Chilzepatide treatment method

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] This invention relates to the field of pharmaceuticals. It concerns the blood glucose levels recommended for metformin and SGLT-2 therapy. Refractory type 2 diabetes (T2 diabetes, T2 diabetes) in patients who do not reach their target values. Treatment method 2D) is provided. Patients who require an increase in HDL-C levels. A method for increasing HDL-C levels is provided. A method for lowering blood pressure in patients who need it is provided. [Brief explanation of the drawing]

[0002] [Figure 1] The graph shows the increase in HDL-C observed at week 52 using the efficacy estimand in a clinical trial conducted essentially as described in Example 1. [Figure 2] The graph shows the increase in HDL-C observed at week 40 using the efficacy estimate in a clinical trial conducted essentially as described in Example 2. [Figure 3] The graph shows the decrease in systolic blood pressure in the clinical trial described in Example 1. [Figure 4] The graph shows the reduction in diastolic blood pressure in the clinical trial described in Example 1. Detailed description of the invention

[0003] Glycated hemoglobin (HbA 1c ) is an important marker of blood glucose control in diabetes. This is considered to be the case. (American Diabetes Association (ADA) Guide) The threshold is HbA1c below 5.7%. 1c This indicates that patients with this condition are considered to have normal blood glucose levels. Yes, HbA 1cTreatment goals for patients may vary from patient to patient. However, HbA 1c persistent inadequate control contributes excessively to the onset of diabetes-related complications . Patients suffering from type 2 diabetes are often treated with the ADA treatment paradigm nevertheless, fail to achieve normoglycemia. Despite not being within the normal range , the ADA guidelines suggest that after diet, exercise, metformin, oral diabetes treatments, followed by the current treatment option of basal insulin, a reasonable HbA 1c treatment target of less than 7% is suggested. However, many patients fail to reach their HbA 1c target despite clinical treatment and are considered to have refractory type 2 diabetes.

[0004] Refractory type 2 diabetes is generally explained by (relatively stable) insulin resistance background coupled with increasingly severe insulin secretion impairment over time, or beta-cell dysfunction . Patients who have lived with type 2 diabetes for at least 8 years are more likely to have refractory type 2 diabetes. Therefore, there is a need for therapeutic methods that provide normoglycemia or near-normoglycemia in patients suffering from refractory type 2 diabetes. There is a need for therapeutic methods that provide normoglycemia or near-normoglycemia in patients suffering from refractory type 2 diabetes, wherein the patient has been treated for type 2 diabetes for at least 8 years.

[0005] Nearly half of American adults have hypertension. Hypertension is a risk factor for stroke, coronary heart disease (CHD), and other serious health threats. Type 2 diabetes Many patients who are also obese experience hypertension. However, approved for the treatment of diabetes ed treatments typically have little or no effect on the control of hypertension. Treatment options for the manage ment of hypertension are desired. Methods for treating hypertension in diabetic patients are also desired .

[0006] Low serum levels of high-density lipoprotein cholesterol (HD L-C) are 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 increase HDL-C. Longitudinal population studies have confirmed that HDL-C is inversely and independently associated with the risk of developing CHD . Pharmacotherapy that increases HDL-C levels is desired. Methods of increasing HDL-C in patients diag nosed with type 2 diabetes are desired.

[0007] The present invention provides a method of treating, preventing or delaying hypertension, comprising administering tirzepatide or a pharmaceutically acceptable salt thereof. The present invention further provides a method of treating, preventing or delaying hypertension in a patient diag nosed with type 2 diabetes, comprising administering tirzepa tide or a pharmaceutically acceptable salt thereof.

[0008] The present invention provides a method of treating, preventing or delaying low HDL-C, comprising administering tirzepatide or a pharmaceutically acceptable salt thereof. The present invention further provides a method of treating, preventing or delaying low HDL-C in a patient diagnosed with type 2 diabetes and administering tirzepatide or a pharmaceutically acceptable salt thereof, the invention provides a method .

[0009] The present invention provides a method for treating , preventing or delaying intractable type 2 diabetes in a patient who has suffered from type 2 diabetes for at least 8 years, which comprises administering tirzepatide or a pharmaceutically acceptable salt thereof , the present invention provides the method.

[0010] The present invention provides a method for treating intractable type 2 diabetes in a patient who has suffered from type 2 diabetes for at least 8 years, which comprises administering tirzepatide or a pharmaceutically acceptable salt thereof , the present invention provides the method.

[0011] In one embodiment, a patient in need of treatment for intractable type 2 diabetes has an HbA 1c of greater than 10%.

[0012] In one embodiment, a patient in need of treatment for intractable type 2 diabetes has an HbA 1c of greater than 11%.

[0013] In one embodiment, a patient in need of treatment for intractable type 2 diabetes has a treatment target of 5.7% HbA 1c . In one embodiment, a patient in need of treatment for intractable type 2 diabetes has a treatment target of 5. 7% or less HbA 1c .

[0014] In one embodiment, a patient in need of treatment for intractable type 2 diabetes has a treatment target of 6% HbA 1c treatment .

[0015] In one embodiment, a patient in need of treatment for intractable type 2 diabetes has a treatment target of 7% HbA 1c treatment .

[0016] The present invention relates to metformin, SGLT-2, or metformin + SGLT-2 inhibitors. A method for treating refractory type 2 diabetes in patients who are unresponsive, using tilzepatide or The invention provides a method comprising administering a pharmaceutically acceptable salt thereof.

[0017] Therefore, one embodiment describes a patient who needs to treat, prevent, or delay hypertension. A method for treating, preventing, or delaying hypertension, comprising an effective amount of tilzepatide or its pharmaceutical ingredients. The present invention provides a method comprising administering a suitably acceptable salt to a patient once a week. Further embodiments This is a method for treating hypertension in patients diagnosed with type 2 diabetes, comprising an effective amount of tirzepatheca The present invention provides a method comprising administering to a patient once a week a drug or a pharmaceutically acceptable salt thereof.

[0018] In another aspect, the present invention relates to a method for preventing or delaying hypertension in a patient, and is therapeutically effective. The present invention provides a method comprising administering a certain amount of tilzepatide to a patient once a week.

[0019] In another aspect, the present invention helps prevent or delay hypertension in patients diagnosed with type 2 diabetes. A method comprising administering a therapeutically effective dose of tilzepatide to a patient once a week. To provide.

[0020] In another aspect, the present invention relates to treating, preventing, or delaying the onset of hypertension in patients. The use of tilzepatide for preparing a pharmaceutical product, wherein the pharmaceutical product is administered once a week. To provide.

