Efficacy and safety of dapagliflozin as a monotherapy for type 2 diabetes mellitus in Japanese patients with inadequate glycaemic control: a phase II multicentre, randomized, double‐blind, placebo‐controlled trial

AIM: Dapagliflozin is a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor under development as a treatment for type 2 diabetes mellitus (T2DM). This study assessed the efficacy and safety of dapagliflozin monotherapy in Japanese T2DM patients with inadequate glycaemic control. METHODS: Patients (n = 279) were randomized to receive dapagliflozin (1, 2.5, 5 or 10 mg/day) or placebo once daily for 12 weeks. The primary endpoint was change from baseline in haemoglobin A1c (HbA1c) at week 12. Secondary endpoints included change from baseline in fasting plasma glucose (FPG) and proportion of patients achieving HbA1c <7.0% at week 12. RESULTS: Significant reductions in HbA1c were seen with all dapagliflozin doses (-0.11 to -0.44%) versus placebo (+0.37%). Reductions were also observed in FPG with dapagliflozin (-0.87 to -1.77 mmol/l -15.61 to -31.94 mg/dl) versus placebo (+0.62 mmol/l +11.17 mg/dl). No significant difference in the proportion of patients achieving HbA1c levels <7.0% was noted with dapagliflozin versus placebo. Adverse events (AEs) were more frequent with dapagliflozin (40.7-53.8%) versus placebo (38.9%) and were mostly mild/moderate in intensity. Three hypoglycaemic events were reported (1 each with placebo, dapagliflozin 2.5 mg and 10 mg). The frequency of signs and symptoms suggestive of urinary tract or genital infections was 0-3.8 and 0-1.8% respectively with dapagliflozin and 1.9 and 0% with placebo. No AEs of pyelonephritis were observed. CONCLUSIONS: Compared with placebo, dapagliflozin significantly reduced hyperglycaemia over 12 weeks with a low risk of hypoglycaemia in Japanese T2DM patients with inadequate glycaemic control.