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.