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, whose application date is July 22, 2019 and whose invention name is “Method for treatment using GIP / GLP1 co-agonists”.

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

[0003] Diabetes mellitus is a chronic condition 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 a GIP / GLP1 co-agonist for parenteral administration and generally discloses a broad dosage range of up to about 30 mg per person per week. US9474780 discloses the use of GIP / GLP1 co-agonists for treating diabetes, obesity, and other conditions. US9474780 describes and claims tirzepatide.

[0005] It is well known that GLP1 treatment 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. In addition, 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. Dosage limitations associated with gastrointestinal adverse events may prevent administration of the desired effective dose, may undermine patient treatment compliance, and may 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 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.

[0020] 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 5.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

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

[0022] 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

[0023] 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.

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

[0025] 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

[0026] 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.

[0027] 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 10.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

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

[0029] 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

[0030] 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.

[0031] Another embodiment provides a method of treating type 2 diabetes in a patient in need thereof, the method 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 desired, 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 glycemic control 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.

[0051] Additionally, the present invention provides a method for improving glycemic control in a patient in need thereof, the method comprising:

[0052] 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

[0053] 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.

[0054] In another aspect, the present invention provides a method of improving glycemic control 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.

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

[0056] 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

[0057] 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.

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

[0059] 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

[0060] 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.

[0061] In another aspect, the present invention provides a method of 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.

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

[0063] 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

[0064] 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.

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

[0066] 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

[0067] 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.

[0068] In another aspect, the present invention provides a method of 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.

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

[0070] 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

[0071] 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

[0072] 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

[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 of treating type 2 diabetes in a patient in need thereof, comprising administering tirzepatide, or a pharmaceutically acceptable salt thereof, according to a tirzepatide dosing regimen comprising an initiation phase, at least one escalation phase, and a maintenance phase; wherein the initiation phase comprises administering 2.5 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week for at least about 2 to 4 weeks; wherein the escalation phase comprises administering a dose increasing by about 2.5 mg per week from the initiation phase dose or a previous escalation phase dose, each escalation phase lasting at least about 2 to 4 weeks, wherein the escalating dose is increased by 2.5 mg during each escalation phase until the maintenance phase is reached; and wherein the maintenance phase is administering a dose selected from the group consisting of about 5 mg, about 10 mg, and about 15 mg of tirzepatide, or a pharmaceutically acceptable salt thereof, about once per week.

[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 the patient about 10.0 mg once about weekly of tirzepatide, or a pharmaceutically acceptable salt thereof, for a minimum of about four weeks.

[0096] 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.

[0097] Another embodiment provides a method for improving glycemic control in a patient in need thereof, comprising:

[0098] 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

[0099] 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.

[0100] Another embodiment provides a method for improving glycemic control in a patient in need thereof, comprising:

[0101] 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

[0102] 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.

[0103] 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.

[0104] In another aspect, the present application provides a method for improving glycemic control in a patient in need thereof, comprising:

[0105] 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

[0106] 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

[0107] 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

[0108] 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.

[0109] 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.

[0110] In another aspect, the present invention provides a method of improving weight management in a patient in need thereof, the method comprising:

[0111] 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

[0112] 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

[0113] 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

[0114] 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

[0115] 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

[0116] 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.

[0117] 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.

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

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

[0138] 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

[0139] 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

[0140] 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

[0141] 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.

[0142] 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.

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

[0144] 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

[0145] 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

[0146] 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

[0147] 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

[0148] 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

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

[0150] 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.

[0151] In another embodiment, is a method of treating diabetic nephropathy in a patient in need thereof, the method comprising: administering an 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 over the escalation 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 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 thereafter

[0214] 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

[0215] 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.

[0216] 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.

[0217] 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 about four weeks, and thereafter 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 the escalation dose is a 2.5 mg incremental increase relative to the escalation 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 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

[0225] 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.

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

[0227] 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

[0228] 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.

[0229] In another aspect, the present application provides a method of 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.

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

[0231] 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

[0232] 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.

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

[0234] 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

[0235] 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.

[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 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

[0254] 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.

[0255] 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, 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.

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

[0257] 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

[0258] 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.

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

[0260] 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

[0261] 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.

[0262] 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, 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.

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

[0286] 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

[0287] 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.

[0288] 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 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.

[0289] 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:

[0290] 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

[0291] 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.

[0292] 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:

[0293] 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

[0294] 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.

[0295] 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 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.

