Tirzepatide therapeutic methods

Abstract

To provide a pharmaceutical composition for treating high blood pressure.SOLUTION: Provided is a pharmaceutical composition for treating high blood pressure, comprising an effective amount of tirzepatide or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition is administered to the patient once weekly.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to the field of medicine. Refractory type 2 diabetes (T2DM) in patients who do not reach the target value 2D) is provided in a patient in need of increasing HDL-C levels. Methods relating to increasing HDL-C levels in A method of lowering blood pressure in a patient in need thereof is provided. [Brief description of the drawings]

[0002] [Figure 1] 1 graphically depicts HDL-C increases using efficacy estimands observed at 52 weeks in a clinical trial conducted substantially as described in Example 1. [Diagram 2] 1 is a graph showing the efficacy of Estimand in increasing HDL-C levels observed at 40 weeks in a clinical trial conducted substantially as described in Example 2. [Diagram 3] 1 is a graphical depiction of the reduction in systolic blood pressure in a clinical trial substantially as described in Example 1. [Figure 4] 1 is a graphical depiction of the reduction in diastolic blood pressure in a clinical trial substantially as described in Example 1. Detailed Description of the Invention

[0003] Glycated hemoglobin (HbA 1c ) is an important marker of glycemic control in diabetes American Diabetes Association (ADA) Guide The line indicates HbA below 5.7%. 1c indicates that patients with HbA 1cTreatment goals for patients may vary. HbA 1c Continued poor control of diabetes contributes disproportionately to the development of diabetes-related complications. Patients with type 2 diabetes are often treated using the ADA treatment paradigm. Despite this, normal blood sugar cannot be achieved. The ADA guidelines focus on diet, exercise, metformin, oral diabetes treatment, and then A reasonable HbA of 7% or less following current treatment options of basal insulin 1c Treatment goals However, many patients continue to experience high HbA 1c Goal They are unable to reach this stage and are considered to be suffering from refractory type 2 diabetes.

[0004] Refractory type 2 diabetes generally occurs on a background of (relatively stable) insulin resistance. In contrast, the disorder is caused by impaired insulin secretion or β-cell damage, which becomes increasingly severe over time. Patients who have been living with type 2 diabetes for at least 8 years are considered to have refractory type 2 diabetes. Therefore, patients with refractory type 2 diabetes are more likely to have There is a need for a method of treatment that provides normal or near-normal blood glucose levels in patients with refractory type 2 diabetes. A method of treatment for providing normal or near-normal blood glucose in a patient suffering from a diabetic disease. , in which the patient has been treating type 2 diabetes for at least 8 years, a treatment method is desired.

[0005] Nearly half of American adults have high blood pressure. High blood pressure is one of the leading causes of stroke, coronary heart disease, and stroke. Type 2 diabetes is a risk factor for cardiovascular disease (CHD), heart disease, and other serious health threats. Many patients who are also obese experience hypertension. Treatments typically have little or no effect on controlling hypertension. Treatment options for managing hypertension in diabetic patients are desirable. There are.

[0006] High-density lipoprotein cholesterol (HD) Low serum levels of LC) is another known risk factor for coronary heart disease (CHD). Patients with type 2 diabetes often experience low serum levels of HDL-C. However, Approved diabetes treatments generally fail to raise HDL-C. Longitudinal cohort Studies have established that HDL-C is inversely and independently associated with the risk of developing CHD. It has been recognized that HDL-C levels can be increased by pharmacotherapy. Therapeutic methods to raise HDL-C in affected patients are desirable.

[0007] The present invention relates to a method for treating, preventing, or delaying hypertension, comprising administering tirzepatide or The present invention further provides a method for treating type 2 diabetes comprising administering a pharma- ceutical acceptable salt of A method for treating, preventing or delaying hypertension in a patient diagnosed with hypertension comprising administering to said patient a therapeutically effective amount of The present invention provides a method comprising administering patide or a pharma- ceutically acceptable salt thereof.

[0008] The present invention provides a method for treating, preventing or delaying low HDL-C, comprising administering tirzepatide or The present invention further provides a method for treating a subject comprising administering to said subject a compound comprising the steps of: A method for treating, preventing, or delaying HDL-C in patients diagnosed with type 2 diabetes. and administering tirzepatide or a pharma- ceutically acceptable salt thereof to the patient. do.

[0009] The present invention is directed to treating refractory type 2 diabetes in patients who have had type 2 diabetes for at least 8 years. A method for preventing or delaying the onset of inflammatory bowel disease, comprising administering tirzepatide or a pharma- ceutical acceptable salt thereof to a patient in need thereof. The method includes administering

[0010] The present invention is directed to treating refractory type 2 diabetes in patients who have had type 2 diabetes for at least 8 years. The method includes administering tirzepatide or a pharma- ceutical acceptable salt thereof. Well, we provide a method.

[0011] In one embodiment, a patient in need of treatment for refractory type 2 diabetes has an HbA 1c has.

[0012] In one embodiment, a patient in need of treatment for refractory type 2 diabetes has an HbA 1c has.

[0013] In one embodiment, a patient in need of treatment for refractory type 2 diabetes has an HbA 1c In one embodiment, a patient in need of treatment for refractory type 2 diabetes is at least 5. HbA1C ≤ 7% 1c Have a therapeutic goal.

[0014] In one embodiment, a patient in need of treatment for refractory type 2 diabetes has an HbA 1c treatment Have a goal.

[0015] In one embodiment, a patient in need of treatment for refractory type 2 diabetes has an HbA 1c treatment Have a goal.

[0016] The present invention relates to metformin, SGLT-2, or metformin + SGLT-2 inhibitor. The present invention relates to a method for treating refractory type 2 diabetes in a patient who is non-responsive to tirzepatide or The present invention provides a method of administering a pharma- ceutically acceptable salt thereof.

[0017] Thus, one embodiment provides a method for treating, preventing, or slowing hypertension in a patient. A method for treating, preventing or delaying hypertension comprising administering to said patient an effective amount of tirzepatide or a pharmaceutical composition thereof. The method comprises administering to the patient a physiologically acceptable salt thereof once weekly. The present invention relates to a method for treating hypertension in a patient diagnosed with type 2 diabetes, the method comprising administering an effective amount of tirzepatin to a subject. The method includes administering to the patient once a week a compound such as benzodiazepine or a pharma- ceutical acceptable salt thereof.

[0018] In another aspect, the present invention provides a method for preventing or slowing hypertension in a patient, comprising administering to said patient an effective amount of The method includes administering to the patient once a week an amount of tirzepatide.

[0019] In another aspect, the present invention provides a method for preventing or slowing hypertension in patients diagnosed with type 2 diabetes. The method includes administering a therapeutically effective amount of tirzepatide to a patient once a week. Provide.

[0020] In another aspect, the present invention provides a method for treating, preventing or delaying the onset of hypertension in a patient. Use of tirzepatide for preparing a medicament, the medicament being administered once a week. to provide.

[0021] The present invention provides a method for treating, preventing or slowing hypertension comprising administering to a subject an effective amount of tirzepa and administering to a patient in need of such treatment a medicament for the treatment of atopic dermatitis. The present invention provides a method comprising:

[0022] In one embodiment, the patient in need of treatment for hypertension has type 2 diabetes, and Not obese.

[0023] In one embodiment, the patient in need of treatment for hypertension has type 2 diabetes, and Being obese.

[0024] In one embodiment, the patient in need of treatment for hypertension suffers from refractory type 2 diabetes. .

[0025] In one embodiment, the patient in need of treatment for hypertension has been suffering from type 2 diabetes for at least 8 years. I am infected.

[0026] Thus, one embodiment provides for treating hypertensive crisis in patients with refractory type 2 diabetes, A method for preventing or delaying the onset of tirzepatide, comprising administering to said patient an effective amount of tirzepatide or a pharma- ceutical acceptable salt thereof. The method includes administering to the patient an acceptable salt once a week.

[0027] In one embodiment, the patient in need of treatment for hypertensive crisis suffers from type 2 diabetes. and are non-obese.

[0028] In one embodiment, the patient in need of treatment for hypertensive crisis suffers from type 2 diabetes. and are obese.

[0029] In one embodiment, the patient in need of treatment for hypertensive crisis suffers from refractory type 2 diabetes. is doing.

[0030] In one embodiment, a patient in need of treatment for hypertensive crisis has been diagnosed with type 2 hypertension for at least 8 years. If you have diabetes.

[0031] Thus, one embodiment provides a method for treating, preventing, or delaying the onset of low HDL-C in a patient. The method comprises administering an effective amount of tirzepatide or a pharma- ceutical acceptable salt thereof to a patient once a week. The method includes administering to a subject.

[0032] In another aspect, the invention is a method for preventing or delaying a hypertensive crisis in a patient. Therefore, an effective amount of tirzepatide or a pharma- ceutically acceptable salt thereof is administered to the patient once a week. The present invention provides a method comprising:

[0033] In another aspect, the invention is a method for preventing or delaying low HDL-C in a patient. and administering an effective amount of tirzepatide or a pharma- ceutical acceptable salt thereof to a patient once a week. The present invention provides a method, including:

[0034] In another aspect, the present invention provides a method for administering oral For treating hypertension in patients undergoing clinical treatment for type 2 diabetes with antidiabetic drugs The method includes administering to a patient an effective amount of tirzepatide or a pharma- ceutical acceptable salt thereof, the method comprising ... The method includes administering to the patient once a week a salt thereof comprising administering to the patient once a week

[0035] In another aspect, the present invention relates to a method for treating type 2 diabetes mellitus. 4. A method for improving glycemic control in a patient at risk for hypertension, comprising administering an effective amount of tirzepatide or a pharma- ceutically acceptable salt thereof is administered to a patient once a week, Methods are provided that provide a reduced risk of experiencing a hypertensive crisis.

[0036] In another aspect, the present invention provides a method for treating type 2 diabetes mellitus and at risk for hypertension. A method for improving glycemic control in a patient, comprising administering to said patient an effective amount of tirzepatide or a pharmacologic equivalent thereof. administering an acceptable salt to the patient once a week for at least 30 weeks, A method is provided that provides a reduced risk of experiencing Rheumatoid Arthritis.

[0037] In another aspect, the present invention relates to weight management in patients who are obese and at risk for hypertension. A method for improving the treatment of rheumatoid arthritis, comprising administering an effective amount of tirzepatide or a pharma- ceutical acceptable salt thereof once a week. and administering to the patient a single dose of the active ingredient in the compound, the active ingredient providing a reduction in the risk that the patient will experience a hypertensive crisis. , a method is provided.

[0038] In another aspect, the invention provides a method for treating hypertension in a patient, comprising administering to said patient an effective amount of tirzepatide or a pharma- ceutical acceptable salt thereof is administered to a patient once a week, wherein the weight is within the normal weight range for the patient.

[0039] In another aspect, the present invention relates to weight management in patients who are obese and at risk for hypertension. A method for improving the treatment of rheumatoid arthritis, comprising administering an effective amount of tirzepatide or a pharma- ceutical acceptable salt thereof once a week. and administering to the patient a dose of 100 mg ... , a method is provided.

[0040] In another aspect, the present invention provides a method for treating, preventing or delaying the onset of a hypertensive crisis. Tirzepatide or a pharma- ceutical acceptable salt thereof for use in a patient, or a pharma- ceutically acceptable salt thereof is administered once a week; The salt is preferably

[0041] In another aspect, tirzepa for use in treating, preventing or delaying the onset of hypertension. Tirzepatide or a pharma- ceutically acceptable salt thereof, The salt provides tirzepatide, or a pharma- ceutically acceptable salt thereof, administered once weekly.

[0042] In another aspect, one embodiment provides a pharmaceutical composition for treating, preventing or delaying the onset of hypertension. Use of tirzepatide or a pharma- ceutically acceptable salt thereof for preparing a medicament, comprising The product is administered once weekly.

[0043] In another aspect, a medicament for treating, preventing or delaying the onset of hypertension is prepared. The use of tirzepatide for the treatment of rheumatoid arthritis, wherein the pharmaceutical agent is administered once a week, is provided.

[0044] In another aspect, an embodiment treats, prevents, or delays the onset of a hypertensive crisis. Use of tirzepatide or a pharma- ceutically acceptable salt thereof for the preparation of a medicament for The medication is administered once a week.

[0045] In another aspect, the present invention relates to a pharmaceutical composition for treating, preventing or delaying the onset of a hypertensive crisis. Use of tirzepatide for the preparation of a pharmaceutical composition, the pharmaceutical being administered once a week, do.

