Ozempic and Mounjaro Muscle Loss: 28% of the Weight, Across 35 Studies
Quick Answer: Yes, semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) cause some muscle loss, because most large weight losses do. A 2026 systematic review of 35 studies found that a median of 28.3% of the weight people lost on these drugs came from muscle-based measures (interquartile range 15.9% to 39.9%), and that about two thirds of studies exceeded the roughly 25% expected from weight loss alone. Two findings soften that number. First, no study measured physical function, so whether people became weaker is unknown. Second, in an MRI analysis of tirzepatide, the fat inside thigh muscle fell, and experts reading the MRI studies describe the muscle change as largely “adaptive.” The protection with the best evidence is the same as for age-related muscle loss: resistance training and enough protein.
GLP-1 drugs produce weight loss on a scale previously seen only after surgery: in the main trials, about 15% of body weight with semaglutide 2.4 mg over 68 weeks and with tirzepatide 5 mg over 72 weeks. With that much loss, the question of what the lost kilograms are made of matters, especially for older adults who start with less muscle. This page sets out what has been measured, where the uncertainty is, and what you can do about it.
How much of the weight lost is muscle?
The most complete answer comes from a 2026 systematic review in the Annals of Internal Medicine that pooled 35 studies of liraglutide, semaglutide, tirzepatide and dulaglutide in adults, with a median duration of 26 weeks.
| Measurement | Median share of weight lost from muscle-based measures | Studies above the expected benchmark |
|---|---|---|
| All methods | 28.3% (IQR 15.9% to 39.9%) | 65% (benchmark about 25%) |
| DXA or bioimpedance (lean or fat-free mass) | About 29% (IQR 16.6% to 43.1%) | 67% (benchmark about 25%) |
| CT or MRI (skeletal muscle) | About 25.3% (IQR 16.7% to 27.2%) | Two thirds (benchmark about 15%) |
The authors’ conclusion: loss of muscle-related measures exceeded the benchmarks “in about two thirds of incretin-based interventions and in nearly half of nonpharmacologic interventions that produced weight loss.” In other words, diet-only weight loss also costs muscle, and the drug groups lost much more weight: the lifestyle or placebo comparators lost a median of only 2.5%.
The review is also blunt about what it could not answer: “no study reported objective physical function outcomes,” and differences in methods “precluded meta-analysis.”
Why the numbers in the news vary so much
A 2024 review in Diabetes, Obesity and Metabolism noted that in some trials lean mass made up 40% to 60% of the weight lost, while in others it was 15% or less. One reason is what is being measured. “Lean mass” on a DXA scan “includes not only muscle but also organs, bone, fluids, and water in fat tissue,” so it overstates muscle loss compared with an MRI of the muscle itself. That is why the CT and MRI studies in the table above show a lower share than the DXA studies.
Is the muscle that remains better or worse?
This is where the MRI evidence changes the picture. In the SURPASS-3 MRI analysis, 246 adults with type 2 diabetes took tirzepatide or insulin for 52 weeks. On tirzepatide:
- Thigh muscle volume fell by an average of 0.64 litres.
- Fat inside the muscle fell by 0.36 percentage points, a sign of better muscle quality.
- The muscle volume changes were similar to what population data from the UK Biobank would predict for the amount of weight lost.
The 2024 review read the MRI studies together and concluded that muscle changes with GLP-1 drugs “appear to be adaptive”: the reduction is “commensurate with what is expected given ageing, disease status, and weight loss achieved,” and better insulin sensitivity and less fat in the muscle likely mean “improved muscle quality, lowering the probability for loss in strength and function.” The same review adds a caution: older age and more severe disease “may influence the selection of appropriate candidates for these therapies due to risk of sarcopenia.”
Is muscle loss on Ozempic dangerous?
For most people with obesity, the evidence so far points to a proportionate, not a disproportionate, loss. The groups for whom it matters most are those who already have little muscle to spare: older adults, people with sarcopenia (see what is sarcopenia for the grip-strength and chair-stand cut-offs), and people with frailty. A 2024 JAMA viewpoint by researchers including Kevin Hall and Samuel Klein addressed exactly this question, “Is weight loss–induced muscle mass loss clinically relevant?”, which is itself a sign that the answer is not yet settled.
How to protect muscle while taking a GLP-1 drug
No large trial has yet tested a muscle-protection programme specifically alongside these drugs. The 2024 review notes that drugs designed to preserve muscle during GLP-1 treatment are in development. Until then, the interventions with the strongest evidence for muscle in general apply:
- Resistance training. It is the only treatment international sarcopenia guidelines strongly recommend. Our guide to building muscle after 60 covers how to start.
