'Musclezempic' Trials Show Promise
New clinical trials suggest combining GLP-1 drugs with muscle-boosting agents could transform weight loss by offering simultaneous fat loss and muscle preservation. The "Musclezempic" approach addresses the muscle loss problem common with current weight loss medications.
One promising drug combination, Eli Lilly's bimagrumab with semaglutide, showed in the BELIEVE trial that 92.8% of total weight lost came from fat, compared to 71.8% with semaglutide alone. The combination group experienced a minimal 2.9% loss of lean mass, a significant improvement over the 7.4% lean mass loss with semaglutide by itself. Bimagrumab works by blocking activin type II receptors, which are proteins that signal the body to break down muscle. This mechanism promotes muscle growth and increases fat oxidation independently of appetite suppression. Common side effects associated with bimagrumab in trials have included muscle spasms, diarrhea, and acne. Another approach comes from Veru Inc., which is testing its oral drug enobosarm alongside GLP-1 medications. Enobosarm is a selective androgen receptor modulator (SARM) that targets androgen receptors in muscle to promote growth and prevent breakdown. In a phase 2b trial with older adults taking Wegovy, the enobosarm group lost only 1.2% of their lean body mass compared to a 4.1% loss in the Wegovy-only group over 16 weeks. While the "Musclezempic" field shows promise, it has also faced setbacks. In late 2024, BioAge Labs halted its Phase 2 trial of azelaprag combined with tirzepatide after some participants developed elevated liver enzymes. More recently, Eli Lilly discontinued a Phase IIb study combining bimagrumab with its own powerful weight-loss drug, tirzepatide (Zepbound), citing "strategic business reasons." Eli Lilly is also developing retatrutide, a next-generation drug that mimics three different hunger-related hormones: GLP-1, GIP, and glucagon. In a Phase 3 trial, it led to an average weight loss of 28.7% (about 71 pounds) over 68 weeks. Further results from its comprehensive TRIUMPH trial program are expected throughout 2026, with a potential FDA approval timeline around 2027.
