A new systematic review of 26 randomized controlled trials (RCTs) found that retruttide, an experimental drug developed by Eli Lilly and Company, produces the greatest weight loss among glucagon-like peptide 1 (GLP-1) receptor agonists and co-agonists.
The study, conducted by researchers at McGill University in Canada, examined commercially available medications in the class and nine investigational agents. The review found that retruttide, given once-weekly as a triple glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, resulted in a 22% reduction in body weight after 48 weeks.
Tirzepatide and semaglutide, both commercially available dual GLP-1 agonists, also showed significant weight loss, with losses of 18% and 14%, respectively. Patients taking liraglutide, another commercially available medication, lost up to 6% of body weight after 26 weeks.
The study’s findings suggest that retruttide may be the most effective GLP-1 agent for weight loss, particularly when used as part of a comprehensive treatment plan including lifestyle modification. However, it is essential to note that the populations, control groups, and contexts of the various studies might not be directly comparable.
The review also found that patients taking investigational agents such as survodutide and mazdutide experienced significant weight loss, ranging from 6% to 15%. Orforglipron, a once-daily pill, produced weight loss of 9%-15%, depending on the dose.
Common adverse events associated with GLP-1 medications included gastrointestinal issues, which were typically transient. However, some patients discontinued treatment due to side effects, and no serious GI disorders were reported in any of the trials.
The study’s authors noted that chronic use may be necessary to achieve optimal weight loss results with GLP-1 agents.
Source: https://www.medscape.com/viewarticle/retatrutide-produces-greatest-weight-loss-2025a100009a