Efficacy and safety of empagliflozin twice daily versus once daily in patients with type 2 diabetes inadequately controlled on metformin: a 16-week, randomized, placebo-controlled trial

Patients with type 2 diabetes mellitus (T2DM) with a glycated haemoglobin (HbA1c) level ≥7 and ≤10% were randomized to receive empagliflozin12.5 mg twice daily (n = 219), 25 mg once daily (n = 218), 5 mg twice daily (n = 219) or 10 mg once daily (n = 220), or placebo (n = 107) as add-on to stable-dose metformin immediate release (IR) twice daily for 16 weeks. The primary endpoint was change from baseline in HbA1c at week 16. At week 16, change from baseline in HbA1c with empagliflozintwice daily was non-inferior to empagliflozinonce daily and vice versa. The adjusted mean (95% confidence interval) difference in change from baseline in HbA1c with empagliflozin12.5 mg twice daily versus 25 mg once daily was −0.11% (−0.26, 0.03), and with empagliflozin5 mg twice daily versus 10 mg once daily it was −0.02% (−0.16, 0.13). All empagliflozinregimens were well tolerated; thus, when used as add-on to metformin IR in patients with T2DM, the therapeutic effect of empagliflozintwice-daily and once-daily regimens can be considered equivalent.