Muscle loss in obese patients during- and post-GLP-1RA therapy

GLP1-RAs are widely used for weight management including weight loss and weight maintenance in obese patients. 

Obesity itself can lead to loss of muscle mass and function and obese individuals have a high prevalence of underlying chronic diseases that can negatively impact muscle metabolism¹.

In clinical studies of GLP-1Ras, weight reduction is primarily attributed to the loss of fat mass, however, studies have reported that losses of lean body mass can account for approximately 40% of the total weight reduction observed^2,3.

Whilst loss of body fat in an obese population is desirable, in view of the importance of LBM for the maintenance of overall health, the loss of LBM is an unwanted effect and a potentially serious concern, particularly for older or frail patients or patients with co-morbidities. Moreover, cessation of GLP-1RA therapy, can result in a rebound in body weight in favour of fat mass and at the expense of LBM, resulting in a less favourable muscle to fat ratio⁴.

¹Hong SH, Choi KM. (2020) Sarcopenic obesity, insulin resistance, and their implications in cardiovascular and metabolic consequences. Int J Mol Sci.;21(2):494.

²Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (2021) N Engl J Med.;384 (11):989–1002. doi: 10.1056/NEJMoa2032183

³McCrimmon RJ, Catarig A-M, Frias JP, et al.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 (2020) Diabetologia.;63:473–485. doi: 10.1007/ s00125-019-05065-8

⁴Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022; 24(8): 1553-1564. doi:10.1111/dom.14725