Comparative effects of enavogliflozin versus dapagliflozin on adipokines in patients with type 2 diabetes mellitus: a pooled analysis of two randomized controlled trials

Abstract Background Although SGLT2 inhibitor–induced amelioration of adipokines is known to confer cardiometabolic benefits, it remains unclear whether individual SGLT2 inhibitors differ in their effects on adipokine regulation. In this study, we compared the effects of enavogliflozin and dapagliflozin on adipokine levels in patients with type 2 diabetes mellitus (T2DM). Methods This study is a pooled secondary analysis of two randomized, active-controlled, phase III trials comparing enavogliflozin 0.3 mg ( n = 214) and dapagliflozin 10 mg ( n = 213) in patients with T2DM. Serum adipokines (adiponectin and leptin) were measured at baseline and week 24. Analyses were adjusted for baseline values and weight change to determine whether between-treatment differences in adipokine changes persisted after accounting for body weight change, and associations between adipokine changes and key metabolic parameters were assessed. Results After 24 weeks, both SGLT2 inhibitors significantly reduced HbA1c with no between-group difference (− 0.92% vs. −0.87%). Adiponectin increased in both groups (1.61 vs. 1.26 mg/L) without a significant difference (rank-based ANCOVA P = 0.3520). Leptin decreased in both groups, with a greater reduction observed with enavogliflozin than with dapagliflozin (− 2.08 vs. −1.09 µg/L, rank-based ANCOVA P = 0.0113), and this difference persisted after adjustment for weight change and other covariates. In the minimal weight loss group (< 3%), leptin decreased with enavogliflozin (− 0.90 µg/L) but increased with dapagliflozin (1.71 µg/L; P = 0.020), whereas no between-group difference was seen in the effective weight loss group (≥ 3%). Changes in leptin correlated positively with changes in insulin, C-peptide, and HOMA-IR. Conclusion Enavogliflozin showed a greater reduction in leptin than dapagliflozin, which persisted after adjustment for weight change.