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 metaanalysis.
Results: Of the studies identified, 18 randomized controlled trials (1, 363 subjects) satisfied the eligibility criteria. In all
studies, 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.