Written by Sven Wombwell
Published May 19, 2025 14 minutes read
Key Takeaways
- Fat and Lean Mass: Semaglutide can reduce both fat and lean mass, with studies showing more fat loss than lean mass loss.
- Lean Mass Is Not Just Muscle: It also includes water, organs and other non-fat tissues. A decrease does not show exactly how much muscle has been lost.
- Supporting Muscle Retention: Adequate protein and strength training can help preserve muscle during weight loss, but cannot guarantee complete muscle retention.
- Who Needs Extra Attention: Older adults and people with low muscle mass or strength need particular attention during treatment.
- TRT and Thyroid Care: These treatments may be appropriate for diagnosed testosterone deficiency or an underactive thyroid. They should not be added routinely to prevent muscle loss or accelerate weight loss.
- Track More Than Weight: Monitor strength and everyday function alongside your weight. Speak with your provider if your strength declines or you suspect muscle loss.
Semaglutide is now an established treatment for weight management, but the conversation has moved beyond how many pounds you can lose. For people considering treatment, another question matters: Can you lose fat while protecting your muscle and strength?
In the STEP 1 trial, adults with overweight or obesity without diabetes who received semaglutide 2.4 mg weekly alongside lifestyle changes lost an average of 14.9% of their body weight over 68 weeks, compared with 2.4% in the placebo group.
However, weight loss does not come entirely from fat. A body composition analysis of the trial found reductions in both fat and lean mass, although fat declined more. Lean mass includes muscle, but also water, organs and other tissues, so a decrease does not tell us exactly how much muscle someone has lost.
That distinction matters when asking whether semaglutide affects muscle growth. Losing weight, retaining muscle and building strength are different outcomes. Understanding how treatment affects each can help you look beyond the number on the scale.
This article explores what the research tells us about semaglutide and muscle loss, what remains uncertain and how to support muscle retention during weight loss.
What is Semaglutide?
Semaglutide is a prescription medication that mimics glucagon-like peptide-1 (GLP-1), a naturally occurring hormone involved in blood sugar control and appetite regulation. It belongs to a class of medications called GLP-1 receptor agonists.
When blood sugar is elevated, semaglutide helps the pancreas release insulin and reduces the release of glucagon, a hormone that signals the liver to release glucose. It also reduces appetite and helps you feel fuller, making it easier to eat less.
Semaglutide is the active ingredient in prescription medications such as Ozempic and Wegovy. FDA-approved indications vary by product and include type 2 diabetes, chronic weight management, and certain cardiovascular and other risk-reduction indications.
For adults, weight-management eligibility includes obesity or being overweight with at least one weight-related health condition. Semaglutide is available in injectable and oral forms, with approved uses and dosing depending on the product.
Although much of the weight lost with semaglutide comes from fat, some lean mass can also be lost. Lean mass includes muscle and other non-fat tissues, so these measurements do not directly show how much muscle has been lost.
Adequate protein, resistance training and ongoing provider guidance can help support muscle retention during treatment, but they do not guarantee that all muscle will be preserved.
Semaglutide and Muscle Mass
Semaglutide is prescribed in clinical settings due to its effectiveness in promoting weight loss. However, lean mass changes during treatment are influenced by factors including overall calorie intake, protein consumption and resistance training.
While semaglutide effectively reduces fat, its impact on muscle mass also depends on factors such as nutrition and exercise. In particular, rapid weight loss can reduce lean body mass, which includes muscle tissue. The extent to which these changes reflect weight loss itself versus other effects of semaglutide remains uncertain.
Without sufficient protein intake and proper exercise, the body may break down muscle tissue to meet its energy needs. A clinical study examined changes in body composition during semaglutide treatment alongside lifestyle changes, finding greater reductions in fat mass than skeletal muscle mass. However, it did not establish whether regular physical activity improved muscle preservation.
In this study involving 43 adults with obesity, participants underwent 24 weeks of treatment with semaglutide and lifestyle changes. The results indicated an average weight loss of 9.9 kg, or 11.2% of their body weight, with an estimated reduction in fat mass of 5.6 kg.
In contrast, estimated skeletal muscle mass decreased by 1.4 kg. This suggests that fat loss was more evident than muscle loss during the treatment. However, the study had no control group, so it could not determine the separate effects of semaglutide, calorie intake, protein consumption or exercise.
Fat loss and lean mass changes.
Weight loss often comes with a loss of both fat and lean mass. This isn't specific to semaglutide. It can occur across different weight loss approaches, including diet changes, surgical procedures and medications.
Clinical trials show that while both fat mass and lean mass can decrease during weight loss, the majority of weight lost with semaglutide is fat mass. Adequate protein intake and resistance training can help support muscle preservation.
In the STEP 1 body composition analysis, those who took a placebo lost less weight overall, with no major changes in body composition. The findings do not establish that the placebo group lost a higher proportion of lean mass than fat.
