Retatrutide delivers superior weight loss in adults with obesity

Treatment with retatrutide demonstrates superiority over GLP-1 receptor agonists (RAs) and dual agonists (GLP-1 RAs/GIP or GCGR) in terms of weight loss in adults with overweight or obesity, but it also results in a greater risk of adverse events (AEs), according to a study.

Nineteen randomized controlled trials (RCTs), including a total of 29,506 adults (BMI ≥25 kg/m2), assessing liraglutide, semaglutide, survodutide, tirzepatide, retatrutide, and placebo were included in this systematic review and Bayesian network meta-analysis.

The investigators assessed the following outcomes at ≥36 weeks: weight loss; achievement of ≥5 percent, ≥10 percent, and ≥15 percent weight loss; waist circumference (WC); BMI; and AEs. They also performed subgroup and meta-regression analyses to assess the impact of diabetes status, sex, age, and BMI.

Both retatrutide and dual agonists surpassed GLP-1 RAs in mean weight loss (‒11 vs ‒9.0 kg), with retatrutide achieving ≥15-percent weight loss (odds ratio, 54.6). This was followed by dual agonists (OR, 16.4) and GLP-1 RAs (OR, 9.0).

However, the use of retatrutide also led to the highest AE risk. In meta-regression, type 2 diabetes mellitus reduced weight loss by 4.338 kg for GLP-1 RAs and 5.016 kg for dual agonists, with improved outcomes in female-dominant or high-BMI cohorts.

“Dual agonists provide a favorable efficacy–safety balance,” the investigators said. “Personalized treatment selection based on patient characteristics is recommended.”