GLP-1 Therapies and Risk of Muscle Loss

Glucagon-like peptide-1 (GLP-1) medications have increasingly been prescribed to treat cardiometabolic conditions such as obesity, diabetes, and cardiovascular diseases—Yeo et al (2024) conducted a nationwide analysis on the usage of GLP-1’s in patients without diabetes and observed a 700% (from 21,000 in 2019 to 174,000 in 2023) increase between the years 2019-2023. And while these treatments have been shown to be effective in supporting significant amounts of weight loss and improvements in health status, there also may be a risk of losing skeletal muscle mass. In this month’s newsletter, Clinical Research Associate Joseph Bonner will briefly review how this can happen and the importance of tracking skeletal muscle mass during weight loss.

How Do GLP-1 Treatments Work?

GLP-1 is an incretin hormone produced by the gut that has multiple effects on metabolism and weight regulation. GLP-1 binds to receptors of pancreatic beta cells that increase insulin sensitivity—which can increase glucose uptake and lower blood sugar levels. These effects can improve glucose tolerance, which is especially meaningful in Type 2 Diabetes and Metabolic Syndrome. Additionally, it can slow down gastric emptying, which can increase feelings of satiety and reduce caloric intake. Regarding hunger cues, it can also act on the central nervous system to further suppress appetite and increase satiety signals. However, GLP-1 as a hormone is rapidly broken down in the body, limiting the duration that it can induce these effects. GLP-1 receptor agonist medications mimic these effects while lasting for significantly longer periods of time. This means that patients utilizing these drugs can consistently decrease their appetite and caloric intake, which can lead to significant amounts of weight loss.

Efficacy of Weight-loss

A recent systematic review and a meta-analysis by Wong et al (2025) found that GLP-1 receptor agonists induced an additional 4.45 kilogram of weight loss over placebo based on 47 randomized control trials with a cohort of 23,244 patients. For studies that were over one year in duration, this increased to 8 kilograms. Similar findings have been observed Pan et al (2024), which noted significant differences between multiple GLP-1 medications compared with placebo for achieving greater than 5%, 10%, and even 15% weight loss.

Source: Wong et al (2025) Diabetes Care. 2025;48(2):292-300. doi:10.2337/dc24-1678

Risk of Losing Fat-Free Mass & Skeletal Muscle Mass

Inducing weight loss can also increase the likelihood of losing fat free mass and skeletal muscle mass. Broadly speaking, fat free mass refers to “The estimated mass of all nonfat molecules in the body, regardless of where they occur.” (Tinsley & Heymsfield, 2024). Skeletal muscle mass can be defined as “The estimated mass of all anatomically defined skeletal muscles in the body.” (Tinsley & Heymsfield, 2024). It’s important to note that there are several factors impacting the proportion of fat free mass loss that can occur during a weight loss period. A comprehensive review by Dr. Steven Heymsfield et al noted that “…many factors can influence individual changes in FFM relative to weight loss—including dietary intake, physical activity, aging, the metabolic and hormonal state—and individual factors like adiposity, race, and sex.” Tracking body composition changes during GLP-1 receptor agonist induced weight loss has become increasingly needed in the context of muscle tissue loss. Several researchers have used InBody technology as a useful tool in this regard.

Ozeki et al (2022) found that “GLP1-RA semaglutide effectively reduces body adiposity while maintaining the skeletal muscle mass in obese Type 2 Diabetic patients.” Xiang et al (2023) had similar findings, “…semaglutide can reduce the weight and fat of obese patients while effectively maintaining muscle mass and muscle strength.” Chen et al (2023) conducted a 3-month intervention using dulaglutide in patients with Type 2 Diabetes, noting “, dulaglutide intervention does not cause muscle and bone mass loss while inducing weight loss, and % change in body fat was independently associated with improved glucose control during dulaglutide therapy.”

For more information on skeletal muscle mass, body composition, and related topics, subscribe to our newsletter and connect with our medical & research team today.

References

1. Wang, J. Y., Wang, Q. W., Yang, X. Y., Yang, W., Li, D. R., Jin, J. Y., … & Zhang, X. F. (2023). GLP− 1 receptor agonists for the treatment of obesity: role as a promising approach. Frontiers in endocrinology, 14, 1085799.
2. Yeo YH Rezaie A Hsieh TY Hu X Gaddam S Ma KS Gastrointestinal Motility and Metabolic Pharmacoepidemiology Group. Shifting trends in the indication of glucagon-like peptide-1 receptor agonist prescriptions: a nationwide analysis. Ann Intern Med 2024. 10.7326/M24-0019.  39038291
3. Baggio, L. L., & Drucker, D. J. (2007). Biology of incretins: GLP-1 and GIP. Gastroenterology, 132(6), 2131-2157.
4. Wong, H. J., Sim, B., Teo, Y. H., Teo, Y. N., Chan, M. Y., Yeo, L. L., … & Sia, C. H. (2025). Efficacy of GLP-1 receptor agonists on weight loss, BMI, and waist circumference for patients with obesity or overweight: a systematic review, meta-analysis, and meta-regression of 47 randomized controlled trials. Diabetes Care, 48(2), 292-300.
5. Pan, X. H., Tan, B., Chin, Y. H., Lee, E. C. Z., Kong, G., Chong, B., … & Chan, M. Y. (2024). Efficacy and safety of tirzepatide, GLP‐1 receptor agonists, and other weight loss drugs in overweight and obesity: a network meta‐analysis. Obesity, 32(5), 840-856.
6. Grant M Tinsley, Steven B Heymsfield, Fundamental Body Composition Principles Provide Context for Fat-Free and Skeletal Muscle Loss With GLP-1 RA Treatments, Journal of the Endocrine Society, Volume 8, Issue 11, November 2024, bvae164, https://doi.org/10.1210/jendso/bvae164
7. Heymsfield   SB, Gonzalez   MCC, Shen   W, Redman   L, Thomas   D. Weight loss composition is one-fourth fat-free mass: a critical review and critique of this widely cited rule. Obes Rev. 2014;15(4):310‐321.
8. Ozeki, Y., Masaki, T., Kamata, A., Miyamoto, S., Yoshida, Y., Okamoto, M., Gotoh, K., & Shibata, H. (2022). The Effectiveness of GLP-1 Receptor Agonist Semaglutide on Body Composition in Elderly Obese Diabetic Patients: A Pilot Study. Medicines, 9(9), 47. https://doi.org/10.3390/medicines9090047
9. Xiang, J., Ding, X. Y., Zhang, W., Zhang, J., Zhang, Y. S., Li, Z. M., … & Liang, Y. Z. (2023). Clinical effectiveness of semaglutide on weight loss, body composition, and muscle strength in Chinese adults. European Review for Medical & Pharmacological Sciences, 27(20).
10. Chen, S., Wang, X., Jin, Y., Chen, X., Song, Q., Wei, G., & Li, L. (2024). Assessment of changes in body composition after 3 months of dulaglutide treatment. Diabetes, Metabolic Syndrome and Obesity, 1301-1308.