minimum of about four weeks about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0542] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for curing, inducing remission of, causing regression of, or preventing diabetes mellitus in a patient in need thereof, comprising:

[0543] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for curing, inducing remission of, causing regression of, or preventing diabetes mellitus in a patient in need thereof, comprising:

[0544] a) administering to the patient about once a week for a minimum of about four weeks an escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0545] b) administering to the patient about once a week for a minimum of about four weeks a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0546] c) administering to the patient about once a week for a minimum of about four weeks an escalation dose of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0547] d) administering to the patient about once a week for a minimum of about four weeks a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

[0548] In another aspect, the present application includes the use as described in the preceding paragraph, but the use does not comprise administering a 7.5 mg escalation dose.

[0549] In another aspect, the present application provides the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for curing, inducing remission of, causing regression of, or preventing diabetes mellitus in a patient in need thereof, comprising:

[0550] a) administering to the patient about once a week for a minimum of about four weeks an escalation dose of about 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and subsequently

[0551] b) administering to said patient a maintenance dose of about 5.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0552] c) administering to said patient increasing doses of about 7.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0553] d) administering to said patient a maintenance dose of about 10.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0554] e) administering to said patient increasing doses of about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once weekly for a minimum of about four weeks; and thereafter

[0555] f) administering to said patient a maintenance dose of about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for a minimum of about four weeks.

[0556] In another aspect, the present invention comprises the use as described in the preceding paragraph, but the use does not include administering 7.5 mg ascending doses. In another aspect, the present invention comprises the use as described in the preceding paragraph, but the use does not include administering 12.5 mg ascending doses. In another aspect, the present invention comprises the use as described in the preceding paragraph, but the use does not include administering 7.5 mg and 12.5 mg ascending doses.

[0557] An embodiment of the present invention for the manufacture of the above-described medicines is wherein the ascending dose for weekly administration for four weeks is about 2.5 mg and the maintenance dose for weekly administration for four weeks is about 5.0 mg. Another embodiment of the present invention is wherein the ascending dose for weekly administration for four weeks is about 7.5 mg and the maintenance dose for weekly administration for four weeks is about 10.0 mg. Another embodiment of the present invention is wherein the ascending dose for weekly administration for four weeks is about 12.5 mg and the maintenance dose for weekly administration for four weeks is about 15.0 mg. Another embodiment of the present invention is wherein the ascending dose for weekly administration for four weeks is about 2.5 mg and about 7.5 mg and the maintenance dose for weekly administration for four weeks is about 5.0 mg and about 10.0 mg. Another embodiment of the present invention is wherein the ascending dose for weekly administration for four weeks is about 2.5 mg, about 5.0 mg and about 7.5 mg and the maintenance dose for weekly administration for four weeks is about 5.0 mg, about 10.0 mg and about 15.0 mg.

[0558] In embodiment 1a, is the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the prevention of diabetes in a patient in need thereof comprising: administration of an escalation dose once about weekly for a minimum of about two weeks and subsequent administration of a maintenance dose once about weekly for a minimum of about two weeks; wherein the escalation 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; wherein 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 wherein the maintenance dose following the escalation dose is an incremental increase of about 5.0 mg relative to the escalation dose.

[0559] In embodiment 2a, is the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the prevention of diabetes in a patient in need thereof comprising: administration of an escalation dose once about weekly for a minimum of about four weeks and subsequent administration of a maintenance dose once about weekly for a minimum of about four weeks; wherein the escalation 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; wherein 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 wherein the maintenance dose following the escalation dose is an incremental increase of about 5.0 mg relative to the escalation dose.

[0560] In embodiment 3a, is the use of embodiment 1a or 2a, wherein the escalation dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

[0561] In embodiment 4a, is the use of embodiment 1a or 2a, wherein the escalation dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

[0562] In embodiment 5a, is the use of embodiment 1a or 2a, wherein the escalation dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

[0563] In embodiment 6a, is the use of embodiment 3a, further comprising an escalation dose of about 7.5 mg and a maintenance dose of about 10.0 mg.

[0564] In embodiment 7a, is the use of embodiment 6a, further comprising an escalation dose of about 12.5 mg and a maintenance dose of about 15.0 mg. In embodiment 8a, is the use of tirzepatide, 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 escalation dose about once weekly for a minimum of about two weeks and thereafter administering a maintenance dose about once weekly for a minimum of about two weeks; wherein the escalation dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the escalation dose is an incremental increase of 2.5 mg relative to the escalation dose.

[0565] In embodiment 9a, is the use of tirzepatide, 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 at least one escalation dose about once weekly for a minimum of about four weeks and administering at least one maintenance dose about once weekly following the escalation dose for a minimum of about four weeks; wherein the escalation dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the escalation dose is an incremental increase of about 5.0 mg relative to the escalation dose.

[0566] In embodiment 10a, is the use of embodiment 8a or 9a, wherein the escalation dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

[0567] In embodiment 11a, is the use of embodiment 8a or 9a, wherein the escalation dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

[0568] In embodiment 12a, is the use of embodiment 8a or 9a, wherein the escalation dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

[0569] In embodiment 13a, is the use of embodiment 10a, further comprising an escalation dose of about 7.5 mg and a maintenance dose of about 10.0 mg.

[0570] In embodiment 14a, is the use of embodiment 13a, further comprising an escalation dose of about 12.5 mg and a maintenance dose of about 15.0 mg.

