Pay attention to body composition when using weight-loss medication
Guest writer: Rob van Berkel, Research dietitian and writer on nutrition and health
Pay attention to body composition when using weight-loss medication
The use of weight-loss medication has increased significantly in recent times, both through prescription and other channels. These drugs are designed to accelerate and facilitate weight reduction — and they are indeed effective! However, they lead not only to the loss of fat mass but also to muscle mass, often to an excessive degree. Therefore, monitoring body composition is crucial to enable timely and targeted interventions.
What Do Weight-Loss Drugs Do?
The best-known weight-loss medications are the so-called GLP-1 receptor agonists (GLP-1 RAs), including liraglutide, semaglutide, and partly tirzepatide (which also contains a GIP-RA component). GLP-1 RAs mimic the natural hormone GLP-1 (glucagon-like peptide-1), promoting satiety and insulin secretion while suppressing glucagon release and delaying gastric emptying. Other drugs act on the appetite center in the brain (naltrexone/bupropion) or bind dietary fat in the intestine to prevent its absorption (orlistat). These mechanisms result in weight loss and improvements in cardiometabolic risk factors (Liu et al., 2024).
Clinical studies show that GLP-1 RAs can produce an average weight loss of 5.3% to 17.8% after 56 to 72 weeks compared with placebo (Mozaffarian et al., 2025). In real-world practice, results tend to be somewhat lower. After 60 weeks, semaglutide (2.4 mg/day) leads to an average weight loss of about 8% in people with diabetes and 11% in those without (Little et al., 2023).
The Importance of Muscle Mass
Muscles are essential for strength, performance, and metabolism (Harper et al., 2025). They take up glucose from the blood via insulin and consume more energy than fat tissue, even at rest. A loss of one kilogram of muscle mass lowers resting energy expenditure by 13 kcal per day, while fat loss decreases it by only 4.5 kcal (Wang et al., 2010). Active muscles can use up to 50–100 times more energy (Holloszy et al., 1984). Therefore, more muscle mass increases total energy expenditure, facilitating weight management.
Muscle mass also supports daily activities, aids recovery after illness or injury, and helps protect bones and joints. Low muscle mass is associated with a higher risk of type 2 diabetes, mortality, and reduced functionality in older age (Kim et al., 2024; Visser et al., 2025; Mechanick et al., 2025). Preserving muscle during weight loss is therefore essential.
The Effect of Weight-Loss Medication on Muscle Mass
In calorie-restricted diets, about 10–30% of total weight loss typically consists of fat-free mass (Chaston et al., 2007; Hall, 2007). This proportion is similar regardless of the total percentage of weight lost (Magkos et al., 2016). Fat-free mass serves as a proxy for muscle mass, as roughly half of it comprises muscle (alongside bone, connective tissue, organs, and water).
Studies with GLP-1 RAs show that the loss of fat-free mass can reach up to 45% after 36–72 weeks (Neeland et al., 2024). There is ongoing debate about whether this coincides with improved muscle quality due to reduced triglyceride levels within and between muscle cells. Preliminary evidence suggests that muscle strength may not decline, but more research is needed (Prado et al., 2024).
Because results vary greatly among individuals — with some losing only 10–25% of fat-free mass — individualised monitoring is highly recommended (Karakasis et al., 2025).
The Importance of Monitoring Body Composition
By monitoring body composition during the use of weight-loss medication, one can assess the ratio of fat to muscle mass and determine whether weight loss is occurring in a healthy and desirable manner.
Regular assessments can include bioelectrical impedance analysis (BIA), which measures changes in fat-free mass, fat mass, muscle mass, and total/intracellular/extracellular water. Based on these data, timely adjustments to diet or exercise programs can be made. For example, if muscle loss exceeds 25% (more than what typical calorie restriction would cause), increasing protein intake or strength training may be recommended. This approach promotes sustainable weight loss and long-term health.
How to Minimise Muscle Loss During Weight-Loss Medication
The reduction in skeletal muscle mass from weight loss is mainly due to increased muscle breakdown rather than decreased protein synthesis (Neeland et al., 2024). Strategies that stimulate muscle protein synthesis can therefore reduce the proportion of weight loss coming from muscle. Examples include a high-protein diet (1.2–1.6 g/kg/day) and physical exercise, especially resistance training (Cava et al., 2017; Chavez et al., 2024; Mozaffarian et al., 2024). New drugs are also being developed to minimise the loss of fat-free and muscle mass (Stefanakis et al., 2024; Harper et al., 2025).
