Efficacy and Safety of Dapagliflozin Add-on Therapy to Evogliptin plus Metformin Combinations in Inadequately Controlled Patients with Type 2 Diabetes-A 24-Week, Randomized, Double-blind, Placebo-Controlled, Parallel-Design, Phase 3 Trial

Background and Aims: We aimed to evaluate the efficacy and safety of dapagliflozin versus placebo as add-on therapy in patients with type 2 diabetes and inadequate glycemic control with evogliptin and metformin combinations. Materials and Methods: In this multi-center, double-blind, randomized, placebo-controlled phase 3 trial, patients with HbA1c ≥7.0% and ≤10.5% who had received stable-dose (≥1000 mg) metformin and evogliptin 5mg for at least 8 weeks were randomized to receive dapagliflozin 10mg or placebo once daily for 24 weeks. All patients continued treatment with metformin and evogliptin 5 mg. The primary endpoint was the change from baseline in HbA1c after 24 weeks of double-blind treatment. Results:198 patients were randomized and 195 patients were included in efficacy analyses (dapagliflozin: 96, placebo: 99). At week 24, dapagliflozin significantly reduced HbA1c. The least square [LS] mean difference in the change from baseline with dapagliflozin versus placebo was -0.70% (95% confidence interval [–0.91, –0.48], p<0.0001). The proportion of patients achieving HbA1c <7% was higher in dapagliflozin group (42.71% versus 16.16% in placebo; p=0.0002). Compared to placebo, dapagliflozin treatment significantly reduced fasting plasma glucose, mean daily glucose, fasting insulin and HOMA-IR at week 24. Adiponectin was significantly increased from baseline over 24 weeks with dapagliflozin. Adverse event rates were similar between groups (dapagliflozin: 27.55%, placebo:27.27%) including hypoglycemia and genital infection. Conclusions: Triple combination with dapagliflozin add-on to evogliptin plus metformin improved glycemic control and is well tolerated in patients with type 2 diabetes who are not adequately controlled with evogliptin and metformin combination. Disclosure I.Jeong: None. K.Choi: None. K.Han: None. K.Kim: None. I.Kim: None. S.Han: None. W.Lee: None. S.Yoo: None.