[0571] In another aspect, the present application provides tirzepatide, or a pharmaceutically acceptable salt thereof, for use in the treatment of type 2 diabetes. In one embodiment, the present application provides tirzepatide, or a pharmaceutically acceptable salt thereof, for use in the treatment of type 2 diabetes in a patient in need thereof, wherein: an escalation dose is administered once about weekly for a minimum of about four weeks and thereafter a maintenance dose is administered once about weekly for a minimum of about four weeks; wherein the escalation 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; wherein 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 wherein the maintenance dose following the escalation dose is an incremental increase of 2.5 mg relative to the escalation dose. In another aspect, the present application provides tirzepatide, or a pharmaceutically acceptable salt thereof, for use in improving glycemic control. In another aspect, the present application provides tirzepatride, or a pharmaceutically acceptable salt thereof, for use in improving glycemic control in a patient in need thereof, wherein: an escalation dose is administered once about weekly for a minimum of about four weeks and thereafter a maintenance dose is administered once about weekly for a minimum of about four weeks; wherein the escalation 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; wherein 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 wherein the maintenance dose following the escalation dose is an incremental increase of 2.5 mg relative to the escalation dose. In another aspect, the present application provides tirzepatide, or a pharmaceutically acceptable salt thereof, for use in improving weight management. In another aspect, the present application provides tirzepatride, or a pharmaceutically acceptable salt thereof, for use in improving weight management in a patient in need thereof, wherein: an escalation dose is administered once about weekly for a minimum of about four weeks and thereafter a maintenance dose is administered once about weekly for a minimum of about four weeks; wherein the escalation 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; wherein 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 wherein the maintenance dose following the escalation dose is an incremental increase of 2.5 mg relative to the escalation dose. In another aspect, the present application provides tirzepatide, or a pharmaceutically acceptable salt thereof, for use in the treatment of chronic kidney disease.In another aspect, the present application provides tirzepatide, or a pharmaceutically acceptable salt thereof, for use in treating chronic kidney disease in a patient in need thereof, wherein: an escalation dose is administered about once weekly for a minimum of about four weeks and thereafter a maintenance dose is administered about once weekly for a minimum of about four weeks; wherein the escalation 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; wherein 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 wherein the maintenance dose following the escalation dose is an incremental increase of 2.5 mg relative to the escalation dose. In another aspect, the present application provides tirzepatide, or a pharmaceutically acceptable salt thereof, for use in treating atherosclerosis. In another aspect, the present application provides tirzepatide, or a pharmaceutically acceptable salt thereof, for use in treating atherosclerosis in a patient in need thereof, wherein: an escalation dose is administered about once weekly for a minimum of about four weeks and thereafter a maintenance dose is administered about once weekly for a minimum of about four weeks; wherein the escalation 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; wherein 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 wherein the maintenance dose following the escalation dose is an incremental increase of 2.5 mg relative to the escalation dose. In another aspect, the present application provides tirzepatide, or a pharmaceutically acceptable salt thereof, for use in treating NAFLD. In another aspect, the present application provides tirzepatide, or a pharmaceutically acceptable salt thereof, for use in treating NAFLD in a patient in need thereof, wherein: an escalation dose is administered about once weekly for a minimum of about four weeks and thereafter a maintenance dose is administered about once weekly for a minimum of about four weeks; wherein the escalation 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; wherein 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 wherein the maintenance dose following the escalation dose is an incremental increase of 2.5 mg relative to the escalation dose. In another aspect, the present application provides tirzepatide, or a pharmaceutically acceptable salt thereof, for use in treating NASH.In another aspect, the present application provides tirzepatide, or a pharmaceutically acceptable salt thereof, for use in treating NASH in a patient in need thereof, wherein: an escalation dose is administered once about weekly for a minimum of about four weeks and thereafter a maintenance dose is administered once about weekly for a minimum of about four weeks; wherein the escalation 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; wherein 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 wherein the maintenance dose following the escalation dose is an incremental increase of 2.5 mg relative to the escalation dose. In another aspect, the present application provides tirzepatide, or a pharmaceutically acceptable salt thereof, for use in curing, causing remission or regression of, or preventing diabetes. In another aspect, the present application provides tirzepatide, or a pharmaceutically acceptable salt thereof, for use in curing, causing remission or regression of, or preventing diabetes in a patient in need thereof, wherein: an escalation dose is administered once about weekly for a minimum of about four weeks and thereafter a maintenance dose is administered once about weekly for a minimum of about four weeks; wherein the escalation 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; wherein 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 wherein the maintenance dose following the escalation dose is an incremental increase of 2.5 mg relative to the escalation dose.

[0572] One embodiment of the present application for the above uses is where the escalation dose administered once weekly for four weeks is about 2.5 mg and the maintenance dose administered once weekly for four weeks is about 5.0 mg. Another embodiment of the present application is where the escalation dose administered once weekly for four weeks is about 7.5 mg and the maintenance dose administered once weekly for four weeks is about 10.0 mg. Another embodiment of the present application is where the escalation dose administered once weekly for four weeks is about 12.5 mg and the maintenance dose administered once weekly for four weeks is about 15.0 mg. Another embodiment of the present application is where the escalation dose administered once weekly for four weeks is about 2.5 mg and about 7.5 mg and the maintenance dose administered once weekly for four weeks is about 5.0 mg and about 10.0 mg. Another embodiment of the present application is where the escalation dose administered once weekly for four weeks is about 2.5 mg, about 5.0 mg, and about 7.5 mg and the maintenance dose administered once weekly for four weeks is about 5.0 mg, about 10.0 mg, and about 15.0 mg.

[0573] As used herein, "titration dose" or "escalating dose" means a dose that is less than the highest effective dose required by the patient. As used herein, the present application contemplates that a "titration dose" or "escalating dose" can become the highest effective dose required by the patient, or if it is observed that this dose is the effective dose required by the patient, it can become a "maintenance dose," and this dose can be administered chronically for a period of time that exceeds four weeks.

[0574] As used herein, "maintenance dose" means a dose that is the highest effective dose required by the patient, and when the maintenance dose is less than the highest effective dose required, this maintenance dose can become an escalating dose. That is, if for a particular patient, the "about 5 mg" maintenance dose contemplated by the present application is not the highest effective dose required, then the 5 mg maintenance dose will in turn become a titration dose, because the dose for that particular patient will be escalated until the next highest maintenance dose contemplated by the present application is achieved, e.g., 7.5 mg for at least about 2 weeks to 10 mg for at least about 2 weeks. The present application contemplates that a patient who reaches a maintenance dose of about 10 mg or about 15 mg, as determined by the physician or other health care provider, can need to have their dose reduced to a lower maintenance dose.