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

[0309] 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:

[0310] 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

[0311] 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

[0312] 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

[0313] 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

[0314] 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

[0315] 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.

[0316] 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.

[0317] Additionally, 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 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.

[0318] In addition, 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:

[0319] 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

[0320] 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.

[0321] 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 5.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

[0322] 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:

[0323] a) administering to said patient increasing doses 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

[0324] 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.

[0325] 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:

[0326] 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

[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 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

[0339] 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

[0340] 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.

[0341] 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.

[0342] 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:

[0343] 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

[0344] 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

[0345] 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

[0346] 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

[0347] 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

[0348] 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.

[0349] 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.

[0350] Also provided is 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.

[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 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

[0372] 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

[0373] 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.

[0374] 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.

[0375] In another aspect, the present invention provides use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for improving weight management in a patient in need thereof, comprising:

[0376] 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

[0377] 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

[0378] 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

[0379] 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

[0380] 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

[0381] 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.

[0382] 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.

[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 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.

[0394] 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 10.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

[0395] 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:

[0396] 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

[0397] 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.

[0398] 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:

[0399] 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

[0400] 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.

[0401] 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 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

[0402] In another aspect, 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:

[0403] 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

[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 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

[0424] 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.

[0425] 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:

[0426] 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

[0427] 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.

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

[0429] 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:

[0430] 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

[0431] 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.

[0432] 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:

[0433] 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

[0434] 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.

[0435] In another aspect, the present invention provides 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 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

[0436] In another aspect, the present invention provides 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:

[0437] 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

[0438] 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

[0439] 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

[0440] 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.

[0441] 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.

[0442] In another aspect, the present invention provides 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:

[0443] 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

[0444] 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

[0445] 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

[0446] 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

[0447] 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

[0448] 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.

[0449] 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.

[0450] In one embodiment is a method of treating dyslipidemia in a patient in need thereof, comprising: administering an ascending dose about once a week for a minimum of at least about two weeks followed by administering a maintenance dose 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.

[0451] In one embodiment is a method for treating dyslipidemia 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.

[0452] In one embodiment is a method of treating dyslipidemia wherein the escalating 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 escalating 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 escalating dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

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

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

[0457] In one embodiment is a method of treating dyslipidemia wherein the patient in need of such treatment does not have comorbid type 1 or type 2 diabetes.

[0458] Additionally, the present invention provides a use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for treating NALFD 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.

[0459] 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:

[0460] 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

[0461] 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.

[0462] In another aspect, the present invention provides 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 5.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

[0463] Another embodiment provides the 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:

[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 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.

[0466] Another embodiment provides the 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:

[0467] 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

[0468] 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.

[0469] 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 10.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

[0470] Another embodiment provides the 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:

[0471] 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

[0472] 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.

[0473] Another embodiment provides the 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:

[0474] 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

[0475] 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.

[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 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

[0498] 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.

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

[0500] 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

[0501] 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.

[0502] In another aspect, the present invention provides use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating NASH in a patient in need thereof, comprising administering to the patient a maintenance dose of about 10.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

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

[0504] 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

[0505] 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.

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

[0507] 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

[0508] 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.

[0509] In another aspect, the present invention provides use of tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for 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.

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

[0511] 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

[0512] 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

[0513] 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

[0514] 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.

[0515] 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.

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

[0517] 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

[0518] 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

[0519] 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

[0520] 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

[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 preparation of a medicament for curing diabetes, causing remission or regression of diabetes, or preventing diabetes in a patient in need thereof, comprising:

[0530] 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

[0531] 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.

[0532] Another embodiment 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:

[0533] 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

[0534] 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.

[0535] 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 10.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

[0536] Another embodiment 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:

[0537] 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

[0538] 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.

[0539] Another embodiment 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:

[0540] 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

[0541] 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.

[0542] 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 15.0 mg of tirzepatide or a pharmaceutically acceptable salt thereof about once a week for a minimum of about four weeks.

[0543] 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:

[0544] 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

[0545] 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

[0546] 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

[0547] 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.

[0548] 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.

[0549] 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:

[0550] 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

[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 preparation of a medicament for preventing diabetes in a patient in need thereof, comprising: administering an ascending dose about once a week for a minimum of about two weeks followed by administering a maintenance dose about once a week for a minimum of 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; 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.

[0559] In embodiment 2a is the use of tirzepatide, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for 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 about 5.0 mg relative to the ascending dose.

