A systematic review of 26 randomized controlled trials has found that retatrutide, an experimental drug being investigated by Eli Lilly and Company, produces the greatest weight loss among glucagon-like peptide 1 (GLP-1) receptor agonists and co-agonists. The review examined commercially available medications and nine investigational agents, evaluating their effectiveness in reducing body weight.
Among healthy adults with overweight or obesity without diabetes, retatrutide achieved the highest mean reductions in relative and absolute body weight after 48 weeks of treatment, followed by tirzepatide and semaglutide. The study found that patients taking retatrutide lost 22% of their body weight, while those on tirzepatide and semaglutide lost 18% and 14%, respectively.
The review also showed that dual and triple GLP-1 agonists generally reported greater mean weight losses than single GLP-1 agonists. However, the authors cautioned against drawing conclusions about comparative efficacy due to differences in study populations, control groups, and contexts.
Notably, four investigational drugs did not produce significant weight loss: Beinaglutide, efpeglenatide, exenatide, and noiiglutide. The most common adverse events among all GLP-1s were gastrointestinal symptoms such as nausea, diarrhea, constipation, and vomiting.
The study suggests that GLP-1s would have to be used chronically to achieve the greatest effect, with longer treatment durations demonstrating similar weight loss results.
Source: https://www.medscape.com/viewarticle/retatrutide-produces-greatest-weight-loss-2025a100009a?form=fpf