- Enough protein, which the same guidelines conditionally recommend; see how much protein older adults need for grams per kilogram.
- A baseline measure, such as grip strength or a five-times chair stand, before starting and again after a few months, so you know whether function, not only weight, is changing.
Frequently Asked Questions
Does Ozempic cause muscle loss?
Some, yes. Across 35 studies of GLP-1 drugs, a median 28.3% of the weight lost came from muscle-based measures. No study measured physical function, so whether that loss makes people weaker is not known.
Does Mounjaro cause more muscle loss than Ozempic?
Mounjaro (tirzepatide) produces more weight loss, so more total lean mass goes with it. The 2026 review could not pool the studies because their measurement methods differed, so a reliable head-to-head comparison of the muscle share by drug is not yet available.
Is the muscle loss permanent?
Resistance training improves lean mass, strength and physical function according to international sarcopenia guidelines, and protein is conditionally recommended alongside it. No long-term GLP-1 study has yet tracked muscle after stopping the drug and retraining.
Why does semaglutide cause muscle loss?
Mostly because large weight loss does: the body loses some lean tissue alongside fat, and diet-only weight loss does the same. In the SURPASS-3 MRI analysis, the muscle volume lost was similar to what population data predict for the amount of weight lost.
How much protein do I need on a GLP-1 drug?
There is no GLP-1-specific target. Use the general guidance for your age; our protein guide sets out grams per kilogram for older adults.
Who should be most careful?
Older adults and people who already have low muscle or sarcopenia. The 2024 review says older age and severity of disease may affect who is a suitable candidate because of the risk of sarcopenia.
The Bottom Line
GLP-1 drugs do take some muscle with the fat: a median 28% of the weight lost in 35 studies, more on DXA scans than on MRI. What the studies have not shown is a loss of strength or function, because none measured it, and MRI suggests the muscle that remains carries less fat. If you are older or already weak, measure your strength before you start, train against resistance, and keep protein up.
🔎 Our researched pick: Advanced Muscle Plus combines calcium HMB, dileucine and vitamin D3 in one daily regimen, for adults who want a supplement alongside resistance training and protein while losing weight. Our Advanced Muscle Plus review goes through the label ingredient by ingredient.
Affiliate link — if you buy through it we may earn a commission at no extra cost to you.
Sources
- Batsis JA, Gavras A, Gross DC, et al. Effect of Incretin-Based and Nonpharmacologic Weight Loss on Body Composition: A Systematic Review. Ann Intern Med, 2026;179(7):996-1013. PMID 41996180. 35 studies, median 26 weeks; median 28.3% (IQR 15.9-39.9%) of weight loss from muscle-based indices, 65% above ~25% benchmark; BIA/DXA ~29% (IQR 16.6-43.1%); CT/MRI ~25.3% (IQR 16.7-27.2%), two thirds above ~15% benchmark; “no study reported objective physical function outcomes”; heterogeneity “precluded meta-analysis.” Checked 5 October 2026.
- Neeland IJ, Linge J, Birkenfeld AL. Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies. Diabetes Obes Metab, 2024;26 Suppl 4:16-27. PMID 38937282. Lean mass 40-60% of weight lost in some studies, about 15% or less in others; lean mass “includes not only muscle but also organs, bone, fluids, and water in fat tissue”; MRI-based changes “appear to be adaptive”; older age and disease severity and risk of sarcopenia; muscle-preserving drugs in development. Checked 5 October 2026.
- Sattar N, Neeland IJ, Dahlqvist Leinhard O, et al. Tirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial. Lancet Diabetes Endocrinol, 2025;13(6):482-493. PMID 40318682. 246 with valid week-52 MRI; pooled tirzepatide muscle fat infiltration -0.36 percentage points, muscle volume -0.64 L; changes similar to UK Biobank population estimates for the weight lost. Checked 5 October 2026.
- Conte C, Hall KD, Klein S. Is Weight Loss-Induced Muscle Mass Loss Clinically Relevant? JAMA, 2024;332(1):9-10. PMID 38829659. Checked 5 October 2026.
- Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med, 2021;384(11):989-1002. PMID 33567185. Body weight -14.9% at week 68 vs -2.4% placebo. Checked 5 October 2026.
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med, 2022;387(3):205-216. PMID 35658024. Weight -15.0% at week 72 with 5 mg. Checked 5 October 2026.
- Dent E, Morley JE, Cruz-Jentoft AJ, et al. International Clinical Practice Guidelines for Sarcopenia (ICFSR). J Nutr Health Aging, 2018;22(10):1148-1161. PMID 30498820. Strong recommendation for resistance-based physical activity; conditional for protein. Checked 5 October 2026.