Long-term safety and efficacy of tofogliflozin as add-on to insulin in patients with type 2 diabetes: Results from a 52-week, multicentre, randomized, double-blind, open-label extension, Phase 4 study in Japan (J-STEP/ INS)

Aims: To evaluate the long-term safety and efficacy of tofogliflozin as an add-on treatment to insulin over 52 weeks. Materials and methods: This 52-week, multicentre, Phase 4 study consisted of a 16-week, randomized, double-blind, placebo-controlled phase and a 36-week open label extension phase (NCT02201004). Japanese patients with type 2 diabetes mellitus, aged 20 to 75 years, with suboptimal glycaemic control (7.5%-10.5%) receiving insulin monotherapy (basal-bolus, bolus, premix [low and high] and basal) or receiving combination therapy with basal insulin and dipeptidyl peptidase-4 inhibitor were eligible for participation. Patients who received tofogliflozin throughout the study (52 weeks) were referred to as the 'tofo-tofo group' and patients who received placebo and tofogliflozin (36 weeks) were referred to as the 'pla-tofo group'. Results: A total of 210 patients received treatment per randomization. Hypoglycaemia was the most common treatment-emergent adverse event (AE) (42.9% in the tofo-tofo group and 29.4% in the pla-tofo group). Patients reported genital infection, urinary tract infection, excessive urination and AEs related to volume depletion (2.1%, 2.1%, 7.1% and 10.0% of patients in the tofotofo group, and 0%, 1.5%, 2.9% and 7.4% of patients in the pla-tofo group, respectively). Mean HbA1c and body weight at baseline (mean changes +/- standard error from baseline to Week 52) in the tofo-tofo and pla-tofo groups were 8.53% (-0.76% +/- 0.077) and 8.40% (-0.73% +/- 0.102); 68.84 kg (-1.52 kg +/- 0.207) and 72.24 kg (-2.13 kg +/- 0.313), respectively. Conclusions: This study demonstrates the safety and efficacy of tofogliflozin as add-on to insulin therapy in type 2 diabetes mellitus patients, offering a new therapeutic solution to diabetes management.