[0575] Also provided herein is tirzepatide for use in simultaneous, separate, and sequential combination with one or more agents selected from metformin, thiazolidinediones, sulfonylureas, dipeptidyl peptidase 4 inhibitors, sodium glucose co-transporters, SGLT-2 inhibitors, growth differentiation factor 15 regulators ("GDF15"), peptide tyrosine tyrosine regulators ("PYY"), modified insulins, amylin, dual amylin calcitonin receptor agonists, and oxyntomodulin agonists ("OXM"). Also provided herein are compounds of the invention for use in simultaneous, separate, and sequential combination with one or more agents selected from metformin, thiazolidinediones, sulfonylureas, dipeptidyl peptidase 4 inhibitors, sodium glucose co-transporters, SGLT-2 inhibitors, GDF15, PYY, modified insulins, amylin, dual amylin calcitonin receptor agonists, and oxyntomodulin agonists ("OXM"). Also provided herein are compounds of the invention for use in simultaneous, separate, and sequential combination with one or more agents selected from metformin, thiazolidinediones, sulfonylureas, dipeptidyl peptidase 4 inhibitors, sodium glucose co-transporters, SGLT-2 inhibitors, GDF15, PYY, modified insulins, amylin, dual amylin calcitonin receptor agonists, and OXM for improving glycemic control and / or weight management. Also provided herein are compounds of the invention for use in simultaneous, separate, and sequential combination with one or more agents selected from metformin, thiazolidinediones, sulfonylureas, dipeptidyl peptidase 4 inhibitors, sodium glucose co-transporters, SGLT-2 inhibitors, GDF15, PYY, modified insulin, amylin, dual amylin calcitonin receptor agonists, and OXM for curing diabetes, causing remission or regression of diabetes, or preventing diabetes. In one embodiment, the compounds of the invention are provided in a fixed dose combination with one or more agents selected from metformin, thiazolidinediones, sulfonylureas, dipeptidyl peptidase 4 inhibitors, sodium glucose co-transporters, SGLT-2 inhibitors, GDF15, PYY, modified insulin, amylin, dual amylin calcitonin receptor agonists, and OXM.

[0576] NAFLD and NASH treatment

[0577] Nonalcoholic fatty liver disease (“NAFLD”) is a liver disease characterized by the accumulation of fat in the liver of affected patients. Patients with NAFLD may consume little or no alcohol and, in one embodiment, do not have comorbid diabetes. NAFLD is the leading cause of liver disease worldwide. Younossi et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes; Hepatology (July 2016) 64:1;73-84. Nonalcoholic steatohepatitis (“NASH”) is a type of NAFLD with an etiological combination showing macrovesicular hepatic steatosis, inflammation, hepatocellular ballooning, and fibrosis. NASH can lead to cirrhosis and liver failure. It has been determined that patients with NASH are more likely to develop cirrhosis and have a higher risk of cardiovascular death and hepatocellular carcinoma. This nonalcoholic, nonviral form of cirrhosis is actually among the leading reasons for liver transplantation.

[0578] NAFLD and NASH are chronic progressive diseases characterized by the formation of liver fibrosis as NAFLD progresses to NASH. NASH staging can be defined, for example, according to the NASH CRN (Clinical Research Network). Fibrosis staging measures the amount and pattern of NASH fibrosis and parenchymal structural remodeling in patients. NASH is generally diagnosed using a liver biopsy in human patients, and is predicted using MRI-derived proton density fat ratio maps ("MRI-PDFF"), plasma cytokeratin 18 (CK18) fragment levels as a biomarker for hepatocyte apoptosis, and plasma Pro-C3 (N-terminal type III collagen propeptide) and / or other biomarkers to predict fibrosis progression. Vincent Wai-Sun Wong et al. Noninvasive biomarkers in NAFLD and NASH - current progress and future promise; Nature Reviews Gastroenterology & Hepatology; (May 29, 2018). Imaging methods such as MRI-PDFF are generally used to assess NAFLD, where excessive lipid deposition occurs in the liver.

[0579] Currently, there are no approved drugs specifically for the treatment of NASH. Current recommendations for NASH patients include diet and exercise. There is a need for additional treatment options for patients with NAFLD and NASH.

[0580] The present application provides a method of treating NAFLD comprising administering to a patient in need of such treatment an effective amount of tirzepatide, or a pharmaceutically acceptable salt thereof. The present application provides a method of treating NASH comprising administering to a patient in need of such treatment an effective amount of tirzepatide, or a pharmaceutically acceptable salt thereof. In one embodiment, the patient in need of treatment for NASH has co-morbid type 2 diabetes. In one embodiment, the patient in need of treatment for NASH does not have co-morbid type 2 diabetes.

[0581] Chronic kidney disease treatment

[0582] Chronic kidney disease ("CKD") is defined as an abnormality in kidney structure or function that involves the health of a patient for three months. CKD can be classified into five categories based on glomerular filtration rate ("GFR"). GFR can be estimated using biomarkers, including serum creatinine and albumin, urine albumin-to-creatinine ratio ("ACR"), and serum cystatin C. Moderate CKD (GFR 30-59 mL / min / 1.73 m 2 ) is classified as stage 3 CKD. In the adult population, a decrease in GFR is associated with an increase in risk of cardiovascular disease ("CVD") independent of other cardiovascular ("CV") risk factors. CV mortality is two-fold and three-fold higher in patients with stage 3 and stage 4 CKD, respectively, when compared to patients with normal kidney function. Patients with CKD and established CVD have a much higher mortality rate than patients with CVD and normal kidney function. Thus, CKD patients are identified as being at high risk (stage 3 CKD) or very high risk (stage 4-5 CKD or dependent on dialysis). Treatment of CKD patients generally includes diet, exercise, smoking cessation, antihypertensive medications, and a combination of multiple medical interventions. Needed CKD treatments reduce inflammation, improve glycemic control, and / or improve cellular function in such patients. Additional treatment options are needed for CKD patients.

[0583] The present application provides a method of treating CKD comprising administering to a patient in need thereof an effective amount of tirzepatide. In one embodiment, the treatment is for a patient with stage 3 CKD. In one embodiment, the treatment is for a patient with stage 4 CKD. In one embodiment, the treatment is for a patient with stage 2 CKD. In one embodiment, the treatment is for a patient with stage 1 CKD.

