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

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.