Abstract / Summary
Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/GIP agonists have transformed obesity and diabetes care, but rapid weight regain and partial reversal of cardiometabolic gains follow discontinuation. In India, rebound occurs on a high-risk substrate of central adiposity, thin-fat and sarcopenic-obesity phenotypes and dense metabolic obesity at lower BMI, so even modest off-drug weight or waist increases may accelerate glycaemic and vascular deterioration. Methods: This narrative review integrates randomised trials and real-world cohorts of GLP-1/GLP-1–GIP tapering or withdrawal, metabolic/bariatric surgery data, and Indian epidemiological, body-composition and pharmacogenomic studies. We searched major databases to March 2026 for studies on incretin discontinuation, weight rebound, Indian obesity phenotypes, sarcopenic and abdominal obesity and incretin-pathway variants (TCF7L2, ADIPOQ, ARRB1), and reviewed National Family Health Survey-5 (NFHS-5) and Indian Council of Medical Research–India Diabetes Study (ICMR–INDIAB) datasets. Results: Across STEP-1, SURPASS-1 and SURMOUNT-CN, approximately two-thirds of prior weight loss is regained within 6–12 months of withdrawal, with glycated haemoglobin (HbA1c) and weight drifting within weeks. Indian data show high prevalence of abdominal obesity and sarcopenic obesity in type 2 diabetes, and rare metabolically healthy obesity. Thin-fat and sarcopenic phenotypes, with TCF7L2/ADIPOQ/ARRB1-linked vulnerability, suggest fat regain and lean-mass loss may precipitate disproportionate relapse. Metabolic/bariatric surgery and incretin therapy are bidirectional partners: incretins optimise peri-operative risk and weight courses, while surgery provides durable support when drugs are tapered. Conclusion: In India, post-GLP-1 weight rebound should be managed as a high-risk cardiometabolic transition. A planned, phenotype-directed strategy of avoiding abrupt withdrawal, leveraging bariatric–incretin synergy, waist-first and HbA1c-first surveillance, and maintaining lean mass can compress relapse and sustain organ protection.