[0046] U.S. Patent No. 9,474,780 describes and claims tirzepatide. As used herein, the term "tirzepatide" refers to the compound having the amino acid sequence of SEQ ID NO:1. Any GIP / GLP-1 receptor agonist and the party seeking approval of such protein whether the author actually identified the protein as tirzepatide or some other Regardless of the terminology used, will depend, in whole or in part, on the data regarding tirzepatide submitted to regulatory authorities by Any drug that is the subject of a regulatory submission seeking approval of a GIP / GLP-1 receptor agonist product Tirzepatide acts on the GIP / GLP-1 receptor and inhibits insulin secretion. This results in stimulation of the synthesis and secretion of ketamine, providing improved glycemic control in T2DM patients. It is shown that:

[0047] As used herein, "hypertensive crisis" refers to a condition in which blood pressure becomes dangerously high and affects the patient's system. A hypertensive crisis typically involves at least one 80 / 120. Hypertension is generally defined as a systolic / diastolic pressure of 130 / 80. be.

[0048] As used herein, "refractory type 2 diabetes" refers to diabetes that is not treated with oral standard treatments such as metformin. Using drugs to increase HbA 1c Refers to patients who are unable to achieve their goals.

[0049] As used herein, "HbA 1c The "goals" are determined by the patient's clinical treatment plan. The desired mean achieved by the patient, as measured using clinically accepted methods. HbA 1c Current ADA guidelines focus on diet, exercise, and metformin. 7% or less of the current treatment options of oral diabetes treatment followed by basal insulin were Reasonable HbA 1c However, many patients are not able to achieve clinical treatment. Regardless of HbA 1c I am unable to reach my goal and I am considered to have intractable type 2 diabetes. In one embodiment, HbA 1c The goal is 7% or less. 1c The target is below 5.7%.

[0050] No CHD at baseline in the Framingham study (12-year follow-up period) Participants with high HDL-C levels (80th percentile) among men and women aged 49-82 years ) had a greater cardiovascular risk compared to participants with low HDL-C levels (20th percentile) The risk of the event was 50 percent lower 2 Prospective Cardiova The PROCAM study (approximately 4,500 volunteers, Ages 16-65, followed for 6 years) individuals with HDL-C < 35 mg / dl have a 4-fold higher coronary risk than individuals with HDL-C ≥ 35 mg / dl. Assmann G et al.,High-density liquid poprotein cholesterol as a predictor of coronary heart disease risk.The PROCAM e xperience and pathophysiological implica tions for reverse cholesterol transport. Atherosclerosis.1996;124(Suppl):S11-S20 Gordon et al. found that for every 1 mg / dl increase in HDL-C, suggested a 2-3 percent reduction in cardiovascular risk. Gordon DJ et al. al.High-density lipoprotein cholesterol and cardiovascular disease: four prospects tive American studies.Circulation.1989;7 9:8-15. Veterans Administration HDL Inter Results from the Vascular Invasion Trial (VA-HIT) showed that In patients with pulmonary hypertension, a modest increase in HDL-C of just 6 percent was associated with increased risk of coronary morbidity and mortality. Rubins H showed that the pulmonary circulation reduced both the risk of infection and mortality by 24 percent. B,et al.,Gemfibrozil for the secondary p recurrence of coronary heart disease in m en with low levels of high-density lipop rotein cholesterol.Veterans Affairs High -Density Lipoprotein Cholesterol Interve ntion Trial Study Group.N Engl J Med.199 9;341:410-8.

[0051] Current treatments for increasing HDL-C include increasing exercise and reducing dietary fat. This can include lifestyle modifications. In many cases, lifestyle modifications will achieve the desired increase in HDL-C. There are currently insufficient treatment options for patients who need to increase HDL-C. There is a need for therapies that treat, prevent, or delay low HDL-C.

[0052] As used herein, the terms "treatment," "treat," "treating," and the like refer to It is meant to include slowing or attenuating the progression of a disease, condition, or disorder. These terms are used to refer to the condition or disorder even if the condition or disorder is not actually eliminated. Alleviating one or more symptoms of a disorder or condition, even if the progression itself is not slowed or reversed; This also includes ameliorating, attenuating, eliminating or alleviating.

[0053] As used herein, the terms "prevent," "preventing," "prevention," and the like refer to It is meant to include the avoidance of the onset of a disease, condition, disorder or symptom.

[0054] As used herein, the terms "delay", "delaying" and the like refer to a disease, It is meant to include increasing the time period until the onset of a condition, disorder or symptom.

[0055] When used herein in reference to multiple outcomes, the term "composite" refers to any one of the outcomes. refers to the occurrence of the first of any of the following:

[0056] The term "increase in HDL-C" refers to an increase in measured HDL-C levels from baseline to In one embodiment, the change in increase in HDL-C is statistically significant. In one embodiment, the increase in HDL-C is an increase of more than 2% from baseline. In one embodiment, the increase in HDL-C is greater than a 5% increase from baseline. In one embodiment, the increase in HDL-C is an increase of more than 7% from baseline. In some embodiments, the increase in HDL-C is greater than 10% increase from baseline.

[0057] A "therapeutically effective amount" refers to the amount of tirzepatide or its derivatives for the method or use of the present invention. or a physiologically acceptable salt thereof, or a compound thereof for use in the method or use of the present invention. and providing to a researcher, physician, or other clinician an amount of a pharmaceutical composition comprising a pharma- ceutical acceptable salt of Thus, the biological or medical response of the patient that is being sought or the desired therapeutic effect in the patient. The effective amount of tirzepatide or its pharma- ceutical acceptable salts is defined as the amount that will induce the desired effect. The amount will depend on the disease state, age, sex, and weight of the individual, and on the amount that will elicit a desired response in the individual. The effective amount may vary depending on factors such as the ability of tirzepatide to produce a therapeutically beneficial effect. In certain embodiments, the methods described herein provide an amount that outweighs any toxic or detrimental effects. The therapeutically effective amount of tirzepatide or a pharma- ceutical acceptable salt thereof for use in and 15 mg. In certain embodiments, tirzepatide or its derivatives are A therapeutically effective amount of a physiologically acceptable salt is 5.0 mg. The therapeutically effective amount of tide or a pharma- ceutically acceptable salt thereof is 10.0 mg. In this embodiment, the therapeutically effective amount of tirzepatide or a pharma- ceutical acceptable salt thereof is 15.0 mg. do.

[0058] Additional embodiments are described below.

[0059] In one embodiment, the present invention provides a method for improving glycemic control in patients with type 2 diabetes mellitus and decreasing HDL-C. The present invention relates to a method for increasing the amount of tirzepatide or a pharma- ceutical acceptable salt thereof, the method comprising administering tirzepatide or a pharma- ceutical acceptable salt thereof in a therapeutically effective amount. administering to the patient once a week for at least 30 weeks.

