Empagliflozin as adjunct to insulin in Japanese participants with type 1 diabetes: Results of a 4‐week, double‐blind, randomized, placebo‐controlled phase 2 trial

AIMS: This phase 2, double‐blind, randomized, placebo‐controlled trial (http://clinicaltrials.gov NCT02702011) with 4 sites in Japan investigated the pharmacodynamics (PD), pharmacokinetics (PK) and safety profile of empagliflozin in Japanese participants with type 1 diabetes mellitus (T1DM) as adjunctive therapy to insulin. MATERIALS AND METHODS: Participants using multiple daily injections of insulin for ≥12 months, with HbA1c of 7.5%‐10.0%, entered a 2‐week, open‐label, placebo run‐in period, followed by a 4‐week, double‐blind period during which participants were randomized 1:1:1:1 to receive empagliflozin 2.5 mg (n = 13), empagliflozin 10 mg (n = 12), empagliflozin 25 mg (n = 12) or placebo (n = 11). The primary objective was to assess the effect of empagliflozin vs placebo on urinary glucose excretion (UGE) after 7 days of treatment. RESULTS: PD: Empagliflozin resulted in a dose‐dependent significant increase in 24‐hour UGE compared with placebo (UGE placebo‐corrected mean [95% confidence interval] change from baseline: 2.5 mg, 65.10 [43.29, 86.90] g/24 h; 10 mg, 81.19 [58.80, 103.58] g/24 h; 25 mg, 98.11 [75.91, 120.31] g/24 h). After 4 weeks of treatment, UGE increase was associated with improved glycaemic control, reduced body weight and decreased insulin needs. Empagliflozin treatment also resulted in dose‐dependent increases in serum ketone bodies and free fatty acids. PK: Plasma empagliflozin levels increased in a dose‐dependent manner and peaked at 1.5 hours. In this short study, empagliflozin was well tolerated, with no increase in rate of hypoglycaemia and no diabetic ketoacidosis events reported. CONCLUSIONS: Based on this short‐duration phase 2 study, the PK/PD profile of empagliflozin in Japanese participants with T1DM is comparable to that of non‐Japanese participants.