Lobeglitazone improves glycaemic control as add-on therapy to empagliflozin plus metformin in patients with type 2 diabetes mellitus: A double-blind, randomised, placebo-controlled trial

Abstract

Aims This study aimed to evaluate the efficacy and safety of triple therapy with lobeglitazone 0.5 mg as an add-on treatment compared with placebo in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and empagliflozin. Materials and Methods In this Phase 3, multicentre, double-blind, randomised trial, patients with T2DM who had an insufficient response to metformin (>= 1000 mg/day) and empagliflozin 10 mg/day (Study 1) or 25 mg/day (Study 2) were randomised to receive either lobeglitazone 0.5 mg/day, or placebo once daily for 24 weeks. Participants then entered an open-label extension phase for an additional 28 weeks, bringing the total treatment duration to 52 weeks. The primary endpoint was the change from baseline in glycated haemoglobin (HbA1c) at 24 weeks. Results At 24 weeks, the mean change in HbA1c was significantly greater with lobeglitazone than with placebo, regardless of the background empagliflozin dose (-0.71%; 95% confidence interval, -0.88 to -0.55; p < 0.001 in Study 1 and -0.62%; -0.79 to -0.45; p < 0.001 in Study 2). A higher proportion of patients achieved HbA1c levels <7% with lobeglitazone compared to placebo (48.7% vs. 13.4% in Study 1, and 44.4% vs. 13.0% in Study 2; p < 0.001). Although the incidence of adverse events was numerically different between groups, no statistically significant differences were observed, indicating a generally comparable profile for the triple combination therapy with metformin, empagliflozin, and lobeglitazone. Conclusions Lobeglitazone as an add-on to empagliflozin and metformin significantly improved glycaemic control in patients with T2DM inadequately controlled on metformin and empagliflozin dual therapy. The treatment was well tolerated, with a low incidence of adverse events.