[0060] In one embodiment, tirzepatide or a pharma- ceutically acceptable salt thereof is administered for at least 40 weeks. In one embodiment, tirzepatide or a pharma- ceutically acceptable salt thereof is administered will also be administered for 52 weeks.

[0061] Hypertension and normal HbA 1c blood sugar 1. A method for treating, preventing or delaying the onset of hypertension in a patient, comprising administering to a subject a therapeutically effective amount of The method comprises administering tirzepatide or a pharma- ceutical acceptable salt thereof to a patient once a week. In one embodiment, the hypertension is selected from the group consisting of hypertension and hypertensive crisis.

[0062] A method for preventing or slowing hypertension in a patient, comprising administering to said patient a therapeutically effective amount of tirzepatide or comprising administering to the patient a pharma- ceutically acceptable salt thereof once a week.

[0063] Improve glycemic control in patients diagnosed with type 2 diabetes mellitus and treat and prevent hypertension in patients The present invention relates to a method for preventing or delaying inflammatory bowel disease, the method comprising administering a therapeutically effective amount of tirzepatide or a pharma- ceutical acceptable salt thereof to a subject. administering the salt to the patient once a week.

[0064] In one embodiment, the method reduces the risk that the patient will experience hypertension. In one embodiment, the method reduces the risk of the patient experiencing a hypertensive crisis. In the method, the risk of the patient experiencing clinically low HDL-C is reduced.

[0065] A method for improving glycemic control in a patient suffering from type 2 diabetes mellitus, comprising administering to said patient a therapeutically effective amount of The method comprises administering to a patient once a week an effective amount of tirzepatide or a pharma- ceutical acceptable salt thereof. , the method reduces the risk that the patient will experience hypertension.

[0066] The method according to any of the above embodiments, wherein the patient is suffering from type 2 diabetes mellitus. The method according to any of the above embodiments, wherein the patient is suffering from refractory type 2 diabetes. The method according to any of the above embodiments, wherein the patient has been suffering from diabetes for at least 8 years. The method according to any of the above embodiments, wherein the patient has been suffering from type 2 diabetes for at least 10 years. The method according to any of the above embodiments, wherein the administration of tirzepatide continues for at least 40 weeks. The method of any of the above embodiments, wherein the patient is non-obese.

[0067] The patient has one or more of T2DM, hypertension, reduced HDL-C and obesity. 2. The method according to any of the above embodiments.

[0068] In one embodiment, the patient has multiple cardiovascular risk factors without hypertension or clinically significant have either hypertension or

[0069] In one embodiment, the patient has multiple cardiovascular risk factors or an HbA1c level greater than 11%. The device has either

[0070] As used herein, a "cardiovascular risk factor" refers to current tobacco use (any form of tobacco use); at least one prescription drug to treat hypercholesterolemia within the past 6 months Use of approved lipid modifying therapy or reported untreated Low-density lipoprotein cholesterol (LDL) -C) ≥ 3.4 mmol / L (100 mg / dL); within the past 6 months, no reported treatment For treated or untreated men, <1.0 mmol / L (40 mg / dL) and and for women, high-density lipoprotein cholesterol levels below 1.3 mmol / L (50 mg / dL). cholesterol (HDL-C) or triglycerides ≧ 2.3 mmol / L (150 mg / dL); use of at least one blood pressure medication to treat hypertension or untreated systolic blood pressure Systolic blood pressure (SBP) ≧ 130mmHg or diastolic blood pressure (DBP) stolic blood pressure (DBP) ≥ 80mmHg; 102cm for men; for waist circumference measured at 88 cm; means.

[0071] As used herein, "non-obese" refers to a patient who is not obese by applicable standards. In one embodiment, a non-obese patient has a body mass index of less than 30 BMI.

[0072] As used herein, "co-occurring" refers to a condition in which a patient has two or more medical conditions. This means being diagnosed with

[0073] In one embodiment, the patient's risk of hypertensive crisis is reduced by at least about 14%.

[0074] In one embodiment, the patient's risk of hypertensive crisis is reduced by at least about 10%.

[0075] In one embodiment, HDL-C levels are increased. In one embodiment, the level of ketamine is increased to a clinically desirable level. The present invention relates to a method for improving glycemic control and increasing HDL-C in a patient suffering from cerebrovascular disease, the method comprising administering tirzepatide or administering a therapeutically effective amount of a pharma- ceutically acceptable salt thereof to a patient once a week for at least 30 weeks The method includes:

[0076] In one embodiment, the risk of complication of hospitalization or death due to hypertension is reduced.

[0077] In one embodiment, the risk of death or hospitalization due to hypertension is reduced by administering an effective amount of tirzepatide or its equivalent. is reduced in patients treated with a pharma- ceutically acceptable salt of

[0078] In one embodiment, the risk of concomitant hypertension and HbA1c above 5.7% is reduced. In embodiments, the risk of the co-occurring low HDL-C, high blood pressure, and HbA1c above 7% is reduced. do.

[0079] In one embodiment, the risk of having low HDL-C, high blood pressure, and HbA1c greater than 5.7% is determined by: is reduced.

[0080] In one embodiment, the risk of having low HDL-C, high blood pressure, and HbA1c greater than 6% is reduced. will be done.

[0081] A method for normalizing HbA1c blood glucose levels in patients with refractory type 2 diabetes. Thus, a therapeutically effective amount of tirzepatide or a pharma- ceutically acceptable salt thereof is administered to a patient once a week. The method of claim 1,

[0082] In one embodiment, the amount of tirzepatide is about 5.0 mg, about 10.0 mg, and about 15.0 mg. In one embodiment, the amount of tirzepatide is selected from the group consisting of about 7.5 mg and and about 12.5 mg.

[0083] In one embodiment, the amount of tirzepatide is about 5.0 mg.

[0084] In one embodiment, the amount of tirzepatide is about 10.0 mg.

[0085] In one embodiment, the amount of tirzepatide is about 15.0 mg.

[0086] In one embodiment, the dose of tirzepatide is about 5.0 mg.

[0087] In one embodiment, the dose of tirzepatide is about 10.0 mg.

[0088] In one embodiment, the dose of tirzepatide is about 15.0 mg.