[0021] The present invention relates to a method for treating, preventing, or delaying hypertension, comprising an effective amount of tirzepa Administering tide or a pharmaceutically acceptable salt thereof to a patient requiring such treatment. This provides a method that includes [something].

[0022] In one embodiment, a patient requiring treatment for hypertension has type 2 diabetes, and They are not obese.

[0023] In one embodiment, a patient requiring treatment for hypertension has type 2 diabetes, and He is obese.

[0024] In one embodiment, a patient requiring treatment for hypertension suffers from refractory type 2 diabetes. .

[0025] In one embodiment, a patient requiring treatment for hypertension is treated for type 2 diabetes for at least 8 years. They are suffering from the disease.

[0026] Therefore, one embodiment describes a treatment for hypertensive crisis in patients with refractory type 2 diabetes. A method for prevention or delaying the onset of the disease, wherein an effective amount of tilzepatide or its pharmaceutically permitted The present invention provides a method comprising administering a suitable salt to a patient once a week.

[0027] In one embodiment, a patient requiring treatment for a hypertensive crisis has type 2 diabetes. They are also not obese.

[0028] In one embodiment, a patient requiring treatment for a hypertensive crisis has type 2 diabetes. He is obese.

[0029] In one embodiment, a patient requiring treatment for a hypertensive crisis suffers from refractory type 2 diabetes. They are doing it.

[0030] In one embodiment, patients requiring treatment for hypertensive crisis are treated for at least 8 years with type 2 hypertension. I have diabetes.

[0031] Therefore, one embodiment of the treatment, prevention, or delay of low HDL-C in patients A method of delaying the onset of symptoms, in which an effective amount of tilzepatide or a pharmaceutically acceptable salt thereof is administered once a week to the patient. The present invention provides a method that includes administering the substance to a person.

[0032] In another aspect, the present invention relates to a method for preventing or delaying a hypertensive crisis in a patient. This means administering an effective dose of tilzepatide or a pharmaceutically acceptable salt thereof to the patient once a week. This provides a method that includes [something].

[0033] In another aspect, the present invention relates to a method for preventing or delaying low HDL-C in patients. Therefore, administer an effective dose of tilzepatide or a pharmaceutically acceptable salt thereof to the patient once a week. Includes, provides methods.

[0034] In another embodiment, the present invention relates to oral administration over a period of at least 1, 2, 3, 4, or 5 years. For treating hypertension in patients receiving clinical treatment for type 2 diabetes with antidiabetic drugs. The law states that if the patient's HbA1c exceeds 7%, an effective dose of tilzepatide or a pharmaceutically acceptable dose is administered. The present invention provides a method comprising administering the salt to a patient once a week.

[0035] In another aspect, the present invention relates to a person suffering from type 2 diabetes mellitus. A method for improving blood glucose control in patients who are at risk of hypertension, and which contains an effective amount The treatment involves administering tilzepatide or a pharmaceutically acceptable salt thereof to the patient once a week, and the patient This provides a method that reduces the risk of experiencing a hypertensive crisis.

[0036] In another aspect, the present invention relates to a person who has type 2 diabetes mellitus and is at risk of hypertension. A method for improving blood glucose control in a patient, wherein an effective amount of tilzepatide or its pharmaceutically appropriate Treatment involves administering an acceptable salt to the patient once a week for at least 30 weeks, and the patient has hypertension. This provides a method to reduce the risk of experiencing Rize.

[0037] In another aspect, the present invention relates to weight management in patients who are obese and at risk of hypertension. A method to improve the condition, which involves administering an effective amount of tilzepatide or a pharmaceutically acceptable salt thereof once a week. This includes administering the drug to the patient multiple times, providing a reduction in the risk of the patient experiencing a hypertensive crisis. , provide a method.

[0038] In another aspect, the present invention relates to a method for treating hypertension in a patient, wherein an effective amount The treatment involves administering tilzepatide or a pharmaceutically acceptable salt thereof to the patient once a week. This method provides a way to determine if the patient's weight is within the normal weight range.

[0039] In another aspect, the present invention relates to weight management in patients who are obese and at risk of hypertension. A method to improve the condition, which involves administering an effective amount of tilzepatide or a pharmaceutically acceptable salt thereof once a week. The method, which involves administering the drug to a patient multiple times, provides a reduction in the risk of the patient experiencing hypertension. , provide a method.

[0040] In another aspect, the present invention is for treating, preventing or delaying the onset of hypertensive crisis. Chilzepatide or a pharmaceutically acceptable salt thereof for use, and the chilzepatide Or the pharmaceutically acceptable salt thereof is administered once a week, tilzepatide or the pharmaceutically acceptable salt thereof Provide salt.

[0041] In another aspect, tilzepa for use in the treatment, prevention, or delay of the onset of hypertension. Chile or a pharmaceutically acceptable salt thereof, tirzepatide or a pharmaceutically acceptable salt thereof The salt provided is tilzepatide or a pharmaceutically acceptable salt thereof, administered once a week.

[0042] In another embodiment, one embodiment describes a medical device for treating, preventing, or delaying the onset of hypertension. The use of tilzepatide or a pharmaceutically acceptable salt thereof for the preparation of pharmaceuticals, The medication is administered once a week.

[0043] In another aspect, preparing a medicine for treating, preventing, or delaying the onset of hypertension. The use of tilzepatide is provided, and the drug is administered once a week.

[0044] In another embodiment, one embodiment treats, prevents or delays the onset of a hypertensive crisis. The use of tilzepatide or a pharmaceutically acceptable salt thereof for the preparation of pharmaceuticals for the purpose of The medication is administered once a week.

[0045] In another aspect, a pharmaceutical product for treating, preventing, or delaying the onset of a hypertensive crisis. The use of tilzepatide for preparation, where the drug is administered once a week, is provided. ru.

[0046] U.S. Patent No. 9474780 describes and claims tilzepatide. When used in writing, the term "tilzepatide" refers to the amino acid sequence of SEQ ID NO: 1. This refers to any GIP / GLP-1 receptor agonist, and the party seeking approval for said protein. Has the person actually identified that protein as tilzepatide, or some other Regardless of whether the terminology is used, Eli Lilly and Company This depends on the overall or partial data on tilzepatide submitted to regulatory authorities. The regulatory submission seeking approval of GIP / GLP-1 receptor agonist products is subject to the requirements. It contains the protein. Chilzepatide acts on the GIP / GLP-1 receptor and insulin This stimulates the synthesis and secretion of glycemic agents, thereby improving blood glucose control in T2DM patients. This has been shown.