[0560] In embodiment 3a is the use of embodiment 1a or 2a, wherein the ascending 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 ascending 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 ascending dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

[0563] In embodiment 6a, the use of embodiment 3a further comprising an ascending 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 invention provides tirzepatride, or a pharmaceutically acceptable salt thereof, for use in treating chronic kidney disease in a patient in need thereof, wherein: an ascending dose is administered about once per week for a minimum of about four weeks and a maintenance dose is subsequently administered 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. In another aspect, the present invention provides tirzepatide, or a pharmaceutically acceptable salt thereof, for use in treating atherosclerosis. In another aspect, the present invention provides tirzepatride, or a pharmaceutically acceptable salt thereof, for use in treating atherosclerosis in a patient in need thereof, wherein: an ascending dose is administered approximately once weekly for a minimum of about four weeks and a maintenance dose is subsequently administered approximately once weekly 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. In another aspect, the present invention provides tirzepatide, or a pharmaceutically acceptable salt thereof, for use in treating NAFLD. In another aspect, the present invention provides tirzepatride, or a pharmaceutically acceptable salt thereof, for use in treating NAFLD in a patient in need thereof, wherein: an ascending dose is administered approximately once weekly for a minimum of about four weeks and a maintenance dose is subsequently administered approximately once weekly 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. In another aspect, the present invention 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, a "titration dose" or "escalating dose" refers to a dose that is less than the maximum effective dose required for a patient. As used herein, the present invention contemplates that a "titration dose" or "escalating dose" can be changed to the maximum effective dose required, or if it is observed that this dose is the effective dose required for the patient, it can be changed to a "maintenance dose," and that this dose can be administered chronically for a period of more than four weeks.

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

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

[0581] Chronic kidney disease treatment

[0582] Chronic kidney disease ("CKD") is defined as abnormalities in kidney structure or function that affect the patient's health for more than three months. CKD can be divided 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, reduced GFR is associated with an increased risk of cardiovascular disease ("CVD"), regardless of other cardiovascular ("CV") risk factors. When compared with patients with normal renal function, the CV mortality rate in patients with stage 3 and stage 4 CKD is two times and three times higher, respectively. Patients with CKD and established CVD have a much higher mortality rate than patients with CVD and normal renal function. Therefore, patients with CKD are considered to be at high risk (stage 3 CKD) or very high risk (stage 4-5 CKD or dialysis dependence). Treatment of patients with CKD generally includes diet, exercise, smoking cessation, antihypertensive drugs and a combination of medical measures. The required CKD treatment reduces inflammation, improves blood sugar control and / or improves cell function in such patients. CKD patients need additional treatment options.

[0583] The present invention provides a method of treating CKD, comprising administering an effective amount of tirzepatide to a patient in need thereof. In one embodiment, the treatment is for patients with stage 3 CKD. In one embodiment, the treatment is for patients with stage 4 CKD. In one embodiment, the treatment is for patients with stage 2 CKD. In one embodiment, the treatment is for patients 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 can be used to treat diabetes, where "treating" includes preventing, delaying, stopping or reversing the progression or severity of existing symptoms or conditions. Despite advances in diabetes treatment, many patients receiving such treatments are unable to achieve their glycemic control goals or HbA1c targets. The present invention provides a method of curing diabetes, wherein a patient receiving treatment for diabetes is dosed with tirzepatide using a dosing regimen comprising a starting dose or escalating doses 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 HbA1c target, an escalating dose of about 7.5 mg once weekly is administered for at least four weeks and then a maintenance dose of 10.0 mg tirzepatide once weekly is administered for at least four weeks; wherein, if the patient does not achieve their HbA1c target from treatment with the 10.0 mg once weekly dose for at least four weeks, an escalating dose of 12.5 mg tirzepatide once weekly may be administered for at least four weeks, followed by a maintenance dose of 15 mg once weekly until the HbA1C target is achieved for at least about two weeks, and wherein the patient maintains their HbA1c target after discontinuing all medications approved for the treatment of diabetes or glycemic control. As used herein, the terms "diabetes medication," "diabetes drug," and the like refer to medications approved by relevant regulatory agencies for the treatment of type 2 diabetes or glycemic control. In one embodiment, the HbA1c level in a patient being treated for diabetes is less than or equal to about 5.9%. In one embodiment, the patient maintains their target HbA1c 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 target for at least one month without further administration of tirzepatide or any other diabetes medication. In one embodiment, the patient maintains their glycemic target for at least six 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" refers to administration by a nurse, healthcare provider, patient, or any other individual, including self-administration. This includes not only delivery into the body, but also prescribing, dispensing, or assisting in delivery in any way.