[0089] In one embodiment, tirzepatide or a pharma- ceutically acceptable salt thereof is administered in a dose escalation protocol. It is administered using

[0090] In one embodiment, the patient is receiving treatment with tirzepatide or a pharma- ceutically acceptable salt thereof. Prior to this, patients had been taking one or two oral antidiabetic drugs for at least one year, but had an HbA1C < 7. % cannot be achieved.

[0091] In one embodiment, the patient is receiving treatment with tirzepatide or a pharma- ceutically acceptable salt thereof. Prior to this, patients had achieved HbA1C < 8% with one or two oral medications for at least one year. It cannot be achieved.

[0092] In one embodiment, the patient is receiving treatment with tirzepatide or a pharma- ceutically acceptable salt thereof. Prior to this, patients had maintained HbA1C < 10% with the use of one or two oral medications for at least one year. Unattainable.

[0093] In one embodiment, the once weekly administration of tirzepatide or a pharma- ceutically acceptable salt thereof is In one embodiment, the administration of tirzepatide or a pharma- ceutically acceptable salt thereof is continued for at least 30 weeks. The weekly administration of the salt is continued for at least 40 weeks. The weekly administration of the pharma- ceutically acceptable salt is continued for at least 50 weeks. In one embodiment, once-weekly administration of tirzepatide or a pharma- ceutically acceptable salt thereof is effective for at least 2 In one embodiment, tirzepatide or a pharma- ceutically acceptable salt thereof is administered once a week for a period of one year. The administration of tirzepatide or its pharmaceutical equivalents is continued for at least three years. Weekly administration of an acceptable salt for is continued for at least 5 years.

[0094] In one embodiment, the dose of tirzepatide is 15 mg / week. The dose of tirzepatide is 10 mg / week. In one embodiment, the dose of tirzepatide is 5 mg / week. g / week.

[0095] In one embodiment, the patient is diagnosed with type 2 diabetes due to administration of tirzepatide or its pharmacological At least 8 years prior to administration of acceptable salts.

[0096] In one embodiment, the patient receiving tirzepatide or a pharma- ceutically acceptable salt thereof is a type 2 The diagnosis of diabetes mellitus occurred at least 10 years before tirzepatide administration.

[0097] In one embodiment, the patient receiving tirzepatide or a pharma- ceutically acceptable salt thereof is a type 2 The diagnosis of diabetes mellitus occurred at least 13 years prior to the administration of tirzepatide.

[0098] In one embodiment, the patient receiving tirzepatide or a pharma- ceutically acceptable salt thereof is He is at least 46 years old.

[0099] In one embodiment, the patient receiving tirzepatide or a pharma- ceutically acceptable salt thereof is He must be at least 55 years old.

[0100] In one embodiment, the patient receiving tirzepatide or a pharma- ceutically acceptable salt thereof is At least 60 years old.

[0101] In one embodiment, the patient receiving tirzepatide or a pharma- ceutically acceptable salt thereof is Oral toformin and SGLT2 drugs are also administered.

[0102] In one embodiment, the patient receiving tirzepatide or a pharma- ceutically acceptable salt thereof is Oral GLT2 drugs are also administered.

[0103] In one embodiment, the patient receiving tirzepatide or a pharma- ceutically acceptable salt thereof is Toformin is also administered.

[0104] In one embodiment, the patient receiving tirzepatide or a pharma- ceutically acceptable salt thereof is Basal insulin is also administered.

[0105] In one embodiment, the patient receiving tirzepatide or a pharma- ceutically acceptable salt thereof is Toformin and basal insulin are also administered.

[0106] In one embodiment, the patient receiving tirzepatide or a pharma- ceutically acceptable salt thereof is GLT2 and basal insulin are also administered.

[0107] In one embodiment, the patient receiving tirzepatide or a pharma- ceutically acceptable salt thereof is Toformin, SGLT2 and basal insulin are also administered.

[0108] In one embodiment, the basal insulin is insulin glargine.

[0109] In one embodiment, the basal insulin is insulin degludec.

[0110] In one embodiment, the patient receiving tirzepatide or a pharma- ceutically acceptable salt thereof is Oral GLT2 medications are also administered.

[0111] In one embodiment, the patient receiving tirzepatide or a pharma- ceutically acceptable salt thereof is Toformin, oral SGLT2, and insulin degludec are also administered.

[0112] In one embodiment, the patient receiving tirzepatide or a pharma- ceutically acceptable salt thereof is Toformin, oral SGLT2, and insulin degludec are also administered.

[0113] In one embodiment, the patient receiving tirzepatide or a pharma- ceutically acceptable salt thereof is Toformin, oral SGLT2, and insulin glargine are also administered.

[0114] In one embodiment, the patient receiving tirzepatide or a pharma- ceutically acceptable salt thereof is Toformin and insulin glargine are also administered.

[0115] Tirzepatide or a pharma- ceutically acceptable salt thereof for use in any of the above embodiments. .

[0116] Tirzepatide or its derivatives in the preparation of a medicament for any of the above embodiments. Use of biologically acceptable salts.

[0117] Further embodiments are described in the following examples, which are to be construed as limiting. It's not something like that.

[0118] One embodiment provides a compound comprising: Tirzepatide or a pharma- ceutically acceptable salt thereof, The acceptable salt is administered once a week. Further embodiments include the use of chilli powder to treat hypertension in patients diagnosed with type 2 diabetes. Zepatide or a pharma- ceutically acceptable salt thereof, The salt is administered once a week, providing tirzepatide or a pharma- ceutically acceptable salt thereof.

[0119] In another embodiment, the present invention provides a method for preventing or delaying hypertension in a patient. Tirzepatide or a pharma- ceutically acceptable salt thereof for use in a patient with a rheumatoid arthritis, The tirzepatide or pharma- ceutically acceptable salt thereof is administered once weekly. In one embodiment, the patient has been diagnosed with type 2 diabetes. The patient has type 2 diabetes and is non-obese. In a further embodiment, the patient is suffering from refractory type 2 diabetes and is obese. In another further embodiment, the patient has been suffering from type 2 diabetes for at least 8 years. is suffering from.

[0120] In another embodiment, the present invention provides a method for treating, preventing, or delaying the onset of a hypertensive crisis in a patient. 2. The method of claim 1, further comprising administering to said patient a therapeutically effective amount of tirzepatide or a pharma- ceutical acceptable salt thereof, Tirzepatide or a pharma- ceutically acceptable salt thereof is administered once a week. In one embodiment, the patient has been diagnosed with type 2 diabetes. In another embodiment, the patient has type 2 diabetes and is non-obese. In a further embodiment, the patient has type 2 diabetes and is obese. In another further embodiment, the patient is suffering from refractory type 2 diabetes. I have had type 2 diabetes for 8 years.

