Efficacy and Safety of Fixed-Dose Combinations of Sitagliptin and Empagliflozin as Add-On to Metformin in Korean Patients With Type 2 Diabetes: A Randomised, Double-Blind, Multi-Centre, Placebo-Controlled, Phase III Trial

Background: Type 2 diabetes mellitus (T2DM) is a progressive, multi-organ disorder that often requires intensive combination therapy. This Phase III, randomised, double-blind, placebo-controlled study evaluated the efficacy and safety of two fixed-dose combinations (FDCs) of sitagliptin 100 mg with empagliflozin 10 mg (DW1026C1) or empagliflozin 25 mg (DW1026C2) as add-on therapy for patients with inadequately controlled T2DM. Methods: Two hundred thirty adults with T2DM inadequately controlled by metformin (≥ 1000 mg/day) and sitagliptin (100 mg) were 1:1:1 randomised to receive DW1026C1 (E10 group, n = 77), DW1026C2 (E25 group, n = 76), or a placebo (n = 77). Treatment was administered for 24 weeks, followed by a 28-week extension period. The primary endpoint was the change in HbA1c from baseline to Week 24. Results: Baseline characteristics were similar among groups. At Week 24, both active treatments demonstrated statistically significant HbA1c reductions versus the placebo. The least square mean differences [95% CI] versus the placebo were −0.54% [−0.78, −0.29] for E10 group and −0.61% [−0.85, −0.36] for E25 group (both p < 0.0001). Fasting plasma glucose (FPG), insulin resistance, body weight, systolic blood pressure, albumin-creatinine ratio and high-density lipoprotein cholesterol also improved in the active groups. Reductions in HbA1c, FPG and insulin resistance were sustained in Week 52. Safety profiles were favourable with adverse events similar in frequency and no increased hypoglycaemia risk. Conclusion: Sitagliptin/empagliflozin FDC doses achieved improvements in glycaemic control at 24 weeks, which was maintained through 52 weeks. These benefits were accompanied by a favourable safety profile, including a very low risk of hypoglycaemia. Trial Registration: NCT07076056.