The Medical Advisor

Evidence review | Updated October 28, 2026 CagriSema and retatrutide are two investigational medicines generating substantial interest in obesity treatment. Both target multiple hormonal pathways involved in appetite, metabolism and body-weight regulation, but their mechanisms are different. CagriSema combines semaglutide, a GLP-1 receptor agonist, with cagrilintide, a long-acting amylin analogue. Retatrutide is a single molecule that activates three receptors: GIP, GLP-1 and glucagon. Phase 3 results reported in 2026 suggest that retatrutide may produce greater average weight loss than the results reported for standard-dose CagriSema. However, there is no completed direct head-to-head trial establishing that retatrutide is superior to CagriSema. Differences in trial duration, populations, dose escalation and statistical analyses prevent a definitive ranking. Muscle preservation is another important distinction. Available body-c...

Medically Reviewed by: Dr. Frank Yap, MD | Written by: OneDayMD Editorial Team | Published: March 2026 | Last updated: October 2026 Quick Answer Semaglutide (“sema”), tirzepatide (“tirz”), and retatrutide (“reta”) represent three stages in the evolution of incretin-based weight-loss medications: a single GLP-1 receptor agonist, a dual GIP/GLP-1 receptor agonist, and an investigational triple GIP/GLP-1/glucagon receptor agonist, respectively. Semaglutide is an FDA-approved GLP-1 receptor agonist that has demonstrated average weight loss of approximately 15% in clinical trials, with some individuals losing more. Tirzepatide, a dual GIP/GLP-1 receptor agonist, has demonstrated average weight loss of up to approximately 21–22% in trials. Retatrutide, an investigational triple agonist targeting GIP, GLP-1, and glucagon receptors, has shown promising weight-loss results in clinical trials but is not yet FDA-approved. What changed in this update (Oct 2026): replaced pre-Phase-3 esti...

Last updated: October 2026 Retatrutide and CagriSema are investigational obesity treatments that can produce substantial weight loss through different hormonal mechanisms. But for people who want to reduce body fat without sacrificing muscle, the scale alone does not tell the whole story. The critical question is not simply which treatment produces the greatest weight reduction. It is how much of that reduction comes from fat, how much comes from lean tissue, and whether the treatment helps people maintain muscle strength and physical function throughout the process. Existing clinical evidence provides some insight into body-composition changes with both treatments. However, there is currently insufficient evidence to establish that retatrutide or CagriSema preserves more muscle than the other. This review examines the published clinical evidence, explains what body-composition measurements can and cannot tell us, and outlines practical strategies for protecting muscle du...