[0584] Atherosclerosis treatment

[0585] Atherosclerosis is a condition that develops when plaques build up in the walls of arteries. This buildup narrows the arteries, hindering the flow of blood. Complications associated with atherosclerosis and progression of atherosclerotic conditions can lead to heart attack or stroke. Despite recent advances in treatment options, cardiovascular disease remains a leading cause of death in the diabetic population. The present invention provides a method of treating atherosclerosis comprising administering to a patient in need thereof an effective amount of tirzepatide.

[0586] Curing diabetes, causing remission or regression of diabetes, or preventing diabetes

[0587] US 9,474,780 teaches that tirzepatide can be used to treat diabetes, where "treat" includes preventing, slowing, stopping, or reversing the progression or severity of an existing symptom or condition. Despite advances in diabetes treatment, many patients receiving such treatment are unable to achieve their glycemic control goals or HbAlc goals.

[0588] US 9,474,780 teaches that tirzepatide is useful for treating diabetes, where "treating" includes preventing, slowing, stopping, or reversing the progression or severity of an existing symptom or condition. Despite advances in diabetes treatment, many patients receiving such treatment are unable to achieve their glycemic control or HbAlc goals. The present invention provides a method of curing diabetes, where a patient receiving treatment for diabetes is administered a tirzepatide dosing regimen comprising a starting dose or escalation dose of 2.5 mg tirzepatide once weekly for four weeks, and a maintenance dose of 5.0 mg tirzepatide once weekly for at least four weeks; if the patient does not achieve their HbAlc goal, an escalation dose of about 7.5 mg once weekly for at least four weeks and a subsequent maintenance dose of 10.0 mg tirzepatide once weekly for at least four weeks is administered; where if the patient does not achieve their HbAlc goal from treatment using a 10.0 mg once weekly dose for at least 4 weeks, an escalation dose of 12.5 mg tirzepatide once weekly for at least 4 weeks, followed by a maintenance dose of 15 mg once weekly until the HbAlc goal is achieved for at least about 2 weeks can be administered, and where the patient maintains their HbAlc goal after discontinuing all medications approved for the treatment of diabetes or glycemic control. As used herein, the terms "medication for diabetes," "diabetes medication," and the like refer to a medication approved by a relevant regulatory agency for the treatment of type 2 diabetes or glycemic control. In one embodiment, the patient treated for diabetes has an HbAlc value of less than or equal to about 5.9%. In one embodiment, the patient maintains their HbAlc goal level for at least one month without further administration of tirzepatide. In one embodiment, a patient previously treated for diabetes with tirzepatide maintains their glycemic goal for at least one month without further administration of tirzepatide or any other diabetes medication. In one embodiment, the patient maintains their glycemic goal for at least 6 months without further administration of tirzepatide or any other diabetes medication.

[0589] As used herein, the terms "diabetes medication," "diabetes drug," and the like refer to a drug approved by a relevant regulatory agency for the treatment of type 2 diabetes or glycemic control. In one embodiment, the patient being treated for diabetes has an HbAlc value of less than or equal to about 5.9%. In one embodiment, the patient maintains their HbAlc target level for at least one month without further administration of tirzepatide. In one embodiment, the patient previously treated for diabetes with tirzepatide maintains their glycemic target for at least one month without further administration of tirzepatide or any other diabetes drug. In one embodiment, the patient maintains their glycemic target for at least 6 months without further administration of tirzepatide or any other diabetes drug.

[0590] Doses of the present application can 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 can be provided in pre-filled syringes. Such pre-filled syringes can be used to administer one and a half milliliters of such composition per dose per patient. Doses of the present application are generally administered subcutaneously. These doses are generally administered using a pre-filled disposable injection pen, a reusable pen, or an auto-injector. In one embodiment, the device is an auto-injection device as claimed in U.S. Patent 8,734,394.

[0591] As used herein, "tirzepatide" refers to the GIP / GLP1 dual agonist peptide as described in US 9,474,780 and as described in accordance with CAS Registry Number: 2023788-19-2.

[0592] Example 1 of US 9,474,780 describes Tirzepatide, the sequence of which is as follows:

[0593] YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS

[0594] wherein X1is Aib; X2is Aib; K at position 20 is chemically modified by conjugation of the epsilon-amino group of the K side chain with (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(yGlu)i-CO-(CH2) 18 -CO2H; and the C-terminal amino acid is amidated as a C-terminal primary amide (SEQ ID NO: 1).

[0595] As used herein, the term "administering" means administration by a nurse, health care provider, patient, or any other individual, including self-administration. This includes not only delivery into the body, but also prescribing, dispensing, or otherwise assisting in the delivery in any way.

[0596] As used herein, the terms "increasing dose," "increasing maintenance dose," "increasing titration dose," and "increasing escalation dose" mean raising the respective dose by a nurse, health care provider, patient, or any other individual.

[0597] As used herein, "pharmaceutically acceptable salts" are well known to the skilled artisan. In one embodiment the pharmaceutically acceptable salt is tirzepatide trifluoroacetate. In one embodiment tirzepatide is in a non-salt form.

[0598] As used herein, the term "biomarker" refers to a laboratory measure that reflects the activity of the disease process. Biomarkers can be used to diagnose a disease or condition, and are often quantitatively related to disease progression (either positively or negatively). In the context of a clinical trial, biomarkers are indicators of the likely, but not necessarily precise, relationship of the effects of a particular treatment to actual clinical endpoints; that is, biomarkers are surrogate indicators of clinical endpoints.

[0599] As used herein, the terms "treat," "treatment," and the like, are intended to include delaying or lessening the progression of a disease or condition. These terms include alleviating, relieving, or reducing one or more symptoms of a condition or disease, even if the condition or disease is not eliminated or the progression is not slowed.

