Meta-analysis of semaglutide and tirzepatide trials finds lean mass is 25% to 39% of weight lost

A systematic review and meta-analysis of 20 randomized controlled trials has put specific numbers on how much of the weight people lose on incretin-based drugs comes from lean mass rather than fat. The analysis, published March 24, 2026, in the journal Diabetes, Obesity and Metabolism, pooled 15,782 participants and found that lean mass made up 25% to 39% of the weight lost with these drugs ^[1].

Among the drugs studied, semaglutide (sold as Ozempic, Wegovy and Rybelsus) showed the highest share: lean mass accounted for 35.2% of total weight lost, with a 95% confidence interval of 31.5 to 38.9. Tirzepatide (Mounjaro and Zepbound) came in at 25.4% (22.8 to 28.0), and liraglutide at 26.8% (23.1 to 30.5) ^[1].

Lifestyle programs without drugs produced a similar proportion: 26.2% (24.1 to 28.3). The authors reported no statistically significant difference between the drug groups and the lifestyle-only group, with a p value of 0.42 for that comparison. The most favorable result in the analysis came from lifestyle intervention combined with resistance training, where lean mass made up 17.5% of weight lost (14.2 to 20.8) ^[1].

The authors searched PubMed, Embase, Cochrane CENTRAL and Web of Science through January 20, 2026, for randomized trials of semaglutide, tirzepatide, liraglutide or lifestyle interventions that measured body composition with dual-energy X-ray absorptiometry or magnetic resonance imaging. The two main outcomes were the absolute change in lean mass in kilograms and the share of total weight loss made up of lean mass. The published summary reports the proportions; the kilogram figures are not included in it ^[1].

Heterogeneity across the pooled trials was moderate (I² = 68%), and the authors reported no indication of publication bias (Egger's test p = 0.23). The review protocol was registered with PROSPERO, and the authors declared no conflicts of interest ^[1].

The study pooled 20 separate trials rather than randomly assigning participants within a single study to a drug alone or a drug plus training, so the comparison involving the resistance-training group rests on differences between trials as well as between treatments. The published summary does not report which resistance-training programs were used, how often participants trained, or how much protein they ate ^[1]. It also does not report whether preserving lean mass changes longer-term outcomes such as physical function, falls or weight regain ^[1].

Why it matters for patients

Lean mass includes muscle. Based on the pooled proportions, for every 10 pounds lost on these drugs, roughly 2.5 to 3.9 pounds came from lean tissue. People losing weight through lifestyle programs alone lost lean mass at a broadly comparable rate, so in this analysis the drug itself did not change the proportion of weight lost as lean mass ^[1].

The difference appeared when resistance training was added to a lifestyle program, which was linked to a smaller share of weight lost as lean mass. That lines up with the authors' conclusion that muscle can be preserved by combining resistance training, adequate protein intake and body composition monitoring into weight-loss treatment programs ^[1]. The analysis did not test a specific protein target, training dose or monitoring schedule, so it does not establish how much of each is needed ^[1].

The trials covered adults with overweight or obesity. Whether the same proportions apply to people taking these drugs for other reasons, such as type 2 diabetes or cardiovascular risk reduction, is not addressed in the published summary ^[1].

The review also does not include the absolute kilogram changes in lean mass, which were one of the two main outcomes the authors set out to measure. How many pounds of lean mass a person loses depends on how much weight they lose overall, and that calculation cannot be made from the proportions reported here ^[1].