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GLP-1s, muscle and bone: what the trials measured

Updated Sep 27, 2026. Numbers in brackets link to the source each fact comes from.

GLP-1 medicines take off some muscle along with fat, and the FDA labels for Zepbound, Wegovy and Foundayo all say the same thing about it: people lost more fat than lean mass [1] [2] [3]. How much lean mass, and whether it matters for strength or bones, comes from smaller studies. This page reports what they measured and what NIH and professional groups advise; the decisions belong with your prescriber.

What the trial scans found

Tirzepatide (Zepbound, Mounjaro). In the main Zepbound weight trial, 160 participants had DXA body scans, which split weight into fat mass and lean mass (which includes muscle), at the start and at week 72 [4]. On tirzepatide, body weight fell 21.3%, fat mass 33.9% and lean mass 10.9%; on placebo the figures were 5.3%, 8.2% and 2.6% [5]. In both groups, about 75% of the weight lost was fat and about 25% was lean mass [5]. In other words, the drug did not change the share of lean mass lost; it increased the total amount of weight lost.

Semaglutide (Wegovy, Ozempic). A 2026 analysis of a Wegovy trial used MRI scans in only 55 participants, most of them on the 7.2 mg dose [6]. Its authors reported reductions in fat volume, muscle volume and fat inside the thigh muscle, while people could still do as many sit-to-stand repeats [7]. With only 6 people in the placebo group, a study this small can show a direction but not a precise size [6].

Across the drug class. A 2026 review pooled 60 studies with more than 1.2 million people [8]. It found GLP-1 medicines were linked to lower lean mass, but rated the certainty of that evidence as low, said the change appeared largely related to weight loss, and said it is still uncertain whether it affects strength or physical performance [10].

What about bone?

None of the GLP-1 labels we read lists bone loss or fractures as a side effect. The same 2026 review found no effect on bone density or fractures once the analysis adjusted for other factors [9]. A joint advisory from four obesity and nutrition groups (the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association and The Obesity Society) still lists muscle and bone loss among the challenges of GLP-1 treatment [11]. So one large review found no bone effect, while the advisory still counts bone loss as something to manage.

What professional groups and NIH advise

Before and during treatment. The joint advisory recommends checking muscle strength, function and body composition as part of the exam before starting [12]. During treatment, it names resistance training and an appropriate diet as the way to help preserve muscle and bone [13].

Strength training. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) says regular muscle-strengthening activity may help maintain muscle as you lose weight and help prevent bone loss as you age [14]. It suggests at least 2 days a week, with a rest day before working the same muscles again [15]. If you are new to it, NIDDK suggests starting with 1 day a week at light or moderate effort and building up [16].

Aerobic activity. NIDDK’s general advice is at least 150 minutes a week of moderate activity such as brisk walking [17]. In the Zepbound withdrawal trial, the lifestyle program recommended at least 150 minutes a week of activity alongside a reduced-calorie diet [20].

Protein. MedlinePlus says protein should make up 10% to 35% of daily calories for healthy adults [18]. It also says you can get enough protein without eating animal products [19]. The joint advisory lists nutrient shortfalls from eating fewer calories among the challenges of treatment [11], which is a reason to talk with your prescriber or a registered dietitian about your meals.

The joint advisory also talks in grams per kilogram of body weight. It gives 0.8 g/kg a day as the recommended amount for adults in general [22], and notes that higher targets of 1.2 to 1.6 g/kg a day have been proposed while someone is actively losing weight [23]. It adds a caveat: for people with obesity, it is not settled whether to count by actual weight, an adjusted weight or fat-free mass, and using actual weight can overstate how much protein is needed [24]. These are figures the advisory reports for clinicians, not a personal target. Ask your prescriber or a registered dietitian what fits you.

Who should ask about a scan

Your prescriber can tell you whether a body composition or bone density test makes sense for you. The joint advisory’s call for a body composition assessment [12] is guidance written for practicing clinicians [21], not a rule that every patient needs a scan.