[0600] As used herein, "curing diabetes" means that a patient with diabetes achieves their glycemic control treatment goal using tirzepatide treatment. The tirzepatide treatment that cures diabetes can prevent diabetes, reduce its severity, or cause its remission in such a patient. In one embodiment, the tirzepatide treatment slows the progression of diabetes in a patient in need of such treatment. In one embodiment, a patient with diabetes achieves their glycemic control treatment goal using tirzepatide treatment 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 achieves at least their glycemic control treatment goal and the treatment goal is maintained when treatment with tirzepatide and all other diabetes medications is stopped. In one embodiment, a patient using tirzepatide for the treatment of diabetes achieves at least their glycemic control treatment goal and the treatment goal is maintained for at least about one month when treatment with tirzepatide and all other diabetes medications is stopped. In one embodiment, a patient using tirzepatide for the treatment of diabetes achieves at least their glycemic control treatment goal and the treatment goal is maintained for at least about six months when treatment with tirzepatide and all other diabetes medications is stopped. In one embodiment, the patient was unable to achieve their glycemic goal prior to tirzepatide treatment. In one embodiment, the patient did not achieve their glycemic goal using oral diabetes medications. In one embodiment, the patient did not achieve their glycemic goal using metformin treatment. In one embodiment, the patient's glycemic goal is less than about 5.9% HbAlc.

[0601] As used herein, "glycemic control" means maintaining or lowering a patient's HbAlc level; "improving" glycemic control means lowering HbAlc.

[0602] As used herein, "weight management" means managing obesity in an individual; "improving" weight management means lowering body weight.

[0603] As used herein, "HbAlc" means the level of glycosylated hemoglobin, which forms when hemoglobin becomes joined with glucose in the blood. HbAlc levels are a commonly used indicator of glycemic control in patients with diabetes, and a lower HbAlc level generally indicates improved glycemic control. In the context of the methods of the application, the methods of the application result in a lowering of HbAlc. In certain embodiments, the lowering of HbAlc refers to a lowering of the HbAlc level relative to that which would result from treatment with a lower dose of tirzepatide.

[0604] As used herein, "patient" 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 tirzepatide.

[0605] The term "LOCF" or last observation carried forward is a statistical analysis method recognized by skilled statisticians as a means to impute missing data. The term "ITT" or intent to treat is a statistical analysis method recognized by skilled statisticians as an intent to treat analysis method in which participants are analyzed according to the group to which they were initially assigned.

[0606] Preparation #1 - Tirzepatide compositions containing NaCl

[0607] The compositions were prepared essentially as described herein. The compositions containing 5, 10, 15, 20, 15, and 30 mg / mL of tirzepatide each contained the ingredients described in Table 1. Acid or base was optionally added to achieve the desired pH range. Water was added q.s. to a total final volume of 1 milliliter.

[0608] Table 1. Formulation of tirzepatide, phosphate, and NaCl

[0609] Ingredients Concentration (mg / mL) Tirzepatide 5, 10, 15, 20, 25, and 30 Sodium phosphate dibasic 1.34 NaCI 8.2

[0610] *Using 5 mM phosphate buffer

[0611] Preparation #2 - Tirzepatide compositions containing propylene glycol

[0612] The compositions were prepared essentially as described herein. The compositions containing 5, 10, 15, 20, 15, and 30 mg / mL of tirzepatide each contained the ingredients described in Table 2. Acid or base was optionally added to achieve the desired pH range. Water was added q.s. to a total final volume of 1 milliliter.

[0613] Table 2. Formulation of tirzepatide, phosphate, and propylene glycol

[0614] Ingredients Concentration (mg / mL) Tirzepatide 5, 10, 15, 20, 25, and 30 Sodium phosphate dibasic 1.34 Propylene glycol 15

[0615] *Using 5 mM phosphate buffer

[0616] Clinical study supporting maintenance dose implementation (NCT03131687)

[0617] A 6-month (26-week) Phase II double-blind clinical study was designed to evaluate the safety, efficacy, and PK / PD of subcutaneous once-weekly (QW) tirzepatide at 4 dose levels (1 mg, 5 mg, 10 mg, and 15 mg, respectively) compared with QW dulaglutide 1.5 mg and placebo in patients with inadequate glycemic control on diet and exercise with or without stable dose metformin in patients with T2DM. The tirzepatide dose was titrated upward to the maintenance dose using the following weekly dose increments:

[0618]

[0619] The study also had a 4-week follow-up phase. In addition to the safety and efficacy of treating T2DM, the efficacy endpoints included the effect of tirzepatide on HbAlc, FBG, body weight, lipids, and waist circumference compared with placebo and compared with dulaglutide 1.5 mg. The study also evaluated the effect of tirzepatide on GI tolerability, hypoglycemia, hypersensitivity, and pancreatic safety and the formation of anti-drug antibodies that occurred during treatment. Model-based dose response analyses were conducted to predict the likelihood of significant HbAlc reduction and weight loss in longer-term studies.

[0620] Statistical Analysis

[0621] Potency The primary efficacy outcome of change in HbAlc from baseline to the 26-week endpoint was analyzed using a Bayesian dose-response model. The analysis was conducted on the intent-to-treat population (mITT) analysis set. Supportive analyses of the primary efficacy outcome for the mITT dataset were based on body mass index (BMI) (<30 kg / m 2 , >30 kg / m 2 ), metformin use, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline HbAlc as a covariate, and patient as a random effect (MMRM) model.

[0622] As a primary analysis, similar dose-effect models were used to analyze the mean change from baseline in body weight at 12 and 26 weeks and the mean change from baseline in HbAlc at 12 weeks. The percentage of patients with >5% or >10% weight loss, who achieved HbAlc target of <6.5% or <7.0% at 26 weeks, or who required rescue therapy were analyzed using logistic regression with treatment and stratification as fixed effects and baseline as a covariate. The mean percent change from baseline in FBG (fasting blood glucose), SMBG (self-monitored blood glucose) levels, waist circumference, and lipids at 12 and 26 weeks were analyzed using a similar MMRM as used for the primary analysis.

[0623] Table Abbreviations: Dula 1.5 mg = dulaglutide 1.5 mg once weekly; LY refers to tirzepatide and LY 1 mg = tirzepatide 1 mg once weekly; LY 5 mg = 5 mg once weekly; LY 10 mg = escalating dose tirzepatide once weekly, maximum dose 10 mg; LY 15 mg = escalating dose tirzepatide once weekly, maximum dose 15 mg; LOCF = last observation carried forward; N = number of patients; pbo = placebo; Week 26 = mITT on-treatment data at Week 26, excluding data after study drug discontinuation or rescue medication initiation; mITT = modified intent-to-treat; SD = standard deviation. For Table 4, n = number of patients in the population with both baseline and post-baseline values at the specified time point. For Table 6, LY 10 mg = escalating dose tirzepatide once weekly, maximum dose 10 mg; Escalating Dose: (5 mg Weeks 0 and 1); LY 15 mg = escalating dose tirzepatide once weekly, maximum dose 15 mg; Escalating Dose: (5 mg Weeks 0 and 1; 10 mg Weeks 2-5); N = number of patients in the specified group, m = number of patients with a new event occurring during the interval, FolUp = follow-up, T / Wk = time range (weeks), and % = percentage of patients in the treatment group experiencing at least some time during the interval with a new event. For Table 7, n is the number of patients with an event that met criteria; N is the number of patients in the population; % is the percentage of patients in the treatment group with an event.

[0624] Table 3. HbAlc data

[0625]

[0626] The data in Table 3 support that the 5 mg, 10 mg, and 15 mg doses of tirzepatide significantly reduced HbAlc from baseline and were significantly different from placebo. The skilled artisan will appreciate that HbAlc values less than 5.7% are consistent with levels observed in non-diabetic patients. The tirzepatide dose groups were also significantly different from dulaglutide 1.5 mg.

[0627] The percentage of patients in Table 3 who achieved the HbAlc treatment goal indicates that more patients receiving study drug in the tirzepatide 15 mg group achieved the treatment goal of HbAlc < 5.7% than in any other treatment group.

[0628] Table 4. Mean fasting glucose values

[0629]

[0630] As expected from the observed changes in HbAlc, as shown in Table 4, the 5 mg, 10 mg, and 15 mg doses of tirzepatide significantly reduced fasting glucose compared to placebo and dulaglutide 1.5 mg.

[0631] Table 5. Weight loss

[0632]

[0633] Table 5 summarizes the proportion of patients achieving >5%, >10%, and >15% weight loss goals at Week 26. The 5 mg, 10 mg, and 15 mg doses of tirzepatide significantly reduced weight from baseline and were significantly different from placebo. The tirzepatide 5 mg, 10 mg, and 15 mg groups were also significantly different from dulaglutide 1.5 mg.

[0634] As shown in Table 5 summarizing the clinical study, a higher percentage of patients in the tirzepatide 15 mg group were able to achieve greater than 15% mean weight loss.

[0635] Table 6. Nausea, Vomiting, and Diarrhea

[0636]

[0637] Table 6 illustrates the favorable impact on gastrointestinal adverse event rates using the methods herein.

[0638] Table 7. Reduced Appetite

[0639]

[0640] Appetite reduction is a centrally mediated effect. The data presented in Table 7, which is reported from a clinical trial, shows that tirzepatide has some centrally mediated effects. The centrally mediated tirzepatide activity can provide an additional therapeutic option for patients seeking treatment to provide centrally mediated GIP / GLP1 agonist activity.

[0641] In NCT03131687, the 15 mg dose was associated with more GI adverse events and a higher frequency of patients discontinuing study treatment early after a relatively short escalation. A 15 mg dose with more acceptable tolerability characteristics is needed. Data from NCT03131687 support the 15 mg dose as the highest maintenance dose in the clinic covered by the present invention. Escalation regimens as claimed herein were investigated to facilitate a 15 mg maintenance dose that can be accepted with tolerable tolerability. See the clinical study below (NCT03311724).

[0642] The clinical study (NCT03311724) supported an incremental escalation of 2.5

[0643] This was a 12-week treatment with a 1-week screening (Visit 1), followed by a 1-week run-in (Visit 2), followed by 12 weeks of treatment (Visits 3-10, including telephone visits), followed by 4 weeks of safety visits. It was a Phase II study designed to investigate the efficacy and tolerability of once-weekly subcutaneous administration of tirzepatide compared to placebo in patients with type 2 diabetes mellitus who had inadequate glycemic control with diet and exercise alone or with a stable dose of metformin. The study was designed and conducted to refine the escalation regimen according to the following.

[0644]

[0645] Table 8. HbAlc data at Week 12 - mITT population of the intent-to-treat dataset

[0646]

[0647]

[0648] LOCF = Last Observation Carried Forward; LY = tirzepatide; mITT = modified intent-to-treat; N = number of patients; pbo = placebo; Week 12: mITT intent-to-treat at Week 12, excluding data after study drug discontinuation or rescue medication initiation; LOCF Week 12: mITT intent-to-treat, excluding data after study drug discontinuation or rescue medication initiation, with last observation carried forward to Week 12.

[0649] As shown in Table 8, the placebo-adjusted change from baseline in HbAlc for 12 mg and 15 mg tirzepatide doses was statistically significant and clinically meaningful after 12 weeks of treatment, including the 8-week escalation phase.

[0650] Table 9. Body weight loss data at Week 12 - mITT population of the intent-to-treat dataset

[0651]

[0652]

[0653] LOCF = last observation carried forward; LY = tirzepatide; mITT = modified intent-to-treat; N = number of patients; pbo = placebo; Week 12: treated mITT at Week 12, excluding data after study drug discontinuation or rescue medication initiation; LOCF Week 12: treated mITT, excluding data after study drug discontinuation or rescue medication initiation, last observation carried forward to Week 12.

[0654] As shown in Table 9, both tirzepatide doses had significant weight loss compared to placebo at 12 weeks.

[0655] Table 10. Nausea, Vomiting, and Diarrhea

[0656]

[0657]

[0658] LY 12 mg Group 3 above = escalating dose group of tirzepatide once weekly, in the order 4 mg x 4, 8 mg x 4, 12 mg x 4

[0659] LY 15 mg-Group 1 above = escalating dose group of tirzepatide once weekly, in the order 2.5 mg x 2, 5 mg x 2, 10 mg x 4, 15 mg x 4

[0660] LY 15 mg-Group 2 above = escalating dose group of tirzepatide once weekly, in the order 2.5 mg x 4, 7.5 mg x 4, 15 mg x 4

[0661] M = number of patients who spent some time in the interval

[0662] m = number of patients who had a new event during the interval, where a new event means that the patient had a new onset of the event during this time period

[0663] N = number of patients in the specified treatment group

[0664] 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. No patients discontinued the study due to gastrointestinal tolerability adverse events or any other adverse events.