[0047] As used herein, "hypertension crisis" means a dangerously high blood pressure and a patient's condition. It means that it can threaten the body or life. A hypertensive crisis is typically at least 1 This is a blood pressure of 80 / 120. Hypertension is generally defined as a systolic / diastolic blood pressure of 130 / 80. be.

[0048] As used herein, "refractory type 2 diabetes" refers to oral standard treatment such as metformin. Using medication to increase HbA 1c This refers to patients who are unable to achieve their goals.

[0049] When used in this specification, "HbA 1c The "goal" is determined by the patient's clinical treatment plan. The desired average achieved by the patient, measured using clinically acceptable methods. HbA 1c It means level. Current ADA guidelines include diet, exercise, metformin. Following oral diabetes treatment, followed by basal insulin, the current treatment options have a success rate of less than 7%. Rational HbA 1c This suggests treatment goals. However, many patients also experience clinical treatment. Regardless of HbA 1c I was unable to reach my goal and am considered to have refractory type 2 diabetes. It can be obtained. In one embodiment, HbA 1c The target is 7% or less. In one embodiment, HbA 1c The target is 5.7% or less.

[0050] No CHD was present at baseline during the Framingham study (12-year follow-up period). Among men and women aged 49-82, participants with high HDL-C levels (80th percentile) ) compared to participants with low HDL-C levels (20th percentile), cardiovascular The risk of the event was 50 percent lower. 2 Prospective Cardiova Scular Munster (PROCAM) study (approximately 4,500 volunteers) In a study of individuals aged 16-65 years with a 6-year follow-up period, individuals with HDL-C < 35 mg / dl were Individuals with HDL-C ≥ 35 mg / dl have a four times higher risk of coronary artery disease. Assmann G et al., High-density li 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 See reference. Gordon et al. found that for every 1 mg / dl increase in HDL-C, the compound for an individual... This suggests 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 Vention Trial (VA-HIT) show that the initial stage has low HDL-C. In patients, a moderate increase of just 6 percent in HDL-C was associated with an increase in coronary artery morbidity. It showed a significant reduction of up to 24 percent in both mortality and velocity. Rubins H 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 to increase HDL-C include increased exercise and reduced dietary fat intake. This may include lifestyle improvements. In many cases, lifestyle improvements can lead to the desired increase in HDL-C. It is insufficient to achieve. Treatment options for patients requiring an increase in HDL-C are It is necessary. There is a need for therapies to treat, prevent, or delay low HDL-C.

[0052] As used herein, terms such as “treatment,” “to treat,” and “the act of treating” are used in this specification. This includes delaying or reducing the progression of a disease, condition, or disability. These terms refer to situations where a fault or condition has not actually been eliminated, and where the fault or condition Even if the progression itself is not delayed or reversed, one or more symptoms of the disorder or condition may be alleviated. This includes remission, attenuation, elimination, or reduction.

[0053] In this specification, terms such as "prevent," "preventing," and "prevention" are used as follows: This includes avoiding the onset of a disease, condition, disorder, or symptom.

[0054] As used herein, terms such as “to delay” and “to cause to delay” refer to a disease. This means including increasing the time period until the onset of a condition, disorder, or symptom.

[0055] When used herein in relation to multiple outcomes, the term “composite” refers to one of the outcomes. This refers to the occurrence of the first of any of the following:

[0056] The term "increase in HDL-C" refers to a measured HDL-C level that is higher than baseline. This means an increase. In one embodiment, the increase in HDL-C is statistically significant. It is an increase. In one embodiment, the increase in HDL-C is an increase of more than 2% from baseline. Yes. In one embodiment, the increase in HDL-C is an increase of more than 5% from baseline. In one embodiment, the increase in HDL-C is an increase of more than 7% from baseline. Morphologically, the increase in HDL-C is more than 10% from baseline.

[0057] "Therapeutic effective dose" refers to tilzepatide or its drug for the method or use of the present invention. A scientifically acceptable salt, or tilzepatide or so for the method or use of the present invention. The amount of a pharmaceutical composition containing a pharmaceutically acceptable salt of the above, which is used by researchers, physicians or other clinicians. Therefore, the desired biological or medical response of the patient or the desired therapeutic effect in the patient is sought. This refers to the amount that would induce the fruit. The amount depends on the individual's disease state, age, sex, and weight, as well as the individual's ability to elicit a desired response. The effective dose may vary depending on factors such as the capacity of tilzepatide. However, the amount is greater than the amount that would cause toxicity or adverse effects. In certain embodiments, the method described herein The therapeutically effective dose of tilzepatide or its pharmaceutically acceptable salt for use is 5, 10 The group is selected from the group consisting of and 15 mg. In a particular embodiment, tilzepatide or the drug The scientifically acceptable therapeutic dose of salt is 5.0 mg. In certain embodiments, tilzepa The therapeutically effective dose of tide or its pharmaceutically acceptable salt is 10.0 mg. Specific implementation In this state, the therapeutically effective dose of tilzepatide or its pharmaceutically acceptable salt is 15.0 mg. ru.

[0058] Additional embodiments are described below.

[0059] In one embodiment, blood glucose control is improved in patients with type 2 diabetes mellitus, and HDL-C A method for increasing the amount of tilzepatide or a pharmaceutically acceptable salt thereof in a therapeutically effective dose. A method comprising administering the medication to the patient once a week for at least 30 weeks.

[0060] In one embodiment, tilzepatide or a pharmaceutically acceptable salt thereof is administered for at least 40 weeks. It is administered. In one embodiment, tilzepatide or a pharmaceutically acceptable salt thereof is administered at least It is administered for 52 weeks.

[0061] Hypertension and normal HbA1c 1c blood sugar A method for treating, preventing, or delaying the onset of hypertension in a patient, wherein the therapeutically effective amount A method comprising administering to the patient once a week tilzepatide or a pharmaceutically acceptable salt thereof. In one embodiment, hypertension is selected from the group consisting of hypertension and hypertensive crisis.

[0062] A method for preventing or delaying hypertension in a patient, comprising a therapeutically effective dose of tilzepatide or A method comprising administering a pharmaceutically acceptable salt of the salt to the patient once a week.

[0063] To improve blood glucose control in patients diagnosed with type 2 diabetes mellitus, and to treat and prolong hypertension in these patients. A method for preventing or delaying the onset of tilzepatide in a therapeutically effective dose or a pharmaceutically acceptable dose thereof. A method comprising administering salt to a patient once a week.

