Muscle Loss on Semaglutide vs Tirzepatide: What the Body Scans Show, and What Strength Training Adds

What the body scans show

Two of the main obesity trials had DXA body-scan substudies. In the STEP 1 substudy, semaglutide 2.4 mg reduced total fat mass by about 10.4 kg and lean mass by about 6.9 kg, so roughly 60% of the weight lost was fat and 40% lean, as summarized in the SURMOUNT-1 substudy report ^[1].

In the SURMOUNT-1 substudy (160 adults, 73% women), tirzepatide reduced body weight by 21.3%, fat mass by 33.9% and lean mass by 10.9% over 72 weeks, against 5.3%, 8.2% and 2.6% on placebo; about 25% of the weight lost was lean in both groups ^[1]. These are separate trials with different people, so the two splits are not a head-to-head comparison.

Lean mass is not all muscle

Lean mass on a DXA scan includes organs, bone, fluids and the water inside fat tissue, not only muscle. Reported lean-mass losses with GLP-1 drugs range from about 15% or less of the weight lost to 40% to 60%, and MRI studies suggest muscle changes are largely in line with the weight lost, with muscle quality likely improving as insulin sensitivity improves ^[3].

The 2026 meta-analysis found the share of weight lost as lean mass was broadly similar on incretin drugs and in lifestyle programs (26.2%), while programs that added resistance training lost the smallest share (17.5%) ^[2]. The same review notes that older age and more severe disease raise the stakes for losing muscle ^[3].

What resistance training adds during weight loss

In a 2018 meta-analysis of six randomized trials in older adults with obesity, adding resistance training three times a week to a calorie-restricted diet prevented about 93.5% of the lean-mass loss seen with diet alone (about 0.8 kg), with similar fat loss ^[4].

In a 2017 trial of 160 dieting older adults with obesity, everyone who exercised lost about 9% of body weight, but lean mass fell 2% to 3% with resistance or combined training versus 5% with aerobic training alone, and strength rose about 18% to 19% ^[5].

A 2022 meta-analysis of 65 trials in adults with overweight or obesity found resistance programs added about 0.8 kg of lean mass on average; programs that combined resistance training with calorie restriction were associated with reductions in lean mass ^[9].

A trial that paired a GLP-1 drug with exercise

In a Danish randomized trial, 195 adults first lost about 13 kg on an 8-week low-calorie diet, then spent a year on exercise, liraglutide 3.0 mg, both, or placebo. Over that year the combination group lost 9.5 kg more than placebo and cut body-fat percentage by 3.9 points, about twice as much as either treatment alone ^[6].

In the same trial, hip and spine bone density in the combination group did not change compared with placebo, while liraglutide alone lowered bone density more than exercise alone despite similar weight loss ^[7]. Liraglutide is an older, less potent drug than semaglutide or tirzepatide, so these results may not carry over exactly.

What the guidance recommends

The 2025 joint advisory from four US obesity and nutrition societies says GLP-1s should be prescribed together with a structured exercise program: strength training at least 3 times a week plus at least 150 minutes a week of moderate aerobic activity, matched to the person’s fitness ^[8]. It adds that more protein alone is likely inadequate to preserve muscle without strength training ^[8].

For the protein side, see our protein targets on a GLP-1. Women-specific figures are in our GLP-1 muscle guide for women, and our creatine monograph covers the trials of creatine with strength training.