Sources

  1. Tirzepatide lowers body weight with greater fat mass loss than lean mass loss. dailymed.nlm.nih.gov, read Sep 27, 2026.
  2. Semaglutide lowers body weight with greater fat mass loss than lean mass loss. dailymed.nlm.nih.gov, read Sep 27, 2026.
  3. FOUNDAYO reduces body weight, with greater fat mass loss than lean mass loss. dailymed.nlm.nih.gov, read Sep 27, 2026.
  4. Substudy participants (n = 160 of the 2539 in SURMOUNT-1) underwent dual-energy X-ray absorptiometry (DXA) at baseline and Week 72. pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  5. The change in body weight, fat mass and lean mass from baseline to Week 72 was -21.3%, -33.9% and -10.9% with tirzepatide and -5.3%, -8.2% and -2.6% with placebo, respectively (p < 0.001 for all comparisons). Of the body weight lost, approximately 75% was fat mass and 25% was lean mass for both tirzepatide and placebo. pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  6. Of 1407 participants, 55 with a valid baseline scan were included (semaglutide 7.2 mg, n = 43, 2.4 mg, n = 6 [pooled semaglutide group, n = 49]; placebo, n = 6). pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  7. Semaglutide plus lifestyle intervention was associated with reductions in adipose tissue volume, skeletal muscle volume and skeletal muscle fat infiltration, with a preserved number of sit-to-stand repetitions. pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  8. From 1148 potentially relevant references, 60 articles (46 RCTs, 13 RWE studies and 1 pharmacovigilance study, comprising 1,250,717 individuals) met our inclusion criteria. pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  9. No effect on bone outcomes (i.e., bone mineral density [all sites] and fractures [all sites]) were observed when the meta-analytical models included the most adjusted effect size. pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  10. While no significant effects were observed on bone- or joint-related outcomes, GLP-1 RAs were associated with reductions in lean body mass/fat-free mass, although the certainty of evidence was low and these changes appeared largely related to weight loss. Whether these changes translate into clinically meaningful impairments in muscle function or physical performance remains uncertain. pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  11. Challenges include side effects, especially gastrointestinal; nutritional deficiencies due to calorie reduction; muscle and bone loss; low long-term adherence with subsequent weight regain; and high costs with resulting low cost-effectiveness. pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  12. (c) comprehensive exam including muscle strength, function, and body composition assessment pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  13. During GLP-1 use, nutritional and medical management of gastrointestinal side effects is critical, as is navigating altered dietary preferences and intakes, preventing nutrient deficiencies, preserving muscle and bone mass through resistance training and appropriate diet, and complementary lifestyle interventions. pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  14. Doing regular activities to strengthen your muscles may help you increase bone strength and prevent bone loss as you age maintain muscle mass and prevent muscle loss as you age or as you lose weight niddk.nih.gov, read Sep 27, 2026.
  15. You should also aim for at least 2 days a week of muscle-strengthening activities. To avoid injury, allow at least 1 day of rest for your muscles to recover and rebuild before working the same muscle groups again. niddk.nih.gov, read Sep 27, 2026.
  16. Be sure to increase your muscle-strengthening activities gradually. Start out 1 day a week at a light or moderate intensity. Over time, increase to 2 days a week, and then possibly to more than 2 days. niddk.nih.gov, read Sep 27, 2026.
  17. Experts recommend at least 150 minutes a week (a total of 2 ½ hours) of moderate-intensity aerobic activity. niddk.nih.gov, read Sep 27, 2026.
  18. The daily recommended intake of protein for healthy adults is 10% to 35% of your total calorie needs. medlineplus.gov, read Sep 27, 2026.
  19. You do not need to eat animal products to get all the protein you need in your diet. medlineplus.gov, read Sep 27, 2026.
  20. All patients received a standard lifestyle intervention which included instruction on a reduced-calorie diet (approximately 500 kcal/day deficit) and increased physical activity counseling (recommended minimum of 150 min/week) dailymed.nlm.nih.gov, read Sep 27, 2026.
  21. We aimed to identify pragmatic priorities for nutrition and other lifestyle interventions relevant to GLP-1 treatment of obesity for the practicing clinician. pubmed.ncbi.nlm.nih.gov, read Sep 27, 2026.
  22. For the general adult population, the recommended daily allowance for protein is 0.8 g/kg/d pmc.ncbi.nlm.nih.gov, read Sep 28, 2026.
  23. Higher targets, such as 1.2–1.6 g/kg/d, have also been proposed during active weight reduction pmc.ncbi.nlm.nih.gov, read Sep 28, 2026.
  24. For individuals with obesity, it is unclear whether these goals should be based on actual body weight, corrected (adjusted or ideal) body weight, or fat-free mass, as the use of actual weight can significantly overestimate protein requirements pmc.ncbi.nlm.nih.gov, read Sep 28, 2026.

This page reports what official sources say; it is not medical advice. Medical disclaimer.