[0064] In one embodiment, the method reduces the risk of a patient experiencing hypertension. In this embodiment, the risk of the patient experiencing a hypertensive crisis is reduced by the method. Therefore, this method reduces the risk of patients experiencing clinically low HDL-C levels.

[0065] A method for improving blood glucose control in patients with type 2 diabetes mellitus, and which has therapeutic properties. The treatment includes administering an effective dose of tilzepatide or a pharmaceutically acceptable salt thereof to the patient once a week. A method that reduces the risk of patients experiencing hypertension.

[0066] The patient has type 2 diabetes mellitus, according to any of the embodiments described above. The method according to any of the above embodiments, wherein the patient has refractory type 2 diabetes. The method according to any of the above embodiments, wherein the patient has had a urinary tract disease for at least 8 years. The method according to any of the above embodiments, wherein the person has had type 1 diabetes for at least 10 years. A single dose of tilzepatide is continued for at least 40 weeks, as described in any of the embodiments above. The method described above. The patient is not obese, and the method is described in any of the embodiments above.

[0067] The patient has one or more of the following conditions: T2DM, hypertension, decreased HDL-C, and obesity. The method according to any of the embodiments described above.

[0068] In one embodiment, the patient has multiple cardiovascular risk factors without hypertension, or clinically significant They have one of the following conditions: high blood pressure.

[0069] In one embodiment, the patient has multiple cardiovascular risk factors or an HbA1c level greater than 11%. It has one of the following characteristics:

[0070] As used herein, “cardiovascular risk factors” means current tobacco use (any form of tobacco use) Smoking); within the past 6 months, at least one treatment for hypercholesterolemia Use of approved lipid modifying therapies, or reported untreated Low-density lipoprotein cholesterol (LDL) -C)≧3.4 mmol / L (100 mg / dL); Reported treatment within the past 6 months For men who have received treatment or have not received treatment, the level should be less than 1.0 mmol / L (40 mg / dL), and For women, high-density lipoprotein (DPP) levels less than 1.3 mmol / L (50 mg / dL) Resterol (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 pressure Systolic blood pressure (SBP) ≥ 130 mmHg or diastolic blood pressure (DIA) Stolic blood pressure (DBP) ≥ 80 mmHg; for men, 102 cm; for women. Therefore, the risk of cardiovascular disease is selected from the group consisting of a measured lumbar circumference of 88 cm; It means...

[0071] As used herein, "non-obese" refers to a patient who is not obese by applicable criteria. This means that, in one embodiment, a non-obese patient has an obesity index of less than 30 BMI.

[0072] As used herein, "concurrent" means that a patient has two or more medical conditions. This means being diagnosed with [that condition].

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

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

[0075] In one embodiment, the HDL-C level is increased. This is increased to a clinically desirable level. In one embodiment, a patient suffering from type 2 diabetes mellitus... A method to improve blood glucose control in patients and increase HDL-C, using tilzepatide or The patient is given a pharmaceutically acceptable salt of the drug at a therapeutically effective dose once a week for at least 30 weeks. This is a method that includes the following.

[0076] In one embodiment, the risk 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 an effective dose of tilzepatide or It is reduced in patients treated with a pharmaceutically acceptable salt.

[0078] In one embodiment, the risk of developing both hypertension and HbA1c above 5.7% is reduced. In this embodiment, the risk of co-occurring low HDL-C, hypertension, and HbA1c greater than 7% is reduced. ru.

[0079] In one embodiment, the risk of co-occurring low HDL-C, hypertension, and HbA1c > 5.7% is: It will be reduced.

[0080] In one embodiment, the risk of co-occurring low HDL-C, hypertension, and HbA1c > 6% is reduced. It will be done.

[0081] A method to normalize HbA1c blood glucose levels in patients with refractory type 2 diabetes. This involves administering a therapeutically effective dose of tilzepatide or a pharmaceutically acceptable salt thereof to the patient once a week. A method that includes doing so.

[0082] In one embodiment, the amounts of tilzepatide are approximately 5.0 mg, approximately 10.0 mg, and approximately 15.0 mg. Selected from the group consisting of mg. In one embodiment, the amount of tilzepatide is approximately 7.5 mg and The group is selected from a selection consisting of approximately 12.5 mg.

[0083] In one embodiment, the amount of tilzepatide is approximately 5.0 mg.

[0084] In one embodiment, the amount of tilzepatide is approximately 10.0 mg.

[0085] In one embodiment, the amount of tilzepatide is approximately 15.0 mg.

[0086] In one embodiment, the dose of tilzepatide is approximately 5.0 mg.

[0087] In one embodiment, the dose of tilzepatide is approximately 10.0 mg.

[0088] In one embodiment, the dose of tilzepatide is approximately 15.0 mg.

[0089] In one embodiment, tilzepatide or a pharmaceutically acceptable salt thereof is used in a dose escalation protocol. It is administered using [a specific method / tool].

[0090] In one embodiment, the patient is treated with tilzepatide or a pharmaceutically acceptable salt thereof. Prior to this, even after using one or two oral diabetes medications for at least one year, HbA1c < 7 The percentage cannot be achieved.

[0091] In one embodiment, the patient is treated with tilzepatide or a pharmaceutically acceptable salt thereof. Before that, even after using one or two oral medications for at least one year, achieving an HbA1c < 8% It cannot be done.

[0092] In one embodiment, the patient is treated with tilzepatide or a pharmaceutically acceptable salt thereof. Prior to this, even after using one or two oral medications for at least one year, HbA1c < 10% It cannot be achieved.

[0093] In one embodiment, once-weekly administration of tilzepatide or a pharmaceutically acceptable salt thereof is less than It is continued for at least 30 weeks. In one embodiment, tilzepatide or a pharmaceutically acceptable thereof The weekly administration of salt is continued for at least 40 weeks. In one embodiment, tilzepatide or The weekly administration of the pharmaceutically acceptable salt is continued for at least 50 weeks. In terms of form, once-weekly administration of tilzepatide or a pharmaceutically acceptable salt thereof is at least 2 This is continued for a year. In one embodiment, tilzepatide or a pharmaceutically acceptable salt thereof is administered once a week. The administration of the drug is continued for at least 3 years. In one embodiment, tilzepatide or its pharmaceutical The once-weekly administration of the acceptable salt is to be continued for at least 5 years.

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

[0095] In one embodiment, the patient was diagnosed with type 2 diabetes due to tilzepatide or its pharmaceutically beneficial properties. The administration of acceptable salt was at least eight years prior.

