Efficacy and safety of combining empagliflozin in people with type 2 diabetes mellitus uncontrolled with metformin and sitagliptin: A randomised, double-blind, multicentre, therapeutic confirmatory phase 3 clinical trial

Abstract

Aim This study evaluated the efficacy and safety of empagliflozin 10 and 25 mg compared to placebo as add-on treatment for people with type 2 diabetes mellitus (T2DM) uncontrolled after >= 8 weeks of treatment with metformin and sitagliptin. Materials and Methods A randomised, double-blind, multicentre, therapeutic confirmatory, phase 3 clinical trial was conducted in 172 patients with T2DM. Participants with glycosylated haemoglobin (HbA1c) levels 7%-10% receiving sitagliptin and metformin were randomised 1:1:1 to empagliflozin 10 mg, empagliflozin 25 mg, or placebo. The primary endpoint was the change in HbA1c from baseline to week 24. Results After 24 weeks of treatment, HbA1c levels were significantly decreased in the empagliflozin 10 and 25 mg group versus the placebo group; the adjusted mean differences with empagliflozin 10 and 25 mg versus placebo were -0.7% (95% CI -1.0, -0.4; p <.0001) and -0.8% (95% CI -1.1, -0.5; p <.0001), respectively. Fasting plasma glucose levels were also significantly decreased in both empagliflozin groups compared to the placebo group (both p <.0001). More patients reached HbA1c <7% or <6.5% after 24 weeks in the empagliflozin 10 and 25 mg groups versus the placebo group (both p <.05). Efficacy was maintained in the empagliflozin groups during a 28-week extension period. Empagliflozin add-on was associated with improvements in albuminuria and body weight. The incidence of adverse events was similar across groups; add-on empagliflozin was well tolerated. Conclusions These results suggest that coadministration of empagliflozin safely improves glycemic control in Korean patients with T2DM uncontrolled by sitagliptin and metformin.