[0121] In another embodiment, the present invention provides a method for treating, preventing, or delaying the onset of low HDL-C in a patient. Tirzepatide or a pharma- ceutical acceptable salt thereof for use in administering Tirzepatide or a pharma- ceutically acceptable salt thereof is administered once a week; Acceptable salts are provided.

[0122] In another embodiment, the present invention provides a method for preventing or delaying the onset of low HDL-C in a patient. Tirzepatide or a pharma- ceutically acceptable salt thereof for use in Tirzepatide or its pharma- ceutical acceptable salt is administered once a week. The present invention provides a salt that can be used in the preparation of a food product.

[0123] In another embodiment, the present invention provides an oral anti-inflammatory drug for at least 1 year, 2 years, 3 years, 4 years, or 5 years. For use in the treatment of hypertension in patients receiving clinical treatment for type 2 diabetes with antidiabetic agents Tirzepatide or a pharma- ceutical acceptable salt thereof, wherein the patient's HbA1c is more than 7%. Tirzepatide or a pharma- ceutical acceptable salt thereof is administered once a week. provides pharma- ceutically acceptable salts thereof.

[0124] In another embodiment, the present invention provides a method for treating type 2 diabetes mellitus and at risk for hypertension. Tirzepatide or a pharmaceutical equivalent thereof for use in improving glycemic control in a patient and an acceptable salt thereof, wherein tirzepatide or a pharma- ceutically acceptable salt thereof is administered once a week. In one embodiment, tirzepatide or a pharma- ceutically acceptable salt thereof is provided. The compound, or a pharma- ceutical acceptable salt thereof, is administered once a week for at least 30 weeks.

[0125] In another embodiment, the present invention relates to a method for treating obesity and hypertension in a patient who is obese and at risk for hypertension. Tirzepatide or a pharma- ceutical acceptable salt thereof for use in improving weight control. Tirzepatide or a pharma- ceutically acceptable salt thereof is administered once a week. Pharmaceutically acceptable salts thereof are provided.

[0126] In another embodiment, the present invention provides a method for treating hypertension in a patient comprising administering tirzepatide to a subject. tirzepatide or a pharma- ceutical acceptable salt thereof is administered once a week, and the patient's weight is within the normal weight range for the patient, or a pharma- ceutically acceptable salt thereof. In another embodiment, the present invention provides: do.

[0127] Embodiment 1. Tirzepatide or or a pharma- ceutical acceptable salt thereof, Tirzepatide or a pharma- ceutically acceptable salt thereof is administered once weekly.

[0128] Embodiment 2. Tirzepatide or a pharmaceutical composition thereof for use in treating hypertension in a patient. and the tirzepatide or a pharma- ceutically acceptable salt thereof is administered once a week. Tirzepatide or a pharma- ceutically acceptable salt thereof is administered.

[0129] Embodiment 3. Tirzepatide for use in increasing HDL-C in a patient. or a pharma- ceutically acceptable salt thereof, The salt is administered once weekly; tirzepatide or a pharma- ceutically acceptable salt thereof.

[0130] Embodiment 4. The patient has had type 2 diabetes for at least 8 years. 3. Tirzepatide or a pharma- ceutically acceptable salt thereof for use according to any one of the above items.

[0131] Embodiment 5. HbA 1c Any of embodiments 1 to 4, the goal being less than 7% Tirzepatide or a pharma- ceutically acceptable salt thereof for the use described in 1.

[0132] Embodiment 6. The patient's HbA 1c The target is 5.7% or less. Tirzepatide or a pharma- ceutically acceptable salt thereof for use according to any one of the preceding claims.

[0133] Embodiment 7. HbA 1c Any one of embodiments 1 to 6, wherein the 2. Tirzepatide or a pharma- ceutically acceptable salt thereof for use according to the above.

[0134] Embodiment 8. HbA 1c Any one of embodiments 1 to 7, wherein the 2. Tirzepatide or a pharma- ceutically acceptable salt thereof for use according to the above.

[0135] Embodiment 9. The method of any one of embodiments 1 to 8, wherein the patient is at least 46 years old. 2. Tirzepatide or a pharma- ceutically acceptable salt thereof for use according to claim 1.

[0136] Embodiment 10. Any of embodiments 1 to 9, wherein the patient is at least 60 years old. Tirzepatide or a pharma- ceutically acceptable salt thereof for the use described in 1.

[0137] Embodiment 11. Any of embodiments 1 to 10, wherein the patient is taking an SGLT2 inhibitor. Tirzepatide or a pharma- ceutically acceptable salt thereof for use according to any one of the preceding claims.

[0138] Embodiment 12. Any of embodiments 1 to 11, wherein the patient is taking metformin. Tirzepatide or a pharma- ceutically acceptable salt thereof for the use described in 1.

[0139] Embodiment 13. The method of any one of embodiments 1 to 12, wherein the patient is not receiving basal insulin. Tirzepatide or a pharma- ceutically acceptable salt thereof for use according to any one of the above.

[0140] Embodiment 14. The patient is taking metformin and an SGLT2 inhibitor, but is not receiving H bA 1c For the use according to any one of embodiments 1 to 13, which does not meet the target Tirzepatide or a pharma- ceutically acceptable salt thereof.

[0141] Embodiment 15. The tirzepatide or a pharma- ceutical acceptable salt thereof is administered for at least 40 weeks. Tirzepatide or and pharma- ceutically acceptable salts thereof.

[0142] Embodiment 16. The tirzepatide or a pharma- ceutical acceptable salt thereof is administered for at least 50 weeks. Tirzepatide or and pharma- ceutically acceptable salts thereof.

[0143] Embodiment 17. The tirzepatide or a pharma- ceutical acceptable salt thereof is administered for at least 2 years. Tirzepatide or its derivatives for use according to any one of embodiments 1 to 16 are administered. A pharma- ceutically acceptable salt of

[0144] Embodiment 18. The method according to any one of embodiments 1 to 17, wherein the patient is non-obese. Tirzepatide or a pharma- ceutically acceptable salt thereof for use in the treatment of chronic conditions.

[0145] Embodiment 19. The weekly dose of tirzepatide or a pharma- ceutical acceptable salt thereof is 5 mg / kg. g of tirzepatide or its derivatives for use according to any one of embodiments 1 to 18. Pharmaceutically acceptable salts.

