A new study comparing tirzepatide vs semaglutide is drawing attention after researchers reported that Eli Lilly’s tirzepatide may lead to greater average weight loss than Novo Nordisk’s semaglutide, but with a higher loss of lean body mass. The findings were reported this week ahead of peer review, making the study notable but still preliminary.
Tirzepatide is sold under the brand names Zepbound and Mounjaro, while semaglutide is marketed under the brand names Wegovy and Ozempic. Both drugs have become widely used for weight loss and metabolic treatment, but concerns have persisted about how much muscle and connective tissue patients may lose alongside fat.
Researchers analysed data from roughly 1,800 patients treated with tirzepatide and 6,200 treated with semaglutide. They found that tirzepatide was consistently associated with greater lean body mass loss, with an average difference of 1.1% after 3 months and 2% after 12 months of continuous use.
Tirzepatide Vs Semaglutide Study Finds Bigger Trade-Off
The reported results suggest that greater weight loss may not be the only factor patients and clinicians consider when comparing the two drugs. The study leader, Venky Soundararajan of nference, said the data suggest that people should not focus solely on which medicine delivers the largest weight reduction.
Researchers tracked patients before and during treatment using either low-radiation scans or smart scales that estimate body fat percentage, muscle mass, bone mass, and other body composition measures. However, the study did not explain why tirzepatide appeared to produce greater lean mass loss than semaglutide.
Tirzepatide mimics both GLP-1 and GIP hormones, while semaglutide mimics only GLP-1. Both drugs slow digestion and increase feelings of fullness.
The study reported that roughly 10% of tirzepatide users who lost more than 20% of total body weight also lost more than 5% of lean body mass. Among semaglutide users with the same degree of weight loss, that figure was under 7%.
Researchers also found that reduced exercise tolerance during treatment was associated with greater lean body mass loss in both groups, though the association was stronger among patients treated with tirzepatide. Higher doses, longer treatment duration, and preexisting musculoskeletal pain were also connected to a greater decline in lean mass.
That pattern led the study authors to describe a possible cycle in which patients with preexisting musculoskeletal issues may exercise less during treatment, potentially contributing to further lean body mass decline.
Novo Nordisk did not comment directly on the study, though a spokesperson pointed to clinical trials in which changes in muscle mass did not significantly differ between semaglutide and placebo, while physical function remained preserved. Lilly did not immediately respond to a request for comment.