Conclusion
Weight-loss medication can cause a greater reduction in fat-free mass (including muscle) than conventional dieting — in some cases up to 45% of total weight lost. Therefore, monitoring body composition is essential to detect and address excessive muscle loss early. Adequate protein intake and strength training are strongly recommended alongside medication to preserve muscle mass and support long-term metabolic health.
References
Cava E, Yeat NC, Mittendorfer B. Preserving Healthy Muscle during Weight Loss. Adv Nutr. 2017;8(3):511-519. Published 2017 May 15.
Chaston TB, Dixon JB, O'Brien PE. Changes in fat-free mass during significant weight loss: a systematic review. Int J Obes (Lond) 2007; 31(5): 743-50.
Chavez AM, Carrasco Barria R, León-Sanz M. Nutrition support whilst on glucagon-like peptide-1 based therapy. Is it necessary?. Curr Opin Clin Nutr Metab Care. 2025;28(4):351-357.
Conte C, Hall KD, Klein S. Is Weight Loss-Induced Muscle Mass Loss Clinically Relevant?. JAMA. 2024;332(1):9-10.
Hall KD. Body fat and fat-free mass inter-relationships: Forbes’s theory revisited. Br J Nutr. 2007;97(6):1059-1063.
Harper ME, Dent RRM, McPherson R. High-Quality Weight Loss in Obesity: Importance of Skeletal Muscle. Diabetes. Published online July 8, 2025.
Holloszy JO, Coyle EF. Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. J Appl Physiol Respir Environ Exerc Physiol. 1984;56(4):831-838.
Karakasis P, Patoulias D, Fragakis N, Mantzoros CS. Effect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition: Systematic review and network meta-analysis. Metabolism. 2025;164:156113.
Kim D, Lee J, Park R, Oh C-M, Moon S. Association of low muscle mass and obesity with increased all-cause and cardiovascular disease mortality in US adults. J Cachexia Sarcopenia Muscle 2024;15:240–254.
Little D, Deckert J, Bartelt K, Ganesh M, Stamp T. Weight change with semaglutide, Epic, Research, April 25, 2023.
Liu L, Li Z, Ye W, et al. Safety and effects of anti-obesity medications on weight loss, cardiometabolic, and psychological outcomes in people living with overweight or obesity: a systematic review and meta-analysis. EClinicalMedicine. 2024;79:103020. Published 2024 Dec 27.
Magkos F, Fraterrigo G, Yoshino J, et al. Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity. Cell Metab. 2016;23 (4):591-601.
Mechanick JI, Butsch WS, Christensen SM, et al. Strategies for minimizing muscle loss during use of incretin-mimetic drugs for treatment of obesity. Obes Rev. 2025;26(1):e13841.
Mozaffarian D, Agarwal M, Aggarwal M, et al. Nutritional priorities to support GLP-1 therapy for obesity: A joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society. Obesity (Silver Spring). 2025;33(8):1475-1503.
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.
Prado CM, Phillips SM, Gonzalez MC, Heymsfield SB. Muscle matters: the effects of medically induced weight loss on skeletal muscle. Lancet Diabetes Endocrinol. 2024 Nov;12(11):785-787.
Stefanakis K, Kokkorakis M, Mantzoros CS. The impact of weight loss on fat-free mass, muscle, bone and hematopoiesis health: Implications for emerging pharmacotherapies aiming at fat reduction and lean mass preservation. Metabolism. 2024;161:156057.
Visser M, Sääksjärvi K, Burchell GL, Schaap LA. The association between muscle mass and change in physical functioning in older adults: a systematic review and meta-analysis of prospective studies. Eur Geriatr Med. Published online May 23, 2025.
Wang Z, Ying Z, Bosy-Westphal A, Zhang J, Schautz B, Later W, Heymsfield SB, Müller MJ. Specific metabolic rates of major organs and tissues across adulthood: evaluation by mechanistic model of resting energy expenditure. Am J Clin Nutr. 2010 Dec;92(6):1369-77.
Zurlo F, Larson K, Bogardus C, Ravussin E. Skeletal muscle metabolism is a major determinant of resting energy expenditure. J Clin Invest. 1990;86(5):1423-1427.