[0596] As used herein, the terms "increase the dose," "increase the maintenance dose," "increase the titrated dose," and "increase the escalating dose" refer to an increase in the 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 measurement that reflects the activity of a disease process. Biomarkers can be used to diagnose a disease or condition and are generally quantitatively correlated (positively or negatively) with disease progression. In a clinical trial setting, a biomarker is an indicator of the effect of a particular treatment that may be correlated with the actual clinical endpoint, but does not necessarily have a precise correlation; that is, a biomarker is a surrogate indicator of the clinical endpoint.

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

[0600] As used herein, "curing diabetes" means that a patient treated with tirzepatide for diabetes achieves their glycemic control treatment goal. Treatment with tirzepatide that cures diabetes can prevent diabetes, reduce its severity, or induce remission in such a patient. In one embodiment, treatment with tirzepatide slows the progression of diabetes in a patient in need of such treatment. In one embodiment, a patient treated with tirzepatide for diabetes achieves their glycemic control treatment goal and does not require concomitant diabetes medications to maintain their glycemic control goal. In one embodiment, a patient treated with tirzepatide for diabetes achieves at least their glycemic control treatment goal, and the treatment goal is maintained upon discontinuation of tirzepatide and all other diabetes medications. In one embodiment, a patient treated with tirzepatide for diabetes achieves at least their glycemic control treatment goal, and the treatment goal is maintained upon discontinuation of tirzepatide and all other diabetes medications for at least about one month. In one embodiment, a patient treated with tirzepatide for diabetes achieves at least their glycemic control treatment goal, and the treatment goal is maintained upon discontinuation of tirzepatide and all other diabetes medications for at least about six months. In one embodiment, the patient was unable to achieve their glycemic goal prior to tirzepatide treatment. In one embodiment, the patient was not achieving their glycemic goal using an oral diabetes medication. In one embodiment, the patient was not achieving their glycemic goal using metformin treatment. In one embodiment, the patient's glycemic goal was less than about 5.9% HbA1c.

[0601] As used herein, "glycemic control" refers to maintaining or lowering a patient's HbA1c level; and "improving" glycemic control means a reduction in HbA1c.

[0602] As used herein, "weight management" refers to managing obesity in an individual; "improving" weight management refers to weight loss.

[0603] As used herein, "HbA1c" refers to the level of glycated hemoglobin, which is formed when hemoglobin binds to glucose in the blood. HbA1c levels are a common indicator of glycemic control in diabetic patients, and reduced HbA1c levels generally indicate improved glycemic control. In the context of the methods of the present invention, the methods of the present invention result in a decrease in HbA1c. In certain embodiments, a decrease in HbA1c refers to a decrease in HbA1c levels relative to that resulting 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, a patient is a human suffering from a disease or condition that would benefit from treatment with tirzepatide.

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

[0606] Preparation #1 - Tirzepatide Composition Containing NaCl

[0607] The compositions were prepared essentially as described herein. 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 qs to a total final volume of 1 mL.

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

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

[0610] *Using 5mM phosphate buffer

[0611] Preparation #2 - Tirzepatide Composition Containing Propylene Glycol

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

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

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

[0615] *Using 5mM phosphate buffer

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

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

[0618]

[0619] The study also includes a 4-week follow-up period. In addition to safety and efficacy in treating T2DM, efficacy endpoints include the effects of tirzepatide on HbA1c, FBG, body weight, lipids, and waist circumference compared with placebo and dulaglutide 1.5 mg. The study also evaluated the effects of tirzepatide on GI tolerability, hypoglycemia, hypersensitivity reactions, and pancreatic safety, as well as the development of anti-drug antibodies during treatment. Model-based dose-response analyses were performed to predict the likelihood of significant HbA1c reduction and weight loss in longer-term studies.

[0620] Statistical analysis

[0621] Potency : The primary efficacy outcome of change in HbA1c from baseline to the 26-week endpoint was analyzed using a Bayesian dose-response model. The analysis was performed on the intention-to-treat population (mITT) analysis set. Supportive analysis of the primary efficacy outcome of the mITT dataset was based on body mass index (BMI) (<30 kg / m 2 , ≥30kg / m 2 ), metformin use, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline HbA1c as a covariate, and patient as a random effect.