[0096] In one embodiment, patients administered tilzepatide or a pharmaceutically acceptable salt thereof are type 2. The patient was diagnosed with diabetes at least 10 years prior to being administered tilzepatide.

[0097] In one embodiment, patients administered tilzepatide or a pharmaceutically acceptable salt thereof are type 2. The patient was diagnosed with diabetes at least 13 years prior to being administered tilzepatide.

[0098] In one embodiment, patients administered tilzepatide or a pharmaceutically acceptable salt thereof are less likely to be affected. At the very least, he is 46 years old.

[0099] In one embodiment, patients administered tilzepatide or a pharmaceutically acceptable salt thereof are less likely to be affected. At the very least, he is 55 years old.

[0100] In one embodiment, patients administered tilzepatide or a pharmaceutically acceptable salt thereof are less likely to be affected. At the very least, he is 60 years old.

[0101] In one embodiment, patients administered tilzepatide or a pharmaceutically acceptable salt thereof are Toformin and oral SGLT2 medications are also administered.

[0102] In one embodiment, a patient administered tilzepatide or a pharmaceutically acceptable salt thereof is S Oral GLT2 medication is also administered.

[0103] In one embodiment, patients administered tilzepatide or a pharmaceutically acceptable salt thereof are Toformin is also administered.

[0104] In one embodiment, patients administered tilzepatide or a pharmaceutically acceptable salt thereof are based Corneal insulin is also administered.

[0105] In one embodiment, patients administered tilzepatide or a pharmaceutically acceptable salt thereof are Toformin and basal insulin are also administered.

[0106] In one embodiment, a patient administered tilzepatide or a pharmaceutically acceptable salt thereof is S GLT2 and basal insulin are also administered.

[0107] In one embodiment, patients administered tilzepatide or a pharmaceutically acceptable salt thereof are Toformin, SGLT2 inhibitors, 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, a patient administered tilzepatide or a pharmaceutically acceptable salt thereof is S Oral GLT2 medications are also administered.

[0111] In one embodiment, patients administered tilzepatide or a pharmaceutically acceptable salt thereof are Toformin, oral SGLT2, and insulin degludec are also administered.

[0112] In one embodiment, patients administered tilzepatide or a pharmaceutically acceptable salt thereof are Toformin, oral SGLT2, and insulin degludec are also administered.

[0113] In one embodiment, patients administered tilzepatide or a pharmaceutically acceptable salt thereof are Toformin, oral SGLT2, and insulin glargine are also administered.

[0114] In one embodiment, patients administered tilzepatide or a pharmaceutically acceptable salt thereof are Toformin and insulin glargine are also administered.

[0115] Chilzepatide or a pharmaceutically acceptable salt thereof for use in any of the above embodiments. .

[0116] Chilzepatide or the drug in the preparation of a pharmaceutical for any of the embodiments described above The use of scientifically acceptable salts.

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

[0118] One embodiment is for use in treating, preventing, or delaying hypertension in patients. Chilzepatide or a pharmaceutically acceptable salt thereof, which is chilzepatide or a pharmaceutically acceptable salt thereof The acceptable salt is administered once a week and provides tilzepatide or a pharmaceutically acceptable salt thereof. Further embodiments include a chill for treating hypertension in patients diagnosed with type 2 diabetes. Zepatide or a pharmaceutically acceptable salt thereof, which is tylzepatide or a pharmaceutically acceptable salt thereof The salt provided is tilzepatide or a pharmaceutically acceptable salt thereof, administered once a week.

[0119] In another embodiment, the present invention is used to prevent or delay hypertension in patients. Chilzepatide or its pharmaceutically acceptable salt, for use with chilzepatide or its pharmaceutically acceptable salt A pharmaceutically acceptable salt is administered once a week, either tilzepatide or a pharmaceutically acceptable salt thereof. Provided. In one embodiment, the patient is diagnosed with type 2 diabetes. In a further embodiment, The patient has type 2 diabetes and is not obese. In another embodiment, the patient is 2 The patient has type 2 diabetes and is obese. In a further embodiment, the patient has refractory type 2 diabetes. The patient suffers from a urinary tract disease. In another further embodiment, the patient has had type 2 diabetes for at least 8 years. He is suffering from [the disease].

[0120] In another embodiment, the present invention treats, prevents, or delays the onset of a patient's hypertensive crisis. Chilzepatide or a pharmaceutically acceptable salt thereof for use in causing, Patide or a pharmaceutically acceptable salt thereof is administered once a week, tilzepatide or its pharmaceutically acceptable salt Provides a salt that is acceptable. In one embodiment, the patient is diagnosed with type 2 diabetes. In one embodiment, the patient has type 2 diabetes and is not obese. Another embodiment In this state, the patient has type 2 diabetes and is obese. In a further embodiment, the patient The person has refractory type 2 diabetes. In another further embodiment, the patient has at least I have had type 2 diabetes for eight years.

[0121] In another embodiment, the present invention treats, prevents, or delays the onset of low HDL-C in patients. Chilzepatide or a pharmaceutically acceptable salt thereof for use in the treatment of Chilzepatide or a pharmaceutically acceptable salt thereof is administered once a week, Chilzepatide or a pharmaceutically acceptable salt thereof Provide an acceptable amount of salt.

[0122] In another embodiment, the present invention prevents or delays the onset of low HDL-C in patients. Chilzepatide or a pharmaceutically acceptable salt thereof for use in, and The pharmaceutically acceptable salt is administered once a week, tilzepatide or its pharmaceutically acceptable Provide salt.

[0123] In another embodiment, the present invention provides oral antimicrobial protection for at least one, two, three, four, or five years. For use in the treatment of hypertension in patients receiving clinical treatment for type 2 diabetes with diabetes medications. For tylzepatide or a pharmaceutically acceptable salt thereof, where the patient's HbA1c is greater than 7% Yes, tilzepatide or a pharmaceutically acceptable salt thereof is administered once a week, tilzepatide or It provides a pharmaceutically acceptable salt thereof.

[0124] In another embodiment, the present invention relates to a person who has type 2 diabetes mellitus and is at risk of hypertension. Tilzepatide or its pharmaceutically appropriate use for improving blood glucose control in a patient The acceptable salt, tilzepatide or a pharmaceutically acceptable salt thereof, is administered once a week. The present invention provides tirzepatide or a pharmaceutically acceptable salt thereof. In one embodiment, tirzepatide D or a pharmaceutically acceptable salt thereof is administered once a week for at least 30 weeks.

[0125] In another embodiment, the present invention relates to the body of a patient who is obese and at risk of hypertension. Chilzepatide or its pharmaceutically acceptable salts for use in improving severe management Therefore, tilzepatide or a pharmaceutically acceptable salt thereof is administered once a week, tilzepatide or Provide the pharmaceutically acceptable salt thereof.

[0126] In another embodiment, the present invention relates to a tilzepaci for use in treating hypertension in patients. d or a pharmaceutically acceptable salt thereof, tilzepatide or a pharmaceutically acceptable salt thereof It is administered once a week, and the patient's weight is within the normal range for the patient, tilzepatide Or, to provide a pharmaceutically acceptable salt thereof. In other embodiments, the present invention provides the following: ru.

[0127] Embodiment 1. Tilzepatide or for use in the treatment of refractory type 2 diabetes in patients is a pharmaceutically acceptable salt thereof, and the tilzepatide or its pharmaceutically acceptable salt This is administered once a week and consists of tilzepatide or a pharmaceutically acceptable salt thereof.

[0128] Embodiment 2. Tilzepatide or its pharmaceuticals for use in the treatment of hypertension in patients A pharmaceutically acceptable salt, said tilzepatide or its pharmaceutically acceptable salt, is administered once a week. Chilzepatide or a pharmaceutically acceptable salt thereof, to be administered.

[0129] Embodiment 3. Chilzepatide for use in increasing HDL-C in patients or a pharmaceutically acceptable salt thereof, wherein the tilzepatide or its pharmaceutically acceptable The salt administered once a week is tilzepatide or a pharmaceutically acceptable salt thereof.

[0130] Embodiment 4. The patient has had type 2 diabetes for at least 8 years, Embodiment 1~ Chilzepatide or a pharmaceutically acceptable salt thereof for use as described in any one of 3.

[0131] Embodiment 5. The patient's HbA 1c The target is less than 7%, in any of Embodiments 1-4. Chilzepatide or a pharmaceutically acceptable salt thereof for use as described in one.

[0132] Embodiment 6. The patient's HbA 1c The target is 5.7% or less, in any of the embodiments 1 to 5. Chilzepatide or any pharmaceutically acceptable salt thereof for use as described in any one of the following.

[0133] Embodiment 7. The patient's HbA 1c is more than 10%, any one of embodiments 1 to 6 Chilzepatide or a pharmaceutically acceptable salt thereof for use as described above.

[0134] Embodiment 8. The patient's HbA 1c is more than 11%, any one of Embodiments 1 to 7 Chilzepatide or a pharmaceutically acceptable salt thereof for use as described above.

[0135] Embodiment 9. The patient's age is at least 46 years, one of Embodiments 1 to 8 Tilzepatide or a pharmaceutically acceptable salt thereof for use as described above.

[0136] Embodiment 10. The patient is at least 60 years old, one of Embodiments 1 to 9. Chilzepatide or a pharmaceutically acceptable salt thereof for use as described in one.

[0137] Embodiment 11. The patient is taking an SGLT2 inhibitor, one of Embodiments 1 to 10 Chilzepatide or any pharmaceutically acceptable salt thereof for use as described in any one of the following.

[0138] Embodiment 12. The patient is taking metformin, one of Embodiments 1 to 11. Chilzepatide or a pharmaceutically acceptable salt thereof for use as described in one.

[0139] Embodiment 13. The patient has not been administered basal insulin, as in Embodiments 1-12. Chilzepatide or any pharmaceutically acceptable salt thereof for use as described in any one of the following.

[0140] Embodiment 14. The patient is taking metformin and an SGLT2 inhibitor, H bA 1c For use described in any one of embodiments 1 to 13, the objective has not been achieved. Chilzepatide or a pharmaceutically acceptable salt thereof.

[0141] Embodiment 15. The tilzepatide or its pharmaceutically acceptable salt is administered for at least 40 weeks. Chilzepatide or for use as described in any one of Embodiments 1 to 14, administered intermittently. The pharmaceutically acceptable salt.

[0142] Embodiment 16. The tilzepatide or its pharmaceutically acceptable salt is administered for at least 50 weeks. Chilzepatide or for use as described in any one of Embodiments 1 to 15, administered intermittently. The pharmaceutically acceptable salt.

[0143] Embodiment 17. The tilzepatide or a pharmaceutically acceptable salt thereof is used for at least two years. Chilzepatide or so for use as described in any one of Embodiments 1 to 16 is administered. A pharmaceutically acceptable salt of [the substance].

[0144] Embodiment 18. The patient is not obese, and the use described in any one of Embodiments 1 to 17 Chilzepatide or its pharmaceutically acceptable salts for use.

[0145] Embodiment 19. The once-weekly dose of tilzepatide or its pharmaceutically acceptable salt is 5 m g is tilzepatide or the use described in any one of Embodiments 1 to 18. Pharmaceutically acceptable salts.

[0146] Embodiment 20. The once-weekly dose of tilzepatide or its pharmaceutically acceptable salt is 10 mg of tilzepatide or so for use as described in any one of Embodiments 1 to 18 A pharmaceutically acceptable salt of [the substance].

[0147] Embodiment 21. The once-weekly dose of tilzepatide or a pharmaceutically acceptable salt thereof is 15 mg of tilzepatide or so for use as described in any one of Embodiments 1 to 18 A pharmaceutically acceptable salt of [the substance].

[0148] Embodiment 22. The patient has concomitant hypertension, one of the embodiments 1 to 21. Tilzepatide or a pharmaceutically acceptable salt thereof for use as described above.

[0149] Embodiment 23. The patient has concomitant low HDL-C, and is one of any of Embodiments 1 to 22. or tylzepatide or a pharmaceutically acceptable salt thereof for use as described in one of the following.

[0150] Embodiment 24. The patient is obese, as described in Embodiments 1-17 or 19-22. Chilzepatide or a pharmaceutically acceptable salt thereof for use as described in any one of the following.

[0151] Embodiment 25. The patient has at least two cardiovascular risk factors, Embodiment 1~ Chilzepatide or a pharmaceutically acceptable salt thereof for use as described in any one of 21.

[0152] Embodiment 26. The patient does not have any cardiovascular risk factors, as described in any of Embodiments 1 to 21. Chilzepatide or a pharmaceutically acceptable salt thereof for use as described in one.

[0153] Embodiment 27. The patient has had type 2 diabetes for at least 10 years, Tilzepatide or its pharmaceutically acceptable use as described in any one of states 1 to 26 Salt.

