Efficacy and Safety of Tirzepatide for Weight Management

Exclusion Criteria

• •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.