1684-P: Comparative Efficacy and Tolerability of Incretin-Based Medication for Weight Loss in Adults with Overweight or Obesity: A Meta-Analysis of Randomized Controlled Trials

Introduction and Objective: Glucagon-like peptide-1 receptor-agonists (GLP-1 RAs) and the dual GIP/GLP-1 receptor agonist tirzepatide, when used for the pharmacological treatment of obesity, have become substantially more effective (tirzepatide semaglutide liraglutide) regarding weight reduction. We wanted to systematically study the impact on adverse events. Methods: We conducted a meta-analysis of randomized, placebo-controlled trials evaluating liraglutide 3 mg once daily, semaglutide 2.4 mg once weekly, and tirzepatide 15 mg once weekly in adults with overweight or obesity. Outcomes included placebo-subtracted body weight reduction and odds ratios for gastrointestinal adverse events, treatment discontinuation, and hypoglycemia. Results: Nineteen RCT including 13,508 participants were analyzed. Mean weight loss was −5.3% (95% CI −5.6 to −4.9) with liraglutide, −12.0% (−12.4 to −11.5) with semaglutide, and −14.6% (−15.5 to −13.8) with tirzepatide (all p0.0001). Weight reduction with semaglutide and tirzepatide was dose-dependent across the full dose range. Odds ratios for nausea were 4.0 (95% CI 3.4-4.6), 2.7 (2.3-3.1), and 3.9 (3.2-5.0), and for vomiting 4.5 (3.6-5.7), 3.5 (2.9-4.3), and 6.0 (4.1-8.8) for liraglutide, semaglutide, and tirzepatide, respectively. Treatment discontinuation occurred in 8.4% (L), 3.7% (S), and 2.8% (T). Hypoglycemia was rare and severe events were not reported. Conclusion: Marked and significant differences in weight-reducing efficacy exist among incretin-based therapies, whereas risks of gastrointestinal AE, treatment discontinuation, and hypoglycemia are broadly comparable, likely reflecting dose-escalation strategies that improve tolerability. Disclosure S. Al Basri: None. M.A. Nauck: Advisory Panel; Current; Boehringer Ingelheim International GmbH, Eli Lilly and Company. Speaker's Bureau; Current; Novo Nordisk. Advisory Panel; Current; Pfizer Inc., Regor. Consultant; Current; Structure Therapy. Speaker's Bureau; Current; Eli Lilly and Company, Novo Nordisk, Medscape, Medical Learning Institute. Advisory Panel; Current; Sun Pharmaceutical Industries Ltd. W. Fenske: Advisory Panel; Current; Lilly Global Health Partnership, Boehringer Ingelheim International GmbH, Novo Nordisk. Other - Speaker; Current; Amgen Inc.