[0154] As used herein, “estimated” means a requirement arising from the requirements of a particular regulatory body. This refers to the efficacy and treatment regimen that are evaluated to determine the effectiveness of tilzepatide. Use the efficacy Estimand before discontinuing the study drug, or for persistent severe hyperglycemia. Evaluate outcomes in humans before initiating salvage therapy. Treatment regimen estimate - Required by certain regulatory authorities, including the U.S. Food and Drug Administration, is the abolition of tilzepatide. Regardless of whether a healer or rescue therapy is initiated for persistent severe hyperglycemia, in the trial Evaluate the therapeutic effect on the human body. [Examples]

[0155] Example 1. Clinical trial using tilzepatide The registration criteria listed in Table 1 below are similar to those seen in patients with typical diabetes. The participants included some patients with type 2 diabetes who were refractory to oral treatment. is designed to include. Elderly patients are included. The average duration of type 2 diabetes is about 8 years . The trial will continue for 52 weeks.

[0156]

Table 1

[0157] The trial consists of a single-masked 3-week placebo run-in period following a screening visit is designed as such. Thereafter, patients are randomized to tirzepatide 5, 10 or 15 mg (titrated administered using a dose protocol) or insulin degludec (standard titration protocol) and followed up at approximately 1-month intervals. Patients receiving insulin degludec follow a standard insulin degludec titration protocol during the trial. The trial protocol includes standard blood pressure measurement at each visit using standard clinical methods, and serum lipid profiling at baseline and at week 52 including lipid profile. Blood pressure measurements obtained using the method of Example 1 are shown in Figure 3 and Figure 4. Actual HDL-C levels obtained using the method of Example 1 are shown in Figure 1.

[0158] Up to 92.6 percent of participants who received tirzepatide treatment achieved an HbA of less than 7 percent, which is the target value recommended by the American Diabetes Association for patients with diabetes 1c . In the trial Up to 48.5 percent of participants who received tirzepatide achieved an H bA 1c - the level seen in non-diabetic humans - was achieved.

[0159]

Table 2

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

[0161] Example 2. Clinical trial using tilzepatide The registration criteria shown in Table 3 below apply to patients who are considered refractory to oral treatment for type 2 diabetes. This includes the patient. However, oral diabetes treatment will continue throughout the trial. Average type 2 diabetes The duration of effect is approximately 13 years. The trial will last for 40 weeks.

[0162] Clinical Trial 2, Table 3

[0163] [Table 3]

[0164] The trial is designed to consist of a screening visit followed by a three-week introductory period. Subsequently, the patient received treatment with insulin glargine, either in combination with or without metformin. As an addition to the treatment, tilzepatide 5, 10, or 15 mg or placebo 40 A weekly randomized, double-blind trial will be initiated. The dose of insulin glargine will be validated. Uses a "treat-to-target algorithm". The entire test was then titrated. Patients were treated at approximately one-week intervals, and then for approximately one month. Patients will be tracked at intervals. The study protocol involves measuring blood pressure at each visit using standard clinical methods. This includes serum lipid profiles at the start of the study and at 40 weeks.

[0165] The three doses of tilzepatide (5 mg, 10 mg, and 15 mg) are based on the clinical trial dose. In adults with type 2 diabetes, the gradual increase in metformin with or without metformin When added to insulin glargine, it demonstrated superior reduction in HbA 1c 1c and body weight from baseline compared with placebo. Across the three tirzepatide doses, up to 97.4% of participants achieved an HbA 1c of less than 7%. Furthermore, 62.4% of participants treated with the highest tirzepatide dose achieved an HbA 1c 1c of less than 5.7%. 1c 1c

[0166] [Table 4]

[0167] [Table 5]

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

[0169] Sequence SEQ ID NO: 1 tirzepatide YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS X1 is Aib, X2 is Aib, the K at position 20 is chemically modified through conjugation to the epsilon-amino group of the K side chain with (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)1-CO-(CH2) 18 -CO2H, and the C-terminal amino acid is amidated as a C-terminal primary amide. The invention described in the original claims of this application is listed below. [1] A method for treating refractory type 2 diabetes in a patient in need, comprising administering an effective amount of tilzepatide or a pharmaceutically acceptable salt thereof to the patient once weekly. [2] The patient has had type 2 diabetes for at least 8 years, the method described in [1]. [3] The aforementioned patient had HbA 1c The target is less than 7%, as described in [1] or [2]. [4] The patient with HbA ​​1c The target is 5.7% or less, by any of the methods described in [1] to [3]. [5] The patient with HbA 1c This is a method of any of [1] to [4], which is more than 10%. [6] The patient in question has HbA 1c This is more than 11% and is one of the methods described in [1] to [4]. [7] The patient's age is at least 46 years, as described in any of [1] to [6]. [8] The patient's age is at least 60 years, as described in any of [1] to [7]. [9] The patient is taking an SGLT2 inhibitor, as described in any of [1] to [8].

[10] The patient is taking metformin, according to any of the methods in [1] to [9].

[11] The patient is not receiving basal insulin. The method according to any one of [1] to

[10] .

[12] The patient is taking metformin and an SGLT2 inhibitor, but HbA 1c Any method [1] through

[11] that fails to achieve the goal.

[13] Treatment with tilzepatide or a pharmaceutically acceptable salt thereof, the method according to any one of [1] to

[12] , wherein treatment is continued for at least 40 weeks.

[14] The patient is administered tilzepatide for at least 50 weeks, according to any of the methods in [1] to

[13] .

[15] The patient is administered tilzepatide for at least two years, according to any of the methods in [1] to

[14] .

[16] The patient is not obese, and the method is one of the methods in [1] to

[15] .

[17] The effective dose is 5 mg, according to any of the methods in [1] to

[16] .

[18] The effective dose is 10 mg, according to any of the methods in [1] to

[16] .

[19] The effective dose is 15 mg, according to any of the methods in [1] to

[16] .

[20] The patient has concomitant hypertension, the method according to any of [1] to

[19] .

[21] The patient has concomitant low HDL-C, and the method is described in any of [1] to

[20] .

[22] The patient is also obese, the method according to any of [1]-

[15] or

[17] -

[19] .

[23] The patient having at least two cardiovascular risk factors, the method according to any one of [1] to

[22] .

[24] The patient has no cardiovascular risk factors, and the method according to any one of [1] to

[19] .

[25] The patient has had type 2 diabetes for at least 10 years, by any of the methods described in [1] to

[24] .

