Long‐term effects of dapagliflozin plus saxagliptin versus glimepiride on a background of metformin in patients with type 2 diabetes: Results of a 104‐week extension to a 52‐week randomized, phase 3 study and liver fat MRI substudy

AIM: To report the results of a 104‐week extension to a 52‐week study in which dapagliflozin plus saxagliptin (DAPA+SAXA) improved glycaemic control, liver fat and metabolic variables compared with glimepiride (GLIM) in participants with type 2 diabetes (T2D) receiving background metformin. MATERIALS AND METHODS: This extension to a 52‐week global, multicentre, parallel‐group, active‐controlled, double‐blind study (NCT02419612) continued randomized participants (1:1) on DAPA+SAXA (10/5 mg) plus placebo, or GLIM (1‐6 mg) plus placebo, once daily. Eligible participants were aged ≥18 years, had T2D (glycated haemoglobin [HbA1c] 58.5‐91.3 mmol/mol [7.5%‐10.5%]), and a body mass index of 20.0 to 45.0 kg/m(2), and were receiving metformin (MET; ≥1500 mg/d). Key outcomes were: requirement for treatment intensification, based on HbA1c ≥53 mmol/mol (7%); achieving therapeutic glycaemic response; and changes in adipose tissue and liver fat on magnetic resonance imaging in a substudy. RESULTS: Overall, 382 participants entered and 338 completed the 104‐week extension period (MRI substudy, n = 82). The need for treatment intensification during the 156‐week period was lower for DAPA+SAXA+MET (37.0%) than GLIM+MET (55.6%; hazard ratio 0.52, 95% confidence interval [CI] 0.39‐0.68; P < 0.001). At week 156, 21.4% of DAPA+SAXA+MET versus 11.7% of GLIM+MET participants achieved therapeutic glycaemic response (HbA1c <53 mmol/mol; odds ratio 2.1, 95% CI 1.23‐3.42; P = 0.006). DAPA+SAXA+MET led to greater adjusted mean reductions from baseline in liver fat and visceral and subcutaneous adipose tissue volumes versus GLIM+MET at week 122 (least‐squares mean difference from GLIM+MET −4.89%, −0.41 L and −0.44 L, respectively; nominal P values ≤ 0.008). Safety was consistent with that of the monocomponents. CONCLUSIONS: Overall, glycaemic control, metabolic benefits and efficacy were better maintained with DAPA+SAXA+MET than with GLIM+MET in T2D.