[0622] Similar dose-effect models were used to analyze the mean change from baseline in weight at weeks 12 and 26, and the mean change from baseline in HbA1c at week 12, as in the primary analysis. Logistic regression with fixed effects for treatment and stratification and baseline as covariates was used to analyze the percentage of patients who achieved a weight loss of ≥5% or ≥10%, achieved an HbA1c target of ≤6.5% or ≤7.0% at week 26, or required rescue therapy. FBG (fasting blood glucose), SMBG (self-monitored blood glucose) levels, change from baseline in waist circumference, and mean percentage change from baseline to weeks 12 and 26 in lipids 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 = tirzepatide once weekly in the ascending-dose group, up to a maximum dose of 10 mg; LY 15 mg = tirzepatide once weekly in the ascending-dose group, up to a maximum dose of 15 mg; LOCF = last observation carried forward; N = number of patients; pbo = placebo; Week 26 = data during the mITT treatment period at Week 26, excluding data after study drug discontinuation or rescue drug initiation; mITT = modified intention-to-treat; SD = standard deviation. For Table 4, n = number of patients in the population with baseline and post-baseline values ​​at the specified time point. For Table 6, LY10 mg = tirzepatide once weekly in the ascending dose group, up to a maximum dose of 10 mg; ascending dose: (5 mg at Week 0 and Week 1), LY15 mg = tirzepatide once weekly in the ascending dose group, up to a maximum dose of 15 mg; ascending dose: (5 mg at Week 0 and Week 1; 10 mg from Week 2 to Week 5); N = number of patients in the designated group, m = number of patients who experienced a new event during the interval, FolUp = follow-up, T / Wk = time frame (weeks), and % = percentage of patients in the treatment group who experienced 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 the criteria; N is the number of patients in the population; % is the percentage of patients in the treatment group who experienced an event.

[0624] Table 3. HbA1c data

[0625]

[0626] The data in Table 3 support that tirzepatide at doses of 5 mg, 10 mg, and 15 mg significantly reduced HbA1c compared to baseline and was significantly different from placebo. A skilled artisan will appreciate that HbA1c values ​​of less than 5.7% are consistent with levels observed in non-diabetic patients. The tirzepatide dose group also differed significantly from dulaglutide 1.5 mg.

[0627] The percentages of patients achieving the HbA1c treatment target in Table 3 indicate that more patients receiving study drug in the tirzepatide 15 mg group achieved the treatment target of HbA1c ≤ 5.7% compared to any other treatment group.

[0628] Table 4. Mean fasting glucose values

[0629]

[0630] As expected from the observed changes in HbA1c, as shown in Table 4, the 5 mg, 10 mg, and 15 mg doses of tirzepatide significantly reduced fasting blood glucose compared to placebo and dulaglutide 1.5 mg.

[0631] Table 5. Weight loss

[0632]

[0633] Table 5 summarizes the proportions of patients who achieved target weight loss of ≥5%, ≥10%, and ≥15% at Week 26. Tirzepatide 5 mg, 10 mg, and 15 mg doses significantly reduced body weight compared to 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 studies, a higher percentage of patients in the tirzepatide 15 mg group were able to achieve a mean weight loss of more than 15%.

[0635] Table 6. Nausea, vomiting and diarrhea

[0636]

[0637] Table 6 illustrates the favorable effect on the incidence of gastrointestinal adverse events when using the proposed approach.

[0638] Table 7. Appetite reduction

[0639]

[0640] Decreased appetite is a centrally mediated effect. Table 7 presents data reported from clinical trials showing that tirzepatide has some centrally mediated effects. Centrally mediated tirzepatide activity may provide an additional therapeutic option for patients seeking treatment that provides 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 period of escalation. A 15 mg dose with a more acceptable tolerability profile is needed. Data from NCT03131687 support the 15 mg dose as the highest clinical maintenance dose encompassed by the present invention. The escalation regimen as claimed herein was studied to promote an acceptably tolerated 15 mg maintenance dose. See clinical study (NCT03311724) below.

[0642] Clinical study (NCT03311724) supports an incremental increase of 2.5

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

[0644]

[0645] Table 8. HbA1c Data at Week 12 - mITT Population for On-Treatment Dataset

[0646]

[0647]

[0648] LOCF = last observation carried forward; LY = tirzepatide; mITT = modified intention-to-treat; N = number of patients; pbo = placebo; Week 12: treated mITT at Week 12, excluding data after study drug discontinuation or initiation of rescue medication; LOCF Week 12: treated mITT, excluding data after study drug discontinuation or initiation of rescue medication, extrapolated to Week 12 using the last observation carried forward method.

