Muscle Loss & Drugs Like Ozempic – What is the Evidence?

Metabolic Health, Weight Loss / By

Importance of Muscle in Weight Loss

Muscle mass plays a pivotal role in our health and overall resillience (Kim & Kim, 2020). Losing muscle mass, also known as sarcopenia, poses several risks, including metabolic diseases, decreased survival during illness, frailty, and overall bad health outcomes (Blundell et al., 2017). Moreover, the loss of muscle during a weight loss program, if not managed properly, can lead to worsened body composition if the lost weight is regained (Kim & Kim, 2020).

Muscle Loss During Weight Loss

While it would be ideal to lose fat and gain muscle, this is not the norm for many individuals during weight loss (Kim & Kim, 2020). Instead, most people tend to lose both fat and muscle mass during weight loss (Srikanthan & Karlamangla, 2014). Hence, the core question: do GLP-1 receptor agonists exacerbate muscle wasting beyond what is observed in conventional weight loss programs (Ashtary-Larky et al., 2020)?

What Affects Muscle Mass During Weight Loss?

The extent of muscle loss during weight reduction hinges on various factors, including:

  • Protein Intake: Maintaining adequate protein intake can help preserve muscle mass during weight loss (Pasiakos et al., 2013).
  • Strength Training: Incorporating resistance training into a weight loss program has been shown to mitigate muscle wasting and improve strength (Villareal et al., 2011).
  • Age: Age plays a role in the degree of muscle loss, with older adults facing greater challenges (Srikanthan & Karlamangla, 2014).
  • Starting Body Weight and Composition: Baseline factors also influence muscle mass changes during weight loss (Ashtary-Larky et al., 2020).

Clinical Trials

While the gold standard for investigating the effects of GLP-1 receptor agonists on muscle tissue would be large randomized clinical trials, these studies often report only changes in body weight, neglecting body composition or strength changes (Wilding et al., 2021).

GLP-1 Studies

However, some data do exist that can guide us. For instance, in the STEP 1 trial involving semaglutide for weight loss, lean mass accounted for approximately 38% of total weight loss at 68 weeks (Wilding et al., 2021). However, the trial’s design omitted a robust resistance or strength training program, with participants encouraged to engage in “walking” as their primary physical activity (McCrimmon et al., 2020). Similar findings were observed in the SUSTAIN 8 trial, where semaglutide led to a loss of about 40% of total weight from lean mass at 52 weeks (McCrimmon et al., 2020). Unfortunately, this study also lacked a resistance training component.

Moreover, a smaller randomized crossover trial with semaglutide reported a lean mass loss of approximately 31% over 12 weeks (Kim & Kim, 2020). These studies collectively suggest that GLP-1 receptor agonists can lead to substantial lean mass loss, even though they may improve the fat-to-lean mass ratio (Kim & Kim, 2020).

Combined GLP-1/GIP Studies

At the time of this writing, data on combined GLP-1/GIP receptor agonists do not offer a more promising outlook for muscle preservation, as they have also been associated with substantial lean mass losses (Jastreboff et al., 2022).

Challenges in Study Design

While some studies claim to have preserved muscle mass or strength with GLP-1 receptor agonists, many rely on less reliable methods for measuring body composition (Kim & Kim, 2020). These findings warrant caution when assessing the impact of these drugs on muscle health.

Preserving Muscle During Weight Loss

Important: This content is medical advice and do not constitute the practice of medicine. These principles are based on general scientific literature and are not meant to be individualized or personalized. Always ask your doctor before making any health changes.

General Principles

In the absence of specific studies on preventing muscle loss with GLP-1 receptor agonists, it is prudent to consider general principles established in the weight loss literature (Cava et al., 2017).

  1. Protein Intake: Maintaining adequate protein intake is crucial. The recommended daily allowance (RDA) suggests 0.8 g/kg/day or approximately 0.36 g/lb/day for adults (Kim & Kim, 2020). However, individual protein requirements can vary based on factors such as age, activity level, and health status.
  2. Strength Training: Incorporating resistance or strength training exercises into a weight loss program has consistently shown to mitigate muscle loss and improve overall body composition (Villareal et al., 2011).
  3. Monitoring: Regularly assessing body composition, using reliable techniques like DXA scans or bioimpedance, can help individuals track changes over time and adjust their strategies accordingly (Kim & Kim, 2020).

Summary

In conclusion, the evidence surrounding GLP-1 receptor agonists like semaglutide and combined GLP-1/GIP receptor agonists raises concerns about the potential for muscle loss during weight loss programs. While these medications offer promising benefits for weight reduction and metabolic health improvement, it is essential to consider the potential trade-offs, including the loss of valuable muscle mass and strength. Therefore, patients and healthcare providers must weigh these risks and benefits carefully when deciding on the most suitable weight loss strategy (Blundell et al., 2017). Further research is needed to provide more definitive answers regarding the extent muscle changes that occur while on GLP-1 receptor or GLP-1/GIP receptor agonists, as well as muscle preservation on these drugs.

Disclaimer: The content of this article is for general information purposes only and does not constitute the practice of medicine or any other healthcare professional services. No doctor-patient relationship is formed. The content of this video should not take precedence over information provided to you by your healthcare provider or official public health sources. Please visit https://nicksterling.com/terms for full Terms of Use.

