GLP-1 drugs have rapidly grown in use for their strong effects on weight loss, changing how clinicians approach obesity treatment. Two commonly used types are semaglutide (examples: Ozempic, Wegovy) and tirzepatide (examples: Mounjaro, Zepbound). A recent preprint on medRxiv suggests tirzepatide may lead to greater reductions in lean body mass than semaglutide.
What the study did and found
– The analysis included 7,965 people who were starting a GLP-1 medication for the first time: 6,196 began semaglutide and 1,769 began tirzepatide.
– Researchers measured lean body mass before treatment and during follow-up after the first prescription.
– People taking tirzepatide lost more lean body mass than those taking semaglutide: about 1.1% more loss in the first 3 months, increasing to about 2% more by 12 months.
– Approximately 10% of tirzepatide users achieved a 20% total weight reduction and a 5% reduction in lean body mass; for semaglutide users, about 7% reached those thresholds.
Context and interpretation
– Lean body mass includes muscle, connective tissue, and other tissues that support metabolism, strength, and function.
– The study is a preprint and has not yet undergone peer review.
– Experts note the result is consistent with tirzepatide’s generally greater potency for weight loss. Greater overall weight loss often comes with higher relative loss of lean mass as well. “The more aggressive the weight loss, the greater the likelihood that some of that loss includes muscle, not just fat,” said Jeffrey Lee, MD (who was not involved in the study).
Factors linked to higher lean mass loss
– Higher medication doses and longer treatment duration
– Reduced ability or tolerance for exercise during treatment
– Pre-existing musculoskeletal conditions
Preserving muscle while on GLP-1s
– Exercise, especially resistance (strength) training, helps signal the body to maintain muscle even in a calorie deficit and is key to preserving lean mass while losing weight.
– Adequate protein intake supports muscle maintenance.
– A slower, more gradual pace of weight loss tends to preserve lean mass better than rapid loss; careful dose titration and monitoring are important.
Bottom line
Tirzepatide appears associated with somewhat greater lean body mass loss than semaglutide, likely related to its stronger weight-loss effects. Patients using GLP-1 medications should prioritize strength training, sufficient protein, and monitored, gradual weight loss to reduce muscle loss risk.