[0649] As shown in Table 8, after 12 weeks of treatment (including an 8-week escalation phase), the placebo-adjusted changes in HbA1c from baseline were statistically significant and clinically meaningful for the 12 mg and 15 mg tirzepatide doses.

[0650] Table 9. Weight Loss Data at Week 12 - mITT Population for As-Treatment Dataset

[0651]

[0652]

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

[0654] As shown in Table 9, both tirzepatide doses were associated with significant weight reductions compared to placebo at week 12.

[0655] Table 10. Nausea, vomiting and diarrhea

[0656]

[0657]

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

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

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

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

[0662] m = number of patients who experienced a new event during the interval, where a new event is defined as a patient having a new onset of an event during this time period

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

[0664] As shown in Table 10, the most common adverse events were gastrointestinal, including nausea, vomiting, and diarrhea. The majority of these events were mild to moderate in severity. No patient discontinued the study due to gastrointestinal intolerance or any other adverse events.

[0665] Based on these data from NCT03311724, the use of an escalating dose schedule of 2.5 mg every 4 weeks is further supported.

[0666] biomarkers

[0667] Clinically 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 decrease in eGFR was observed at any dose. Clinical study laboratory measurements support the use of tirzepatide for the treatment of chronic kidney disease. Clinically relevant biomarkers were measured to assess and support the use of tirzepatide for the treatment of atherosclerosis. Clinically relevant triglyceride levels were reduced in all tirzepatide treatment groups. Clinical observations support the beneficial use of tirzepatide for the treatment of atherosclerosis.

[0668] Biomarkers predictive of NAFLD were observed during the clinical study to demonstrate the beneficial effects of tirzepatide in treating NAFLD. Biomarkers predictive of NASH were observed during the clinical study to demonstrate the beneficial effects of tirzepatide in treating NAFLD. HbA1c levels were measured during follow-up in tirzepatide-treated patients who achieved their blood sugar control goals and discontinued diabetes medications to verify the resolution of diabetes in these patients.

[0669] Example 1

[0670] Clinical dosing regimen

[0671] A clinical trial investigating three maintenance doses (5.0 mg, 10.0 mg, and 15.0 mg) of the present invention according to the dosing regimen of the present invention was conducted as follows.

[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 low-dose arm.

[0673] For the 10-mg group, the starting dose of tirzepatide was 2.5 mg once weekly for 4 weeks, followed by dose increases of 2.5 mg every 4 weeks (5 mg once weekly for 4 weeks, then 7.5 mg once weekly for four weeks) until the 10-mg dose was reached and maintained for 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 dose increases of 2.5 mg every 4 weeks (5 mg once weekly for 4 weeks, then 7.5 mg once weekly for 4 weeks, then 10 mg once weekly for 4 weeks, then 12.5 mg once weekly for 4 weeks) until the 15-mg tirzepatide dose was reached and maintained for the duration of the study. For patients who could not tolerate the 15-mg dose, the maintenance dose could be reduced to 10 mg.

[0675] Sequence

[0676] SEQ ID NO: 1

[0677] Tirzepatide

[0678] YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS

[0679] wherein X1 is Aib; X2 is Aib; K at position 20 is obtained by reacting the ε-amino group of the K side chain with (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)1-CO-(CH2) 18 The C-terminal amino acid was amidated to form a C-terminal primary amide.

Claims

1. Use of Tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating type 2 diabetes.

2. The method of claim 1, wherein the treatment comprises: 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 use of claim 2, wherein the ascending dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

4. The use of claim 2, wherein the ascending dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

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

6. Use of Tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the treatment of causing remission or regression of diabetes.

7. The method of claim 6, wherein the treatment comprises: 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. The use of claim 7, wherein the ascending dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

9. The use of claim 7, wherein the ascending dose is about 7.5 mg and the maintenance dose is about 10.0 mg.

10. The use of claim 7, wherein the escalating dose is about 12.5 mg and the maintenance dose is about 15.0 mg.

11. Use of Tirzepatide or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the prevention and treatment of diabetes.

12. The method of claim 11, wherein the treatment comprises: 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 use of claim 12, wherein the ascending dose is about 2.5 mg and the maintenance dose is about 5.0 mg.

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

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

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