Henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial

Aim To evaluate the efficacy and safety of henagliflozin in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin. Material and Methods This multicentre phase 3 trial included a 24-week randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. Patients with a glycated haemoglobin (HbA1c) level of 7.0% (53 mmol/mol) to 10.5% (91 mmol/mol) were randomized and treated with once-daily placebo (n = 161), henagliflozin 5 mg (n = 162), or henagliflozin 10 mg (n = 160). After 24 weeks, patients on placebo were switched to 5 mg or 10 mg henagliflozin for the additional 28-week treatment, and patients on henagliflozin during 24-week treatment period maintained this initial therapy. The primary endpoint was change in HbA1c from baseline to Week 24. Results At Week 24, the least squares mean HbA1c changes versus placebo from baseline were - 0.76% (-8.3 mmol/mol) and - 0.80% (-8.7 mmol/mol) for henagliflozin 5 and 10 mg, respectively (all P < 0.0001). Compared with the placebo group, both doses of henagliflozin lowered fasting plasma glucose, 2-hour postprandial plasma glucose, body weight and blood pressure, and increased the proportions of patients achieving HbA1c <7.0% (53 mmol/mol) at Week 24. The trends in these improvements were sustained over an additional 28 weeks. Slightly higher proportions of ketosis and presence of urine ketone bodies were observed in patients treated with henagliflozin compared to placebo at Week 24. No diabetic ketoacidosis or episodes of severe hypoglycaemia were reported. Conclusions Henagliflozin 5 mg or 10 mg as add-on therapy to metformin provided a new therapeutic option for the treatment of T2DM patients who have inadequate glycaemic control with metformin alone, and was generally well tolerated.