[0665] Based on these data from NCT03311724 above, further support is gained using an escalation regimen with 2.5 mg dose increments every 4 weeks.

[0666] Biomarkers

[0667] Clinical relevant biomarkers were measured in clinical studies to further support the use of tirzepatide for the treatment of chronic kidney disease. In study NCT03131687, no eGFR decline was observed at any dose. Clinical laboratory values support the use of tirzepatide for the treatment of chronic kidney disease. Clinical relevant biomarkers were measured to assess and support the use of tirzepatide for the treatment of atherosclerosis. Clinical relevant triglyceride levels were decreased in all tirzepatide treatment groups. Clinical observations support that tirzepatide can be beneficial for the treatment of atherosclerosis.

[0668] Biomarkers predictive of NAFLD were observed during clinical studies to demonstrate the beneficial effects of tirzepatide in the treatment of NAFLD. Biomarkers predictive of NASH were observed during clinical studies to demonstrate the beneficial effects of tirzepatide in the treatment of NAFLD. HbAlc levels were measured in tirzepatide treated patients who achieved their glycemic control goal and discontinued use of diabetes medications during follow-up to verify diabetes remission in such patients.

[0669] Example 1

[0670] Clinical dosing regimen

[0671] A clinical trial was conducted to investigate the three maintenance doses (5.0 mg, 10.0 mg, and 15.0 mg) of the present application following a dosing regimen according to the present application.

[0672] The starting dose of tirzepatide was 2.5 mg once weekly for 4 weeks, followed by an increase to 5 mg once weekly for the duration of the study in the low-dose group.

[0673] For the 10-mg group, the starting dose of tirzepatide was 2.5 mg once weekly for 4 weeks, followed by an increase in dose every 4 weeks by 2.5 mg (5 mg once weekly for 4 weeks, followed by 7.5 mg once weekly for four weeks), until the 10-mg dose was reached and maintained during the duration of the study.

[0674] For the 15-mg group, the starting dose of tirzepatide was 2.5 mg once weekly for 4 weeks, followed by increases of 2.5 mg every 4 weeks (5 mg once weekly for four weeks, followed by 7.5 mg once weekly for four weeks, followed by 10 mg once weekly for four weeks, followed by 12.5 mg once weekly for four weeks) until the 15-mg tirzepatide dose was reached and maintained during the duration of the study. For patients who could not tolerate the 15 mg dose, the maintenance dose could be lowered to 10 mg.

[0675] Sequence

[0676] SEQ ID NO: 1

[0677] Tirzepatide

[0678] YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS

[0679] wherein X1is Aib; X2is Aib; K at position 20 is chemically modified by attaching the ε-amino group of the K side chain to (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(yGlu)i-CO-(CH2) 18 -CO2H; and the C-terminal amino acid is amidated to a C-terminal primary amide.

Claims

1. A method of treating type 2 diabetes in a patient in need thereof, comprising: administering the escalating dose about once per week for a minimum of at least about two weeks followed by administering the maintenance dose about once per week for a minimum of at least about two weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 for treating type 2 diabetes in a patient in need thereof, comprising: at least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

3. The method of claim 1 or 2, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

4. The method of claim 1 or 2, wherein the escalating dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

5. The method of claim 1 or 2, wherein the escalating dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

6. Tirzepatide, or a pharmaceutically acceptable salt thereof, for use in treating type 2 diabetes mellitus in a patient in need thereof, wherein: At least one ascending dose is administered about once per week for a minimum of at least about two weeks and then at least one maintenance dose is administered about once per week for a minimum of at least about two weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

7. Tirzepatide or a pharmaceutically acceptable salt thereof for use according to claim 6, wherein: At least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

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

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

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

11. A method for inducing remission or regression of diabetes in a patient in need thereof, comprising: administering the escalating dose about once per week for a minimum of at least about two weeks followed by administering the maintenance dose about once per week for a minimum of at least about two weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof.

12. The method of claim 11 for inducing remission or regression of diabetes in a patient in need thereof, comprising: at least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

13. The method of claim 11 or 12, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

14. The method of claim 11 or 12, wherein the escalating dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

15. The method of claim 11 or 12, wherein the escalating dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

16. Tirzepatide, or a pharmaceutically acceptable salt thereof, for use in causing remission or regression of diabetes in a patient in need thereof, wherein: At least one ascending dose is administered about once per week for a minimum of at least about two weeks and then at least one maintenance dose is administered about once per week for a minimum of at least about two weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

17. Tirzepatide or a pharmaceutically acceptable salt thereof for use according to claim 16, wherein: At least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

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

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

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

21. Methods for preventing diabetes in patients in need thereof, comprising: The escalating dose is administered about once a week for a minimum of at least about two weeks and then the maintenance dose is administered about once a week for a minimum of at least about two weeks; wherein the escalating dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

22. The method of claim 21 for preventing diabetes in a patient in need thereof, comprising: at least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

23. The method of claim 20 or 21, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

24. The method of claim 20 or 21, wherein the escalating dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

25. The method of claim 20 or 21, wherein the escalating dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

26. Tirzepatide, or a pharmaceutically acceptable salt thereof, for use in preventing diabetes mellitus in a patient in need thereof, wherein: At least one ascending dose is administered about once per week for a minimum of at least about two weeks and then at least one maintenance dose is administered about once per week for a minimum of at least about two weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

27. Tirzepatide or a pharmaceutically acceptable salt thereof for use according to claim 26, wherein: At least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

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

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

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

31. Methods for improving weight management in patients in need, including: administering the escalating dose about once per week for a minimum of at least about two weeks followed by administering the maintenance dose about once per week for a minimum of at least about two weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof.

