Efficacy and Safety of GLP ‐1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA

ABSTRACT Objective To compare the efficacy and safety of GLP‐1 receptor agonists (GLP‐1RAs), dual agonists (GLP‐1RAs/GIP or GCGR), and retatrutide (GLP‐1/GIP/glucagon) for weight loss in adults with overweight or obesity. Methods We conducted a systematic review and Bayesian network meta‐analysis (NMA) of 19 randomized controlled trials (RCTs) including 29,506 adults (BMI ≥ 25 kg/m 2 ), assessing liraglutide, semaglutide, survodutide, tirzepatide, retatrutide, and placebo. Outcomes included mean weight loss, achievement of ≥ 5%, ≥ 10%, and ≥ 15% weight loss, waist circumference (WC), BMI, and adverse events (AEs) at ≥ 36 weeks. Subgroup and meta‐regression analyses evaluated the impact of diabetes status, sex, age, and BMI. Results Retatrutide and dual agonists achieved equivalent mean weight loss (−11.0 kg), surpassing GLP‐1RAs (−9.0 kg), with retatrutide excelling at achieving ≥ 15% weight loss (OR 54.6). Dual agonists and GLP‐1RAs followed (OR 16.4 and 9.0, respectively). Retatrutide had the highest AE risk. Meta‐regression showed type 2 diabetes mellitus (T2DM) reduced weight loss by 4.338 kg for GLP‐1RAs and 5.016 kg for dual agonists, with enhanced outcomes in female‐dominant or high‐BMI cohorts. Conclusions Retatrutide offers superior weight loss efficacy but with a higher AE risk. Dual agonists provide a favorable efficacy–safety balance. Personalized treatment selection based on patient characteristics is recommended. image