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.

Abstract

AimsTo 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.MethodsThe 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.ResultsA 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.ConclusionsThis 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.