32. The method of claim 31 for improving weight management in a patient in need thereof, comprising: at least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

33. The method of claim 30 or 31, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

34. The method of claim 30 or 31, wherein the escalating dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

35. The method of claim 30 or 31, wherein the escalating dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

36. Tirzepatide, or a pharmaceutically acceptable salt thereof, for use in improving weight management in a patient in need thereof, wherein: At least one ascending dose is administered about once per week for a minimum of at least about two weeks and then at least one maintenance dose is administered about once per week for a minimum of at least about two weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

37. Tirzepatide or a pharmaceutically acceptable salt thereof for use according to claim 36, wherein: At least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

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

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

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

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

42. The method of claim 41 , comprising: The escalating dose is administered about once a week for a minimum of at least about two weeks and then the maintenance dose is administered about once a week for a minimum of at least about two weeks; wherein the escalating dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

43. The method of claim 41 for treating chronic kidney disease in a patient in need thereof, comprising: at least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

44. The method of claim 42 or 43, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

45. The method of claim 42 or 43, wherein the escalating dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

46. ​​The method of claim 42 or 43, wherein the escalating dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

47. Tirzepatide, or a pharmaceutically acceptable salt thereof, for use in treating chronic kidney disease in a patient in need thereof, wherein: At least one ascending dose is administered about once per week for a minimum of at least about two weeks and then at least one maintenance dose is administered about once per week for a minimum of at least about two weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

48. Tirzepatide or a pharmaceutically acceptable salt thereof for use according to claim 47, wherein: At least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

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

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

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

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

53. The method of claim 52, comprising: The escalating dose is administered about once a week for a minimum of at least about two weeks and then the maintenance dose is administered about once a week for a minimum of at least about two weeks; wherein the escalating dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

54. The method of claim 52 for treating atherosclerosis in a patient in need thereof, comprising: at least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

55. The method of claim 53 or 54, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

56. The method of claim 53 or 54, wherein the escalating dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

57. The method of claim 53 or 54, wherein the escalating dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

58. Tirzepatide, or a pharmaceutically acceptable salt thereof, for use in treating atherosclerosis in a patient in need thereof, wherein: At least one ascending dose is administered about once per week for a minimum of at least about two weeks and then at least one maintenance dose is administered about once per week for a minimum of at least about two weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

59. Tirzepatide or a pharmaceutically acceptable salt thereof for use according to claim 58, wherein: At least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

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

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

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

63. Methods for treating nonalcoholic fatty liver disease, comprising: An effective amount of tirzepatide or a pharmaceutically acceptable salt thereof is administered to a patient in need of such treatment.

64. The method of claim 63, comprising: The escalating dose is administered about once a week for a minimum of at least about two weeks and then the maintenance dose is administered about once a week for a minimum of at least about two weeks; wherein the escalating dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

65. The method of claim 63 for treating nonalcoholic fatty liver disease in a patient in need thereof, comprising: at least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

66. The method of claim 64 or 65, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

67. The method of claim 64 or 65, wherein the escalating dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

68. The method of claim 64 or 65, wherein the escalating dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

69. Tirzepatide, or a pharmaceutically acceptable salt thereof, for use in treating non-alcoholic fatty liver disease in a patient in need thereof, wherein at least one ascending dose is administered about once a week for a minimum of at least about two weeks and then at least one maintenance dose is administered about once a week for a minimum of at least about two weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

70. Tirzepatide or a pharmaceutically acceptable salt thereof for use according to claim 69, wherein: At least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

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

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

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

74. A method for treating nonalcoholic steatohepatitis, comprising: An effective amount of tirzepatide or a pharmaceutically acceptable salt thereof is administered to a patient in need of such treatment.

75. The method of claim 74, comprising: administering the escalating dose about once per week for a minimum of at least about two weeks followed by administering the maintenance dose about once per week for a minimum of at least about two weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof.

76. The method of treating nonalcoholic steatohepatitis in a patient in need thereof according to claim 74, comprising: at least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

77. The method of claim 75 or 76, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

78. The method of claim 75 or 76, wherein the escalating dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

79. The method of claim 75 or 76, wherein the escalating dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

80. Tirzepatide, or a pharmaceutically acceptable salt thereof, for use in treating nonalcoholic steatohepatitis in a patient in need thereof, wherein at least one ascending dose is administered about once a week for a minimum of at least about two weeks and then at least one maintenance dose is administered about once a week for a minimum of at least about two weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

81. Tirzepatide or a pharmaceutically acceptable salt thereof for use according to claim 80, wherein: At least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

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

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

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

85. A method of treating obesity in a patient in need thereof, comprising: administering the escalating dose about once per week for a minimum of at least about two weeks followed by administering the maintenance dose about once per week for a minimum of at least about two weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof.

86. The method of treating obesity in a patient in need thereof according to claim 85, comprising: at least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

87. The method of claim 85 or 86, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

88. The method of claim 85 or 86, wherein the escalating dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

89. The method of claim 85 or 86, wherein the escalating dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

90. Tirzepatide, or a pharmaceutically acceptable salt thereof, for use in treating obesity in a patient in need thereof, wherein: At least one ascending dose is administered about once per week for a minimum of at least about two weeks and then at least one maintenance dose is administered about once per week for a minimum of at least about two weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

91. Tirzepatide or a pharmaceutically acceptable salt thereof for use according to claim 90, wherein: At least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

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

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

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

95. A method for treating diabetic kidney disease in a patient in need thereof, comprising: administering the escalating dose about once per week for a minimum of at least about two weeks followed by administering the maintenance dose about once per week for a minimum of at least about two weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof.

96. The method of treating diabetic kidney disease in a patient in need thereof according to claim 95, comprising: at least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

97. The method of claim 95 or 96, wherein the escalating dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

98. The method of claim 95 or 96, wherein the escalating dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

99. The method of claim 95 or 96, wherein the escalating dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

100. Tirzepatide or a pharmaceutically acceptable salt thereof for use in treating diabetic kidney disease in a patient in need thereof, wherein: At least one ascending dose is administered about once per week for a minimum of at least about two weeks and then at least one maintenance dose is administered about once per week for a minimum of at least about two weeks; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof.

101. Tirzepatide or a pharmaceutically acceptable salt thereof for use according to claim 100, wherein: At least one ascending dose is administered about once per week for a minimum of about four weeks and at least one maintenance dose is administered about once per week for a minimum of about four weeks following the ascending dose; wherein the ascending dose is selected from about 2.5 mg, about 7.5 mg, and about 12.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; wherein the maintenance dose is selected from about 5.0 mg, about 10.0 mg, and about 15.0 mg of tirzepatide, or a pharmaceutically acceptable salt thereof; and wherein the maintenance dose following the ascending dose is in 2.5 mg increments.

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

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

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

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