Xiaona Li, Yanrui Zhang, Luxun Wang, Yuanyuan Zhao
In adults with T2DM, SGLT2 inhibitors reduce adiposity without clear evidence of clinically meaningful reductions in SMM. However, because muscle strength and physical performance outcomes were rarely reported, the current evidence is insufficient to determine the impact of SGLT2 inhibitors on sarcopenia risk. Findings for LM should be interpreted cautiously, as LM does not directly reflect muscle mass.
BACKGROUND: Although Sodium-glucose transporter 2 (SGLT2) inhibitors provide substantial cardiovascular and renal benefits in type 2 diabetes mellitus (T2DM), their effects on sarcopenia-related body composition outcomes remain uncertain.
METHODS: Eight databases were searched for randomized controlled trials (RCTs) enrolling adults with T2DM that compared SGLT2 inhibitors with placebo or other glucose-lowering therapies, with a minimum follow-up of 12 weeks. A frequentist random-effects network meta-analysis was conducted. Primary outcomes were skeletal muscle mass (SMM) and lean mass (LM). Secondary outcomes included fat mass (FM), body fat percentage (PBF), visceral and subcutaneous fat, anthropometric measures, and safety outcomes.
RESULTS: Thirty-three RCTs involving 5,399 participants were included. No SGLT2 inhibitor significantly reduced SMM compared with placebo (all 95% confidence intervals crossed zero). For LM, empagliflozin (mean difference [MD] -1.22 kg, 95% CI -1.71 to -0.72), ipragliflozin (MD -0.99 kg, 95% CI -1.45 to -0.54), and canagliflozin (MD -0.80 kg, 95% CI -1.39 to -0.21) were associated with modest reductions in LM compared with placebo, whereas dapagliflozin and tofogliflozin showed neutral effects. In contrast, SGLT2 inhibitors consistently reduced FM (e.g., dapagliflozin MD -1.75 kg, 95% CI -2.63 to -0.87), PBF, visceral and subcutaneous fat, body weight (BW), body mass index (BMI), and waist circumference (WC). Safety analyses were limited by sparse networks and should be interpreted cautiously.
CONCLUSION: In adults with T2DM, SGLT2 inhibitors reduce adiposity without clear evidence of clinically meaningful reductions in SMM. However, because muscle strength and physical performance outcomes were rarely reported, the current evidence is insufficient to determine the impact of SGLT2 inhibitors on sarcopenia risk. Findings for LM should be interpreted cautiously, as LM does not directly reflect muscle mass.
SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420261379719.