A 52‐Week Efficacy and Safety Study of Teneligliptin, as an Add‐On to Empagliflozin and Metformin in Patients With Type 2 Diabetes Mellitus: A Randomised, Double‐Blind, Placebo‐Controlled Phase 3 Trial ( TERA305 Study)

ABSTRACT Aims To evaluate the long‐term efficacy and safety of teneligliptin add‐on in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and empagliflozin. Materials and Methods In this randomised, double‐blind, phase 3 trial, 214 patients received teneligliptin 20 mg ( n = 107) or placebo ( n = 107) once daily for 24 weeks, in addition to metformin (≥ 1000 mg/day) and empagliflozin (25 mg/day). In a subsequent 28‐week open‐label extension, all patients received teneligliptin 20 mg/day. The primary endpoint was HbA1c change from baseline to week 24. Results At week 24, the least squares mean (LSM) change in HbA1c from baseline was −0.70% ± 0.06% in the teneligliptin group and −0.03% ± 0.06% in the placebo group, with a placebo‐adjusted LSM change of −0.67% (95% CI, −0.84 to −0.49; p < 0.0001), demonstrating the superiority of teneligliptin. A significant between‐group difference was already evident at week 4 (placebo‐adjusted LSM change, −0.36%; p < 0.0001). Significant reductions in fasting plasma glucose and glycated albumin and improvement in pancreatic β ‐cell function were observed at week 24. During the open‐label extension, glycaemic improvements were maintained through week 52, although no concurrent randomised control was available beyond week 24. Placebo‐group patients achieved a similar benefit after switching to teneligliptin. Safety outcomes did not differ between groups. Conclusions Adding teneligliptin to metformin and empagliflozin in patients with inadequately controlled T2DM significantly improved glycaemic control and β ‐cell function over 24 weeks and was well tolerated through 52 weeks. Trail Registration ClinicalTrials.gov Identifier: NCT05504226.