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
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.