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

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/m2), 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.