[0146] Embodiment 20. The weekly dose of tirzepatide or a pharma- ceutical acceptable salt thereof is 10 tirzepatide or its derivatives for use according to any one of embodiments 1 to 18, A pharma- ceutically acceptable salt of

[0147] Embodiment 21. The weekly dose of tirzepatide or a pharma- ceutical acceptable salt thereof is 15 tirzepatide or its derivatives for use according to any one of embodiments 1 to 18, A pharma- ceutically acceptable salt of

[0148] Embodiment 22. The patient is a patient having hypertension. 2. Tirzepatide or a pharma- ceutically acceptable salt thereof for use according to claim 1.

[0149] Embodiment 23. The method according to any one of embodiments 1 to 22, wherein the patient also has low HDL-C. Tirzepatide or a pharma- ceutically acceptable salt thereof for use according to any one of the preceding claims.

[0150] Embodiment 24. The method of any one of embodiments 1 to 17 or 19 to 22, wherein the patient is also obese. Tirzepatide or a pharma- ceutically acceptable salt thereof for use according to any one of the above.

[0151] Embodiment 25. The patient has at least two cardiovascular risk factors, 21. Tirzepatide or a pharma- ceutically acceptable salt thereof for use according to any one of claims 1 to 21.

[0152] Embodiment 26. Any of embodiments 1 to 21, wherein the patient has no cardiovascular risk factors. Tirzepatide or a pharma- ceutically acceptable salt thereof for the use described in 1.

[0153] Embodiment 27. The patient has had type 2 diabetes for at least 10 years. Tirzepatide or a pharma- ceutically acceptable salt thereof for use according to any one of aspects 1 to 26. Salt.

[0154] As used herein, "estimand" means a measure that results from a requirement by a particular regulatory agency. The efficacy and treatment regimen of tirzepatide will be evaluated to determine its efficacy in treating Efficacy Use Estimand before discontinuing study drug or for persistent severe hyperglycemia. To evaluate the outcome in humans before starting salvage therapy for - Required by certain regulatory agencies, including the U.S. Food and Drug Administration, access to tirzepatide Regardless of adherence or the introduction of rescue therapy for persistent severe hyperglycemia, The therapeutic effects in humans will be evaluated. EXAMPLES

[0155] Example 1. Clinical trial using tirzepatide The enrollment criteria, described in Table 1 below, are similar to patients seen in a typical diabetes practice. The study included participants with type 2 diabetes who were refractory to oral treatment. The study is designed to include older patients. The average duration of type 2 diabetes is about 8 years. The trial will last for 52 weeks.

[0156] [Table 1]

[0157] The study consisted of a screening visit followed by a single-blind, 3-week placebo run-in period. Patients were then administered tirzepatide at 5, 10 or 15 mg (titrated (administered using standard titration protocol) or insulin degludec (standard titration protocol) Patients receiving insulin degludec will be randomized and followed at approximately monthly intervals. Standard insulin degludec titration protocols will be followed during the study. Blood pressure measurements at each visit and serum creatinine at baseline and week 52 were performed using standard clinical methods. Blood pressure measurements using the method of Example 1 are shown in Figures 3 and 4. HDL-C levels using the method of Example 1 are shown in FIG.

[0158] Up to 92.6 percent of participants treated with tirzepatide had a diabetes-free survival rate as determined by the American Diabetes Association. The recommended target for patients with idiopathic pulmonary disease is less than 7 percent HbA 1c In the test, Up to 48.5 percent of participants who received tirzepatide had a lower H bA 1c - levels seen in non-diabetic people.

[0159] [Table 2]

[0160] The mean insulin degludec dose at week 52 was 48.8 units per day.

[0161] Example 2. Clinical trial using tirzepatide The enrollment criteria shown in Table 3 below were patients considered to be refractory to oral treatment for type 2 diabetes. However, oral diabetes treatment will be continued throughout the study. The duration is approximately 13 years. The trial will last for 40 weeks.

[0162] Clinical Trial 2, Table 3

[0163] [Table 3]

[0164] The study was designed to consist of a screening visit followed by a 3-week run-in period. Patients were then treated with insulin glargine with or without metformin. 40 mg of tirzepatide 5, 10 or 15 mg or placebo as an add-on to treatment The study will begin a two-week randomized, double-blind trial. The dose of insulin glargine will be determined based on a validated Uses a treat-to-target algorithm Patients were titrated throughout the study at approximately weekly intervals and then The study protocol included blood pressure measurements at each visit using standard clinical methods. , and serum lipid profiles at baseline and 40 weeks.

[0165] Three doses of tirzepatide (5 mg, 10 mg, and 15 mg) were used in clinical trials. The efficacy and safety of escalating ipilimumab with or without metformin in adults with type 2 diabetes mellitus As an add-on to slingulargine, it demonstrated superiority from baseline compared with placebo HbA 1c Participants demonstrated a reduction in cardiovascular and weight loss across three doses of tirzepatide. Up to 97.4 percent of people have an HbA of less than 7 percent. 1c Furthermore, the most 62.4 percent of participants treated with the higher tirzepatide dose had HbA 1c was achieved.

[0166] [Table 4]

[0167] [Table 5]

[0168] HDL-C levels using the method of Example 1 are shown in FIG.

[0169] array SEQ ID NO:1 Tirzepatide YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPP P.S. X1 is Aib, X2 is Aib, and the 20th K is (2-[2-(2-A Glu)-(gammaGlu)-(gammaGlu)-CO-(CH) 18 Chemically, through conjugation of the K side chain with -CO2H to the epsilon-amino group It has been modified so that the C-terminal amino acid is amidated as a C-terminal primary amide.

Claims

1. A method for treating refractory type 2 diabetes in a patient in need thereof, comprising administering to said patient an effective amount of tirzepa. The method comprises administering to the patient once a week a medicament for treating rheumatoid arthritis, said medicament for treating rheumatoid arthritis, or a pharma- ceutically acceptable salt thereof.

2. 10. The method of claim 1, wherein the patient has had type 2 diabetes for at least 8 years.

3. The patient's HbA １ｃ The method of claim 1 or 2, wherein the goal is less than 7%.

4. The patient's HbA １ｃ The target is 5.7% or less, as described in any one of claims 1 to 3. Method of posting.

5. The patient's HbA １ｃ The method according to any one of claims 1 to 4, wherein the ratio of the saturation temperature to the saturation temperature is more than 10%. 。

6. The patient's HbA １ｃ The method according to any one of claims 1 to 4, wherein the ratio of the saturation temperature to the saturation temperature is more than 11%. 。

7. The method according to any one of claims 1 to 6, wherein the patient is at least 46 years old. Law.

8. The method according to any one of claims 1 to 7, wherein the patient is at least 60 years old. Law.

9. The patient according to any one of claims 1 to 8 is taking an SGLT2 inhibitor. method.

10. The method according to any one of claims 1 to 9, wherein the patient is taking metformin. 。

11. The method according to any one of claims 1 to 10, wherein the patient is not receiving basal insulin. Method of posting.

12. The patient was taking metformin and an SGLT2 inhibitor, but had low HbA １ｃ Goals The method according to any one of claims 1 to 11, wherein the method is not achieved.

13. The treatment with tirzepatide or a pharma- ceutically acceptable salt thereof continues for at least 40 weeks. The method according to any one of claims 1 to 12,

14. The patient is administered tirzepatide for at least 50 weeks.

3. The method according to claim 1 .

15. The patient is administered tirzepatide for at least 2 years.

13. The method according to claim 1.

16. The method of any one of claims 1 to 15, wherein the patient is non-obese.

17. The method of any one of claims 1 to 16, wherein the effective amount is 5 mg.

18. The method of any one of claims 1 to 16, wherein the effective amount is 10 mg.

19. The method of any one of claims 1 to 16, wherein the effective amount is 15 mg.

20. The method according to any one of claims 1 to 19, wherein the patient also suffers from hypertension.

21. The method according to any one of claims 1 to 20, wherein the patient is also suffering from low HDL-C. Law.

22. The method according to any one of claims 1 to 15 or 17 to 19, wherein the patient is also suffering from obesity. Method of posting.

23. The patient has at least two cardiovascular risk factors. The method according to claim 5.

24. The method according to any one of claims 1 to 19, wherein the patient has no cardiovascular risk factors. 。

25. The method according to any one of claims 1 to 24, wherein the patient has suffered from type 2 diabetes for at least 10 years. The method according to any one of claims 1 to 5.

26. A method for treating hypertension in a patient in need thereof, comprising administering to said patient an effective amount of tirzepatide or administering to said patient a pharma- ceutically acceptable salt thereof once weekly.

27. 27. The method of claim 26, wherein the patient has had type 2 diabetes for at least 8 years. 。

28. 28. The method of claim 26 or 27, wherein the patient is suffering from refractory type 2 diabetes.

29. The patient's HbA １ｃ 29. The method of claim 27 or 28, wherein the goal is less than 7%.

30. The patient's HbA １ｃ Any one of claims 26 to 29, wherein the target is 5.7% or less. The method described above.

31. The patient's HbA １ｃ is more than 10% according to any one of claims 26 to 30. method.

32. The patient's HbA １ｃ is more than 11% according to any one of claims 26 to 31. method.

33. The patient according to any one of claims 26 to 32, wherein the patient is at least 46 years old. How to.

34. The patient according to any one of claims 26 to 33, wherein the patient is at least 60 years old. How to.

35. The method according to any one of claims 26 to 34, wherein the patient is taking an SGLT2 inhibitor. Method of posting.

36. The method according to any one of claims 26 to 35, wherein the patient is taking metformin. method.

37. 37. The method according to any one of claims 26 to 36, wherein the patient is not receiving basal insulin. The method described.

38. The patient was taking metformin and an SGLT2 inhibitor, but had low HbA １ｃ Goals The method of any one of claims 26 to 37, wherein the method is not achieved.

39. The method according to any one of claims 26 to 38, wherein the treatment with tirzepatide is continued for at least 40 weeks. The method according to any one of claims 1 to 5.

40. The method of any one of claims 26 to 39, wherein the patient is also suffering from obesity.

41. The method of any one of claims 26 to 39, wherein the patient is non-obese.

42. The method of any one of claims 26 to 41, wherein the effective amount is 5 mg.

43. The method of any one of claims 26 to 41, wherein the effective amount is 10 mg.

44. The method of any one of claims 26 to 41, wherein the effective amount is 15 mg.

45. The method according to any one of claims 26 to 44, wherein the patient is also suffering from low HDL-C. method.

46. 46. ​​Any of claims 26 to 45, wherein the patient has at least two cardiovascular risk factors.

13. The method according to claim 1.

47. The method according to any one of claims 26 to 46, wherein the hypertension is a hypertensive crisis. Law.

48. The method according to any one of claims 26 to 47, wherein the method prevents a hypertensive crisis. Law.

49. The method of any one of claims 26 to 48, wherein the method prevents stroke.

50. A method for increasing HDL-C in a patient in need thereof, comprising administering to said patient an effective amount of tirzepatide. or a pharma- ceutically acceptable salt thereof to said patient once weekly.

51. 51. The method of claim 50, wherein the patient has had type 2 diabetes for at least 8 years. 。

52. 52. The method of claim 50 or 51, wherein the patient is suffering from refractory type 2 diabetes.

53. The patient according to any one of claims 50 to 52, wherein the patient is at least 46 years old. How to.

54. The patient according to any one of claims 50 to 53, wherein the patient is at least 60 years old. How to.

55. The method according to any one of claims 50 to 54, wherein the patient is taking an SGLT2 inhibitor. Method of posting.

56. The method according to any one of claims 50 to 55, wherein the patient is taking metformin. method.

57. 57. The method according to any one of claims 50 to 56, wherein the patient is not receiving basal insulin. The method described.

58. The method according to any one of claims 50 to 57, wherein the treatment with tirzepatide is continued for at least 40 weeks. The method according to any one of claims 1 to 5.

59. The method of any one of claims 50 to 58, wherein the patient is non-obese.

60. 60. The method of any one of claims 50 to 59, wherein the effective amount is 5 mg.

61. 60. The method of any one of claims 50 to 59, wherein the effective amount is 10 mg.

62. 60. The method of any one of claims 50 to 59, wherein the effective amount is 15 mg.

63. 63. Any of claims 50 to 62, wherein the patient has at least two cardiovascular risk factors.

13. The method according to claim 1.

64. The method according to any one of claims 50 to 63, wherein the patient also suffers from hypertension. 。

65. The method according to any one of claims 50 to 64, wherein the administration of tirzepatide is continued for at least 50 weeks. The method according to any one of claims 1 to 5.

66. The method according to any one of claims 50 to 65, wherein the administration of tirzepatide once a week is continued for at least two years. The method according to any one of claims 1 to 5.

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