Efficacy and safety of tofogliflozin in Japanese patients with type 2 diabetes mellitus with inadequate glycaemic control on insulin therapy (J‐STEP/INS): Results of a 16‐week randomized, double‐blind, placebo‐controlled multicentre trial

AIMS: To assess the effects of 16 weeks of tofogliflozin (sodium‐glucose co‐transporter‐2 [SGLT2] inhibitor) treatment vs placebo on glycated haemoglobin (HbA1c) levels in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with insulin monotherapy or insulin plus a dipeptidyl peptidase‐4 (DPP‐4) inhibitor. METHODS: The study comprised a 16‐week, multicentre, double‐blind, placebo‐controlled period and a 36‐week extension (NCT02201004). Men and women (aged ≥20 and ≤75 years) with T2DM (HbA1c ≥7.5% and ≤10.5%) were randomized 2:1 to tofogliflozin 20 mg once/day or placebo. The primary endpoint was change in HbA1c from baseline. Insulin reduction was not permitted during this study. RESULTS: A total of 211 patients were randomized (141 tofogliflozin, 70 placebo). Addition of tofogliflozin to insulin therapy was significantly superior to placebo for lowering HbA1c (−0.59 vs +0.48%; P < .0001), fasting plasma glucose (−27.2 vs +5.3 mg/dL; P < .0001), postprandial plasma glucose (−65.0 vs +3.2 mg/dL; P < 0.0001), serum uric acid (−0.18 vs +0.07 mg/dL; P = .0062), body weight (−1.34 vs +0.03 kg; P < .0001) and daily insulin dose (−1.3 vs −0.2 U, P = .0152). Hypoglycaemia occurred in 30.7% of patients receiving tofogliflozin vs 21.4% for placebo. Two patients treated with tofogliflozin each had a genital or urinary tract infection. CONCLUSIONS: This 16‐week double‐blind study indicated that, in patients with T2DM whose HbA1c levels were poorly controlled with insulin monotherapy or insulin plus a DPP‐4 inhibitor, addition of tofogliflozin was an effective treatment option with an acceptable safety profile.