Effects of Antidiabetic Drugs on Muscle Mass in Type 2 Diabetes Mellitus

Curr Diabetes Rev. 2021;17(3):293-303. doi: 10.2174/1573399816666200705210006.


Background: When considering the administration of glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, or metformin, it is important to understand their weight loss effect as well as the degree of muscle loss caused by each drug in clinical practice.

Objective: To comparatively examine the effects of GLP-1RAs and oral antidiabetic drugs, including SGLT2 inhibitors and metformin, on muscle mass and body weight in patients with type 2 diabetes via a network meta-analysis of randomized controlled trials.

Methods: We included randomized controlled trials evaluating the effects of antidiabetic drugs on muscle mass and body weight. Mean difference (MD) and 95% confidence intervals (CIs) were calculated using a random-effects network meta-analysis.

Results: Of the studies identified, 18 randomized controlled trials (1, 363 subjects) satisfied the eligibility criteria. In all studies, the effects of these drugs on fat-free mass (FFM) were evaluated. Therefore, FFM, which is used as an alternative index of muscle mass, was included in the study. Semaglutide (MD: -1.68, 95% CI: -2.84 to -0.52), dapagliflozin (-0.53, -0.93 to -0.13), and canagliflozin (-0.90, -1.73 to -0.07) showed a significant decrease in FFM compared with the placebo. Metformin did not show a significant decrease in FFM compared with the placebo. When compared with the placebo, semaglutide, dapagliflozin, ipragliflozin, and canagliflozin showed a significant weight loss.

Conclusion: Although semaglutide, dapaglifrozin, and canagliflozin have a large weight loss effect, it is important to pay attention to muscle loss because a decrease in FFM was observed.

Keywords: Antidiabetic drugs; body weight; glucagon-like peptide-1 receptor agonists; muscle mass; network meta-analysis; type 2 diabetes mellitus.

Publication types

  • Meta-Analysis

MeSH terms

  • Canagliflozin
  • Diabetes Mellitus, Type 2* / drug therapy
  • Humans
  • Hypoglycemic Agents
  • Muscles
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Treatment Outcome


  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • Canagliflozin