Triple therapy with low‐dose dapagliflozin plus saxagliptin versus dual therapy with each monocomponent, all added to metformin, in uncontrolled type 2 diabetes

摘要

Abstract Aim To evaluate the efficacy and safety of triple therapy with low‐dose dapagliflozin plus saxagliptin added to metformin in uncontrolled type 2 diabetes. Materials and methods This 24‐week, double‐blind trial (NCT02681094) randomized 883 patients (glycated haemoglobin [HbA1c] 7.5‐10.0%) on metformin ≥1500?mg/d to add‐on dapagliflozin 5 mg/d plus saxagliptin 5 mg/d or to add‐on of either monocomponent. The primary endpoint was change in HbA1c from baseline. Results Baseline mean?±?SD patient characteristics were: age 56.7?±?10.5 years; HbA1c 8.2?±?0.9%; and diabetes duration 7.6?±?6.1 years. Triple therapy significantly decreased HbA1c versus dual therapy (?1.03% vs. ?0.63% [dapagliflozin] vs. ?0.69% [saxagliptin]; P ??.0001). More patients achieved HbA1c 7.0% with triple versus dual therapy (41.6% vs. 21.8% [dapagliflozin; P ??.0001] vs. 29.8% [saxagliptin; P = .0018]). Triple therapy significantly decreased fasting plasma glucose (?1.5?mmol/L vs. ?1.1 mmol/L [dapagliflozin; P = .0135] vs. ?0.7 mmol/L [saxagliptin; P ??.0001]) and body weight (?2.0 kg vs. ?0.4 kg [saxagliptin; P ??.0001]), and β‐hydroxybutyrate levels were lower than with dapagliflozin plus metformin (mean difference??0.51; P = .0009). Urinary tract/genital infections and hypoglycaemia occurred in 5.0% and 5.8% of patients, respectively, with triple therapy. Conclusions Triple therapy with once‐daily dapagliflozin 5 mg, saxagliptin 5 mg and metformin significantly improved glycaemic control versus dual therapy with either agent added to metformin in uncontrolled type 2 diabetes, and was generally well tolerated.