[26] A method for treating hypertension in a patient in need, comprising administering to the patient an effective amount of tilzepatide or a pharmaceutically acceptable salt thereof once weekly.

[27] The patient has had type 2 diabetes for at least 8 years, the method described in

[26] .

[28] The patient has refractory type 2 diabetes, the method according to

[26] or

[27] .

[29] HbA of the aforementioned patient 1c The target is less than 7%, as described in

[27] or

[28] .

[30] The patient with HbA 1c The target is 5.7% or less, by any of the methods described in

[26] –

[29] .

[31] The HbA of the aforementioned patient 1c This is the method described in any of

[26] to

[30] , which is more than 10%.

[32] HbA of the aforementioned patient 1c The method described in any of

[26] to

[31] is more than 11%.

[33] The patient's age is at least 46 years, as described in any of

[26] to

[32] .

[34] The patient's age is at least 60 years, as described in any of

[26] to

[33] .

[35] The patient is taking an SGLT2 inhibitor, as described in any of

[26] to

[34] .

[36] The patient is taking metformin, as described in any of

[26] to

[35] .

[37] The patient is not administered basal insulin. The method according to any one of

[26] to

[36] .

[38] The patient is taking metformin and an SGLT2 inhibitor, but HbA 1c Any method described in

[26] to

[37] that fails to achieve the goal.

[39] Treatment with tilzepatide as described above, continued for at least 40 weeks, as described in any of

[26] -

[38] .

[40] The patient is also obese, by any of the methods in

[26] to

[39] .

[41] The patient is not obese, by any of the methods in

[26] to

[39] .

[42] The effective dose is 5 mg, according to any one of

[26] to

[41] .

[43] The effective dose is 10 mg, according to any of the methods in

[26] to

[41] .

[44] The effective dose is 15 mg, according to any of the methods in

[26] to

[41] .

[45] The patient has concomitant low HDL-C, as described in any of

[26] to

[44] .

[46] The patient has at least two cardiovascular risk factors, as described in any of

[26] to

[45] .

[47] The hypertension is a hypertensive crisis, as described in any of

[26] to

[46] .

[48] ​​The method described above is any of the methods described in

[26] to

[47] for preventing a hypertensive crisis.

[49] The method described above is any of the methods described in

[26] to

[48] for preventing stroke.

[50] A method for increasing HDL-C in a patient in need, comprising administering an effective amount of tilzepatide or a pharmaceutically acceptable salt thereof to the patient once weekly.

[51] The patient has had type 2 diabetes for at least eight years, the method described in

[50] .

[52] The patient has refractory type 2 diabetes, the method according to

[50] or

[51] .

[53] The patient's age is at least 46 years, as described in any of

[50] to

[52] .

[54] The patient's age is at least 60 years, as described in any of

[50] to

[53] .

[55] The patient is taking an SGLT2 inhibitor, according to any of the methods in

[50] to

[54] .

[56] The patient is taking metformin, according to any of the methods in

[50] to

[55] .

[57] The patient is not receiving basal insulin. The method of any one of

[50] to

[56] .

[58] Treatment with tilzepatide as described above, continued for at least 40 weeks, as described in any of

[50] -

[57] .

[59] The patient is not obese, by any of the methods in

[50] to

[58] .

[60] The effective dose is 5 mg, according to any of the methods in

[50] to

[59] .

[61] The effective dose is 10 mg, according to any of the methods in

[50] to

[59] .

[62] The effective dose is 15 mg, according to any of the methods in

[50] to

[59] .

[63] The patient having at least two cardiovascular risk factors, the method according to any one of

[50] to

[62] .

[64] The patient has concomitant hypertension, the method according to any of

[50] to

[63] .

[65] The method according to any one of

[50] to

[64] , wherein the administration of tilzepatide is continued for at least 50 weeks.

[66] The method described in any of

[50] –

[65] , in which once-weekly administration of tilzepatide is continued for at least two years.

Claims

1. A pharmaceutical composition for treating hypertension in patients in need, comprising an effective amount of tilzepatide or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition is administered to the patient once a week. The aforementioned patient suffers from type 2 diabetes. Pharmaceutical composition.

2. The pharmaceutical composition according to claim 1, wherein the patient has been suffering from type 2 diabetes for at least eight years.

3. The pharmaceutical composition according to claim 1 or 2, wherein the patient suffers from refractory type 2 diabetes.

4. The HbA of the aforementioned patient １ｃ The target is less than 7%, the pharmaceutical composition according to claim 2 or 3.

5. The HbA of the aforementioned patient １ｃ The target is a pharmaceutical composition according to any one of claims 1 to 4, wherein the content is 5.7% or less.

6. The HbA of the aforementioned patient １ｃ The pharmaceutical composition according to any one of claims 1 to 5, wherein the amount is more than 10%.

7. The HbA of the aforementioned patient １ｃ The pharmaceutical composition according to any one of claims 1 to 6, wherein the amount is more than 11%.

8. The pharmaceutical composition according to any one of claims 1 to 7, wherein the age of the patient is at least 46 years.

9. The pharmaceutical composition according to any one of claims 1 to 8, wherein the age of the patient is at least 60 years.

10. The pharmaceutical composition according to any one of claims 1 to 9, wherein the patient is taking an SGLT2 inhibitor.

11. The pharmaceutical composition according to any one of claims 1 to 10, wherein the patient is taking metformin.

12. The pharmaceutical composition according to any one of claims 1 to 11, wherein the patient has not been administered basal insulin.

13. The aforementioned patient is taking metformin and SGLT2 inhibitors, but HbA １ｃ A pharmaceutical composition according to any one of claims 1 to 12 that does not achieve the objective.

14. The pharmaceutical composition according to any one of claims 1 to 13, wherein the treatment with tilzepatide is continued for at least 40 weeks.

15. The pharmaceutical composition according to any one of claims 1 to 14, wherein the patient also suffers from obesity.

16. The pharmaceutical composition according to any one of claims 1 to 14, wherein the patient is not obese.

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

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

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

20. The pharmaceutical composition according to any one of claims 1 to 19, wherein the patient also has low HDL-C.

21. The pharmaceutical composition according to any one of claims 1 to 20, wherein the patient has at least two cardiovascular risk factors.

22. The pharmaceutical composition according to any one of claims 1 to 21, wherein the hypertension is a hypertensive crisis.

23. The pharmaceutical composition is the pharmaceutical composition according to any one of claims 1 to 22, which prevents hypertensive crisis.

24. The pharmaceutical composition is the pharmaceutical composition according to any one of claims 1 to 23, which prevents stroke.

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