Efficacy and Safety of Tirzepatide for Weight Management

Inclusion Criteria Common inclusion criteria for both diabetic and non-diabetic individuals: * Informed consent will be obtained before any trial-related activities. * Male or female, aged ≥18 years at the time of signing the informed consent form. * Have a history of at least one self-reported unsuccessful dietary effort to lose body weight. * Body mass index (BMI): * ≥30 kg/m² with or without any weight-related comorbidities or * ≥25-29.9 kg/m² with the presence of at least one of the following weight-related comorbidities (treated or untreated): * Hypertension (systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg or currently taking antihypertensive medication). * Dyslipidemia (treated or with low-density lipoprotein (LDL) ≥160 mg/dL (4.1 mmol/L) or triglycerides ≥150 mg/dL (1.7 mmol/L), or high-density lipoprotein (HDL) \<40 mg/dL (1.0 mmol/L) for men or HDL \<50 mg/dL (1.3 mmol/L) for women). * Obstructive sleep apnea. * Cardiovascular disease (more than three months). * In the investigator's opinion, are well-motivated, capable, and willing to: * Learn how to self-inject study drug, as required for this protocol (visually impaired persons who are not able to perform the injections must have the assistance of a sighted individual trained to inject study drug; persons with physical limitations who are not able to perform the injections must have the assistance of an individual trained to inject study drug). * Inject study drug (or receive an injection from a trained individual if visually impaired or with physical limitations). * Follow study procedures for the duration of the study, including, but not limited to, following lifestyle advice (for example, dietary restrictions and exercise plan) and maintaining a study diary. * Male participants: * Male participants with partners of childbearing potential should be willing to use reliable contraceptive methods throughout the study and for 5 half-lives of the study drug plus 90 days, corresponding to 4 months after the last injection. * Female participants: * Female participants not of childbearing potential may participate and include those who are: * Infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as Mullerian agenesis. * Postmenopausal, defined as either: * A woman at least 40 years of age with an intact uterus, not on hormone therapy, who has cessation of menses for at least 1 year without an alternative medical cause, AND a follicle-stimulating hormone ≥40 mIU/mL; women in this category must test negative in pregnancy test prior to study entry. * A woman 55 or older not on hormone therapy, who has had at least 12 months of spontaneous amenorrhea. * A woman at least 55 years of age with a diagnosis of menopause prior to starting hormone replacement therapy. * Female participants of childbearing potential (not surgically sterilized and between menarche and 1-year postmenopausal) must: * Test negative for pregnancy at Visit 1 based on a serum pregnancy test. * If sexually active, agree to use 2 forms of effective contraception, where at least 1 form is highly effective, for the duration of the trial and for 30 days thereafter. * Not be breastfeeding. For subjects with T2DM: * Patients diagnosed with T2DM more than or equal to 180 days prior to the day of screening. * HbA1c up to 10.0%. Exclusion Criteria Common exclusion criteria for both diabetic and non-diabetic individuals: * Medical criteria: * Have obesity induced by other endocrinologic disorders (for example, Cushing Syndrome) or diagnosed monogenetic or syndromic forms of obesity (for example, Melanocortin 4 Receptor deficiency or Prader-Willi Syndrome). * A self-reported reduction in body weight of more than 5 kg within 30 days before screening, irrespective of medical records. * Treatment with any medication for the indication of obesity within the past 90 days before screening (e.g., Orlistat, liraglutide, naltrexone/bupropion, diethylpropion, phendimetrazine, semaglutide, and setmelanotide). * Any previous obesity treatment with surgery or a weight loss device during a lifetime. * Continued treatment with other GLP-1 agonists, SGLT-2 inhibitors, and/or metformin. However, if these drugs can be stopped based on the best clinical judgment of the investigator, the patient can be recruited after stopping the drug and a washout period of two weeks. In the case of tirzepatide, the washout period will be 8 weeks. * Are receiving or have received within 3 months prior to screening chronic (\>2 weeks or 14 days) systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, intra-articular, or inhaled preparations) or have evidence of a significant, active autoimmune abnormality (for example, lupus or rheumatoid arthritis). * Have current or history of (within 3 months prior to enrollment) treatment with medications that may cause significant weight gain, including but not limited to tricyclic antidepressants, atypical antipsychotics, and mood stabilizers. * Have started implantable or injectable contraceptives (such as Depo-Provera®) within 18 months prior to screening. * Past history of pancreatitis. * Diagnosed case of eating disorders (e.g., Bulimia nervosa). * Patients with a previous history of suicide attempts and major depressive disorder (MDD) according to DSM-V criteria, schizophrenia, or antipsychotic drug-induced obesity. * Patients with a personal or family history of medullary thyroid carcinoma (MTC) and/or multiple endocrine neoplasia syndrome type 2 (MEN 2). * Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years. * Have uncontrolled hypertension (SBP ≥160 mmHg and/or DBP ≥100 mmHg). * Have NYHA Functional Classification IV CHF. * Have had a transplanted organ (corneal transplants \[keratoplasty\] allowed) or awaiting an organ transplant. * Laboratory criteria: * Incidental diagnosis or uncontrolled thyroid disease, defined as a thyroid-stimulating hormone (TSH) level \>6.0 mIU/L or \<0.4 mIU/L as measured by the central laboratory at screening. However, well-controlled thyroid disorder can be included if TSH \<6.0 or \>0.4 mIU/L. * Renal impairment, measured as the estimated glomerular filtration rate (eGFR) \<15 ml/min/1.73 m². For subjects without T2DM: \- HbA1c more than or equal to 48 mmol/mol (6.5%). For subjects with T2DM: * Renal impairment, defined as an estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m² (less than 60 mL/min/1.73 m² in subjects treated with a sodium-glucose cotransporter 2 inhibitor (SGLT2i)). * Uncontrolled T2DM (HbA1c \>10.0%) as these patients may require insulin or other anti-diabetic drugs which might potentially interfere with the efficacy of tirzepatide.