Keep in mind that muscle preservation still matters, and it shouldn't be ignored during treatment. Beyond body composition, semaglutide has shown additional benefits. Clinical trials have demonstrated improvements in blood sugar control, blood pressure and certain cardiometabolic markers.
Practical Tips for Maintaining Muscle Mass While on Semaglutide
As semaglutide supports weight loss, focusing on muscle preservation is important. The following strategies can help you retain muscle while achieving your weight loss goals.
Exercise
Maintaining muscle mass should be a priority as you use semaglutide for weight loss. One of the most effective ways to support this is through strength training.
Lifting weights stimulates muscle fibers and helps maintain skeletal muscle mass. Aim for two to three strength training sessions every week, working all major muscle groups and allowing recovery time between sessions for the same muscles. Resistance bands are another useful tool for preserving muscle while on semaglutide.
They offer an alternative to traditional weightlifting while engaging various muscle groups and supporting muscle growth when the resistance is sufficiently challenging. Resistance bands can be adapted to different abilities, but they are not automatically gentler on the joints or less strenuous than weights.
Cardio exercises also contribute to your overall fitness. Cardio supports weight loss, improves cardiovascular health and boosts endurance. However, it should complement strength training rather than replace it.
Consume a Balanced Diet
Eating the right way while using semaglutide makes a big difference in keeping your muscles strong. You can lose both fat and muscle during weight loss, but the right food choices can help your body hold onto muscle.
Protein supports muscle repair and growth by supplying the amino acids needed for muscle protein synthesis. Foods like chicken, fish, eggs, beans and yogurt are great places to start. Keep in mind that your calorie intake also matters. An excessive calorie deficit can increase the risk of muscle loss.
A more balanced approach helps you lose fat while supporting muscle retention. Eating enough protein and choosing a variety of nutrient-rich foods can support your energy needs and help your muscles recover after workouts. Eating more frequently is not essential for preserving muscle.
Lastly, consume sufficient vitamin D and calcium to support bone health while losing weight. Adult daily recommendations are generally 600-800 IU of vitamin D and 1,000-1,200 mg of calcium, depending on age and sex. These amounts refer to total intake from food and supplements combined, not an additional supplement dose.
Monitoring Progress
Stepping on the scale can be exciting or frustrating, but it rarely tells the whole story. When you're trying to lose weight, what you're losing matters: Is it fat, water or muscle?
That's where tracking the right measures can make a significant difference and help you make informed decisions. A body composition scale estimates fat and muscle rather than measuring them directly. Its readings can be inaccurate, so don't use it alone to determine whether you're losing muscle.
Additionally, you can take simple measurements with a tape measure around your waist, thighs or arms to see where your body is changing. These measurements add context but cannot distinguish fat loss from muscle loss. Tracking your strength and ability to perform everyday activities can also help. Muscles help you stay strong and support your metabolism. Losing muscle may affect strength and physical function, even if the scale shows progress.
That's why it's important to check in regularly. If your strength is declining or you suspect muscle loss, speak with your provider about your nutrition, rate of weight loss and strength training plan. Keep a simple log in an app or a notebook to stay on track. Over time, these regular check-ins can help you make informed changes and feel more in control of your progress.
Who Should Be Concerned About Muscle Loss While on Semaglutide?
Muscle loss is a possible concern for specific groups of people using semaglutide for weight management. Older people may be more vulnerable because of the natural reduction in strength and muscle mass that occurs with aging, particularly if they already have low muscle mass or strength.
A 2017 research review estimated that sarcopenia affects around 10% of community-dwelling adults aged 60 and older, although estimates vary depending on the population and diagnostic criteria. People with sarcopenia need particular attention to muscle preservation during weight loss.
Furthermore, athletes and bodybuilders should also pay close attention. Their performance depends partly on maintaining skeletal muscle mass. However, a decrease in lean mass does not necessarily mean a decrease in strength, stamina or muscle function.
Significant muscle loss may reduce training capacity. Also, anyone following a rapid weight loss plan may experience lean mass loss. Without sufficient protein intake and strength training, the risk of losing muscle alongside fat may increase. Loss of muscle and strength can affect mobility and physical function.
Can semaglutide be combined with TRT or thyroid treatment?
If you have low testosterone or an underactive thyroid, those conditions deserve attention alongside your weight loss goals. Your provider may recommend treating both conditions when each treatment is clinically appropriate.
Semaglutide and TRT
For men experiencing symptoms associated with low testosterone and whose laboratory results suggest suboptimal testosterone levels, testosterone replacement therapy (TRT) may help improve lean body mass. In a 56-week randomized trial involving 100 men with obesity and low testosterone, those receiving testosterone alongside a reduced-calorie diet had greater fat loss and better lean mass preservation than those receiving placebo. However, the study did not involve semaglutide, so it cannot establish the same benefit when the medications are combined.
