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

Obesity (Silver Spring, Md.) Pub Date : 2025-07-20 DOI:10.1002/oby.24360

Binayak Sinha, Samit Ghosal

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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/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.

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GLP-1受体激动剂、双重激动剂和利特鲁肽对超重或肥胖成人减肥的有效性和安全性：贝叶斯NMA

目的：比较GLP-1受体激动剂（GLP-1RAs）、双激动剂（GLP-1RAs/GIP或GCGR）和利特鲁肽（GLP-1/GIP/胰高血糖素）对超重或肥胖成人减肥的疗效和安全性。方法：我们对19项随机对照试验（RCTs）进行了系统回顾和贝叶斯网络荟萃分析（NMA），包括29,506名成年人（BMI≥25 kg/m2），评估利拉鲁肽、西马鲁肽、利托肽类、替西帕肽、利特鲁肽和安慰剂。结果包括平均体重减轻，体重减轻≥5%，≥10%和≥15%，腰围（WC）， BMI和不良事件(ae)≥36周。亚组和荟萃回归分析评估了糖尿病状况、性别、年龄和BMI的影响。结果：利特鲁肽和双激动剂实现了等效的平均体重减轻（-11.0 kg），超过GLP-1RAs (-9.0 kg)，其中利特鲁肽在达到≥15%的体重减轻（OR 54.6）方面表现出色。其次是双激动剂和GLP-1RAs （OR分别为16.4和9.0）。利托鲁肽的AE风险最高。荟萃回归显示，2型糖尿病（T2DM） GLP-1RAs组体重减轻4.338 kg，双激动剂组体重减轻5.016 kg，在女性占主导地位或高bmi队列中，结果有所改善。结论：利托鲁肽具有较好的减肥效果，但有较高的AE风险。双重激动剂提供了良好的疗效-安全性平衡。建议根据患者特点选择个性化治疗方案。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Obesity (Silver Spring, Md.)

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