Efficacy of Tirzepatide for Weight Management in Patients With Suboptimal Weight Loss After Bariatric Surgery: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Inclusion Criteria: 1. Adults (male or female) aged ≥18 years. 2. History of bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) performed ≥12 months before enrollment. 3. Current BMI ≥30 kg/m². 4. Evidence of suboptimal weight loss, defined as percentage total weight loss (%TWL) since surgery of less than 25% (defined as the percentage of weight loss comparing current body weight with body weight before surgery). 5. Absence of recent weight loss (defined as \<5% reduction in body weight over the 6 months prior to screening); participants may be weight stable (\<5% variation in body weight over the 6 months prior to screening) or have experienced weight gain. 6. In the investigator's opinion, well-motivated, capable, and willing to comply with study procedures. 7. For 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 study drug plus 90 days, corresponding to 4 months after the last injection. 8. For female participants: a. Female participants not of childbearing potential may participate and include those who are: i. infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy or tubal ligation), congenital anomaly such as Mullerian agenesis ii. 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 ≥40mIU/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 b. Female participants of child-bearing 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 9. Provision of written informed consent prior to any study-specific procedures. Exclusion Criteria: 1. Use of a GLP-1 receptor agonist (GLP-1 RA) or any other GLP-1-based therapy at present or within the past 6 months. 2. Prescription of a GLP-1 RA or other GLP-1-based therapy within the past 12 months that could not be initiated or maintained due to drug supply shortages. 3. Have a planned surgical treatment, endoscopic and/or device-based therapy for obesity during the period of the study. 4. History of type 1 diabetes or uncontrolled type 2 diabetes (HbA1c \>10%). 5. Type 2 diabetes currently treated with insulin or sulfonylureas. 6. Have a known clinically significant gastric emptying abnormality (for example, severe diabetic gastroparesis or gastric outlet obstruction) or chronically take drugs that directly affect GI motility. 7. Have had a history of chronic or acute pancreatitis. 8. Have NYHA Functional Classification III or IV heart failure. 9. Have thyroid-stimulating hormone (TSH) outside of the reference range at screening visit. 10. 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). 11. Have a history of significant active or unstable Major Depressive Disorder or other severe psychiatric disorder (for example, schizophrenia, bipolar disorder, or other serious mood or anxiety disorder) within the last 2 years. 12. Have any lifetime history of a suicide attempt. 13. Have a family or personal history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia (MEN) Syndrome type 2. 14. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site). 15. Participation in another clinical study with an investigational product during the last month. 16. Unwilling or unable to sign the informed consent form. 17. History of active malignancy within the past 5 years (except adequately treated non-melanoma skin cancer or in situ carcinoma of the cervix). 18. Known hypersensitivity or contraindication to tirzepatide or any of its excipients. 19. Have severe hepatic impairment (Child-Pugh class C). 20. Have severe renal impairment (eGFR \<30 mL/min/1.73 m² using CKD-EPI formula). 21. 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) that has required (within the last 3 months) or is likely to require, in the opinion of the investigator, concurrent treatment with systemic glucocorticoids (excluding topical, intraocular, intranasal, intra-articular or inhaled preparations) in the next 12 months. 22. For female patients, pregnancy, breastfeeding, or planning pregnancy during the study period. 23. Any condition which, in the investigator's opinion, may jeopardize the subject's safety or compliance with the protocol (e.g., severe psychiatric illness, alcohol or substance abuse).