TRT should be considered based on a diagnosis of testosterone deficiency, rather than automatically added to prevent muscle loss during semaglutide treatment. Adequate protein and resistance training remain important parts of your care.
Semaglutide and thyroid treatment
If you have an underactive thyroid, your provider may prescribe thyroid hormone replacement while you receive semaglutide. Thyroid medication treats the diagnosed condition; it should not be used to accelerate weight loss when thyroid function is normal.
Monitoring matters when treatments overlap. A study found that taking oral semaglutide with levothyroxine increased total thyroxine exposure, supporting the need to monitor thyroid levels when these medications are used together. This finding concerns oral semaglutide and does not establish the same interaction with injections.
Your provider can review your symptoms, labs and medical history to determine which treatments you need and monitor your response as your weight changes.
Conclusion
Semaglutide supports weight loss and metabolic health. As with other weight loss interventions, some lean mass reduction may occur, which is why resistance training and adequate protein intake are important. While semaglutide reduces appetite and helps regulate blood sugar, it does not guarantee muscle preservation.
A combination of exercise and nutrition can help preserve muscle during weight loss. So, if you're wondering, “Does semaglutide affect muscle growth?†the evidence is clearer about changes in muscle and lean mass during weight loss than about its direct effects on muscle growth. Nutrition, exercise and individual health all matter.
So, don't focus solely on the scale. Pay attention to changes in strength and physical function alongside weight and body composition. Before starting semaglutide, talk to your medical provider. They can offer advice on whether treatment is appropriate and how to support muscle retention.
Combine exercise, good nutrition and guidance from a qualified provider to support healthy, sustainable weight management. If you're considering semaglutide for weight management, a clinical assessment can help determine whether it is appropriate for your needs.
Start with a provider-led assessment to discuss your health goals and treatment options.
Male Excel providers develop individualized treatment plans based on your symptoms, labs and medical history.
References
Bergmann NC, Davies MJ, Lingvay I, Knop FK. Semaglutide for the treatment of overweight and obesity: A review. Diabetes, Obesity and Metabolism. 2023;25(1):18-35. https://pmc.ncbi.nlm.nih.gov/articles/PMC10092086/
Xiang J, Ding XY, Zhang W, et al. Clinical effectiveness of semaglutide on weight loss, body composition, and muscle strength in Chinese adults. European Review for Medical and Pharmacological Sciences. 2023;27(20):9908-9915. https://www.europeanreview.org/article/34169
Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine. 2021;384:989-1002. https://pubmed.ncbi.nlm.nih.gov/33567185/
Wilding JPH, Batterham RL, Calanna S, et al. Impact of Semaglutide on Body Composition in Adults With Overweight or Obesity: Exploratory Analysis of the STEP 1 Study. Journal of the Endocrine Society. 2021;5(Suppl 1)-A17. https://pmc.ncbi.nlm.nih.gov/articles/PMC8089287/
Shafiee G, Keshtkar A, Soltani A, et al. Prevalence of sarcopenia in the world: a systematic review and meta-analysis of general population studies. Journal of Diabetes & Metabolic Disorders. 2017;16:21. https://link.springer.com/article/10.1186/s40200-017-0302-x
American Society for Nutrition. Nutritional Priorities to Support GLP-1 Therapy for Obesity. 2025. https://nutrition.org/nutritional-priorities-to-support-glp-1-therapy-for-obesity/
National Institutes of Health, Office of Dietary Supplements. Vitamin D: Fact Sheet for Consumers. https://ods.od.nih.gov/factsheets/VitaminD-Consumer/
National Institutes of Health, Office of Dietary Supplements. Calcium: Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/Calcium-HealthProfessional/
Centers for Disease Control and Prevention. Adult Activity: An Overview. https://www.cdc.gov/physical-activity-basics/guidelines/adults.html
Accuracy of Smart Scales on Weight and Body Composition: Observational Study. JMIR mHealth and uHealth. 2021;9(4). https://mhealth.jmir.org/2021/4/e22487
Ng Tang Fui M, Prendergast LA, Dupuis P, et al. Effects of testosterone treatment on body fat and lean mass in obese men on a hypocaloric diet: a randomised controlled trial. BMC Medicine. 2016;14:153. https://pubmed.ncbi.nlm.nih.gov/27716209/
Hauge C, Breitschaft A, Hartoft-Nielsen ML, Jensen S, Bækdal TA. Effect of oral semaglutide on the pharmacokinetics of thyroxine after dosing of levothyroxine and the influence of co-administered tablets on the pharmacokinetics of oral semaglutide in healthy subjects: an open-label, one-sequence crossover, single-center, multiple-dose, two-part trial. Expert Opinion on Drug Metabolism & Toxicology. 2021;17(9):1139-1148. https://pubmed.ncbi.nlm.nih.gov/34289755/
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