References

  1. Kim G, Kim JH. Impact of Skeletal Muscle Mass on Metabolic Health. Endocrinol Metab (Seoul). 2020 Mar;35(1):1-6.
  2. Srikanthan, Preethi, and Arun S. Karlamangla. 2014. “Muscle Mass Index as a Predictor of Longevity in Older Adults.” The American Journal of Medicine 127 (6): 547–53.
  3. Ashtary-Larky, Damoon, Reza Bagheri, Amir Abbasnezhad, Grant M. Tinsley, Meysam Alipour, and Alexei Wong. 2020. “Effects of Gradual Weight Loss v. Rapid Weight Loss on Body Composition and RMR: A Systematic Review and Meta-Analysis.” The British Journal of Nutrition 124 (11): 1121–32.
  4. Cava, Edda, Nai Chien Yeat, and Bettina Mittendorfer. 2017. “Preserving Healthy Muscle during Weight Loss.” Advances in Nutrition 8 (3): 511–19.
  5. Wilding, John P. H., Rachel L. Batterham, Salvatore Calanna, Melanie Davies, Luc F. Van Gaal, Ildiko Lingvay, Barbara M. McGowan, et al. 2021. “Once-Weekly Semaglutide in Adults with Overweight or Obesity.” The New England Journal of Medicine 384 (11): 989–1002.
  6. McCrimmon, Rory J., Andrei-Mircea Catarig, Juan P. Frias, Nanna L. Lausvig, Carel W. le Roux, Desirée Thielke, and Ildiko Lingvay. 2020. “Effects of Once-Weekly Semaglutide vs Once-Daily Canagliflozin on Body Composition in Type 2 Diabetes: A Substudy of the SUSTAIN 8 Randomised Controlled Clinical Trial.” Diabetologia 63 (3): 473–85.
  7. Blundell, John, Graham Finlayson, Mads Axelsen, Anne Flint, Catherine Gibbons, Trine Kvist, and Julie B. Hjerpsted. 2017. “Effects of Once-Weekly Semaglutide on Appetite, Energy Intake, Control of Eating, Food Preference and Body Weight in Subjects with Obesity.” Diabetes, Obesity & Metabolism 19 (9): 1242–51.
  8. Jastreboff, Ania M., Louis J. Aronne, Nadia N. Ahmad, Sean Wharton, Lisa Connery, Breno Alves, Arihiro Kiyosue, et al. 2022. “Tirzepatide Once Weekly for the Treatment of Obesity.” The New England Journal of Medicine 387 (3): 205–16.
  9. Volpe, Sara, Giuseppe Lisco, Davide Racaniello, Margherita Fanelli, Valentina Colaianni, Alfredo Vozza, Vincenzo Triggiani, et al. 2022. “Once-Weekly Semaglutide Induces an Early Improvement in Body Composition in Patients with Type 2 Diabetes: A 26-Week Prospective Real-Life Study.” Nutrients 14 (12): 2414.
  10. Volpe, Sara, Giuseppe Lisco, Margherita Fanelli, Davide Racaniello, Valentina Colaianni, Valentina Lavarra, Domenico Triggiani, et al. 2023. “Oral Semaglutide Improves Body Composition and Preserves Lean Mass in Patients with Type 2 Diabetes: A 26-Week Prospective Real-Life Study.” Frontiers in Endocrinology 14 (September): 1240263.
  11. Uchiyama, Syutaro, Yukiyoshi Sada, Syohei Mihara, Yosuke Sasaki, Masakatsu Sone, and Yasushi Tanaka. 2023. “Oral Semaglutide Induces Loss of Body Fat Mass Without Affecting Muscle Mass in Patients With Type 2 Diabetes.” Journal of Clinical Medicine Research 15 (7): 377–83.
  12. Pasiakos, Stefan M., Jay J. Cao, Lee M. Margolis, Edward R. Sauter, Leah D. Whigham, James P. McClung, Jennifer C. Rood, John W. Carbone, Gerald F. Combs Jr, and Andrew J. Young. 2013. “Effects of High-Protein Diets on Fat-Free Mass and Muscle Protein Synthesis Following Weight Loss: A Randomized Controlled Trial.” The FASEB Journal 27 (9): 3837–47.
  13. Verreijen, Amely M., Sjors Verlaan, Mariëlle F. Engberink, Sophie Swinkels, Johan de Vogel-van den Bosch, and Peter J. M. Weijs. 2014. “A High Whey Protein-, Leucine-, and Vitamin D-Enriched Supplement Preserves Muscle Mass during Intentional Weight Loss in Obese Older Adults: A Double-Blind Randomized Controlled Trial.” The American Journal of Clinical Nutrition 101 (2): 279–86.
  14. Villareal, Dennis T., Suresh Chode, Nehu Parimi, David R. Sinacore, Tiffany Hilton, Reina Armamento-Villareal, Nicola Napoli, Clifford Qualls, and Krupa Shah. 2011. “Weight Loss, Exercise, or Both and Physical Function in Obese Older Adults.” The New England Journal of Medicine 364 (13): 1218–29.