Abstract
BACKGRUOUND: Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin. METHODS: In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500). RESULTS: Adjusted mean change of HbA1c at week 24 was -0.80% with enavogliflozin and -0.75% with dapagliflozin (difference, -0.04%; 95% confidence interval, -0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was -32.53 and -29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (-1.85 vs. -1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (-3.77 kg vs. -3.58 kg) and blood pressure (systolic/diastolic, -5.93/-5.41 mm Hg vs. -6.57/-4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated. CONCLUSION: Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone.