SGLT2 inhibitors reduce weight and fat mass in older adults with T2DM, with smaller muscle mass decline

Type 2 diabetes mellitus (T2DM) and obesity are growing global health concerns, particularly in older adults who are at higher risk of sarcopenia. While sodium-glucose cotransporter 2 (SGLT2) inhibitors show promise for glycemic control and weight loss, their effects on muscle health remain unclear. We examined the effects of SGLT2 inhibitors on body weight, fat mass, and muscle mass in T2DM patients. We systematically searched the PubMed, Embase, Scopus, and Cochrane databases for relevant randomized controlled trials (RCTs). Three reviewers screened the studies, and two extracted data and assessed their quality. R software was used to evaluate heterogeneity via Cochran's Q and I statistics. Eight RCTs (n = 541) were included. SGLT2 inhibitors significantly reduced body weight (standardized mean difference (SMD) = -0.85, p < 0.001; I = 0%) and fat mass (SMD = -0.53, p < 0.001; I = 51.1%). A small reduction in muscle mass was observed (SMD = -0.35, p < 0.001; I = 22.9%), though substantially smaller than fat loss. Subgroup analysis confirmed that fat mass was reduced with dapagliflozin/ipragliflozin (SMD = -0.67, p < 0.001; I = 26.4%) and empagliflozin (SMD = -0.53, p < 0.001; I = 66.4%). SGLT2 inhibitors effectively reduce body weight primarily through fat loss in older adults. Although muscle mass declined modestly, the predominance of fat loss suggests weight reduction occurs through favorable metabolic changes. Given the slight muscle mass changes and study heterogeneity, careful monitoring in older adults is warranted, and further studies in diverse populations are needed.