Efficacy and safety of fasiglifam (TAK-875), a G protein-coupled receptor 40 agonist, in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise: a randomized, double-blind, placebo-controlled, phase III trial

Aim: To assess the efficacy and safety of fasiglifam 25 and 50 mg in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise. Methods: This phase III, double-blind, placebo-controlled, multicentre study included 192 patients randomized to once-daily treatment with fasiglifam 25 mg (n=63) or 50 mg (n=62) or placebo (n=67) for 24 weeks. The primary efficacy endpoint was the change from baseline in glycated haemoglobin (HbA1c) at week 24. Results: At week 24, both fasiglifam groups had significantly reduced HbA1c levels compared with the placebo group (p<0.0001). The least squares mean change from baseline in HbA1c was 0.16% with placebo, -0.57% with fasiglifam 25 mg and -0.83% with fasiglifam 50 mg. The percentage of patients who achieved an HbA1c target of <6.9% at week 24 was also significantly higher (p<0.05) for fasiglifam 25 mg (30.2%) and 50 mg (54.8%) compared with placebo (13.8%). Fasiglifam significantly reduced fasting plasma glucose levels at all assessment points, starting from week 2. The incidence and types of treatment-emergent adverse events in each fasiglifam group were similar to those in the placebo group, and hypoglycaemia was reported in 1 patient receiving fasiglifam 50 mg. There were no clinically meaningful changes in body weight in any treatment group. Conclusions: Fasiglifam significantly improved glycaemic control and was well tolerated, with a low risk of hypoglycaemia in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise; however, in a recent review of data from overall fasiglifam global clinical trials, concerns about liver safety arose and the clinical development of fasiglifam was terminated after this trial was completed.