<ul>
<li>GLP-1 drugs yielding greater weight loss have worse effects on lean body mass</li>
<li>Patients on tirzepatide lost more muscle and other non-fat tissues than patients on semaglutide</li>
<li>Exercise during treatment is essential with both drugs, researchers say</li>
</ul>
By Nancy Lapid
April 16 (Reuters) - Eli Lilly’s (LLY.N) GLP-1 drug tirzepatide yields greater weight loss on average than Novo Nordisk’s (NOVOb.CO) semaglutide, but at a greater expense to muscles and connective tissues, according to a study published this week ahead of peer review.
Tirzepatide, sold as Zepbound and Mounjaro, and semaglutide, under the brand names Wegovy and Ozempic, have become wildly popular for weight loss and have demonstrated other health benefits, such as heart-protective properties. But there has been concern that they induce loss of muscle and other components of lean body mass along with fat.
The researchers analyzed data on roughly 1,800 patients using tirzepatide and 6,200 using semaglutide.
Tirzepatide was consistently associated with greater loss of lean body mass than semaglutide. Tirzepatide patients lost an average of 1.1% more lean body mass after three months and 2% after 12 months of continuous use, the analysis by Massachusetts-based data analytics firm nference found.
“This suggests that patients shouldn’t simplistically be thinking, ‘I want to lose X amount of weight and I’ll go with the option that delivers greater weight loss,’” said study leader Venky Soundararajan of nference on the study data published online.
Patients were tracked before and during treatment either with low radiation scans or with “smart” scales that estimate body fat percentage, muscle mass, bone mass, and other components.
The study cannot explain why lean body mass loss was greater with tirzepatide, which mimics the hormones GLP-1 and GIP, compared with semaglutide, which only mimics GLP-1. Mimicking the hormones slows digestion and makes patients feel full.
A Novo spokesperson did not comment on the current study but said changes in muscle mass did not significantly differ between semaglutide and placebo groups in clinical trials, and physical function was preserved. Lilly did not immediately respond to a request for comment.
<h3>STUDY DETAILS</h3>
Roughly 10% of tirzepatide users who lost more than 20% of their total body weight were found to have lost more than 5% of their lean body mass. That was true for fewer than 7% of semaglutide users who lost the same percentage of body weight.
Decreased exercise tolerance during treatment was linked with greater lean body mass loss in both groups, but to a greater extent in tirzepatide-treated patients.
Higher doses, longer treatment, and the presence of musculoskeletal pain before treatment began were also associated with greater lean body mass decline with both drugs, the researchers found.
“It’s a vicious cycle,” Soundararajan said. “If you start with a drug which puts you at a greater probability of lean body mass loss… and you have a preexisting history of musculoskeletal diseases, it puts you at greater risk of lower tolerance to exercise. And if you’re not exercising when you’re on these medicines, you are essentially causing attrition of lean body mass.”
nference funding comes from health systems, institutional investors, and venture capital firms.

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Novo weight-loss drug may preserve lean body mass better than Lilly's, study finds