Efficacy and safety of teneligliptin added to metformin in Chinese patients with type 2 diabetes mellitus inadequately controlled with metformin: A phase 3, randomized, double-blind, placebo-controlled study

Abstract

Introduction: We evaluated the efficacy and safety of teneligliptin compared with placebo when added to metformin therapy in Chinese patients with type 2 diabetes inadequately controlled with metformin monotherapy.

Methods: This multicentre, randomized, double-blind, placebo-controlled, parallel-group study enrolled type 2 diabetes patients with glycosylated haemoglobin (HbA1c) 7.0%-<10.0% and fasting plasma glucose (FPG) <270 mg/dl, receiving a stable metformin dose ≥1000 mg/day. Teneligliptin 20 mg or placebo was administered orally once daily (qd) before breakfast for 24 weeks. The primary efficacy end-point was change in HbA1c from baseline to Week 24. Safety end-points included the incidence of adverse events (AEs).

Results: The least square mean (LSM) change from baseline (standard error [SE]) was -0.72 (0.07) (95% confidence intervals [CI], -0.87, -0.58) for teneligliptin and -0.01 (0.07) (95% CI, -0.16, 0.13) for placebo. The differences (LSM ± SE) between the placebo and teneligliptin groups in HbA1c and FPG were -0.71% ± 0.11% (p < .0001) and -16.5 ± 4.7 mg/dl (p = .0005), respectively. Teneligliptin yielded significant changes in HbA1c (-0.81%; p < .0001) and FPG (-22.2 mg/dl; p < .0001) at Week 12. At Week 24, more patients achieved HbA1c <7.0% with teneligliptin (41.7%) compared with placebo (16.1%; p < .0001). Treatment-emergent AE incidence was similar with teneligliptin (58.9%) and placebo (68.3%); upper respiratory tract infection, hyperuricaemia and hyperlipidaemia were the most common AEs.

Conclusions: Teneligliptin 20 mg qd for 24 weeks added to ongoing metformin treatment significantly decreased HbA1c and FPG levels compared with placebo in Chinese type 2 diabetes patients. The combination was safe and tolerable.

Trial registration: ClinicalTrials.gov NCT02888691.

Keywords: diabetes mellitus; dipeptidyl peptidase‐IV inhibitors; metformin; type 2.

Conflict of interest statement

Linong Ji has received personal fees from Mitsubishi Tanabe Pharma Development (Beijing) Co., Ltd. Yi Wang is an employee of Mitsubishi Tanabe Pharma Development (Beijing) Co., Ltd. Gen Takayanagi is an employee of Mitsubishi Tanabe Pharma Development America, Inc. The remaining authors have no conflicts of interest to declare.

© 2021 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.

Figures

FIGURE 1

Patient disposition

FIGURE 2

Mean change in HbA1c from baseline to Week 24 and Week 24 (LOCF) in the FAS. Baseline is defined as the most recent assessment prior to randomization. Missing HbA1c values at Week 24 were imputed using the LOCF method. CI, confidence interval; FAS, full analysis set; HbA1c, glycosylated haemoglobin; LOCF, last observation carried forward

FIGURE 3

Mean change in fasting plasma glucose (FPG) from baseline to Week 24 and Week 24 (LOCF) in the FAS. Baseline is defined as the most recent assessment prior to randomization. Missing fasting plasma glucose values at Week 24 were imputed using the LOCF method. CI, confidence interval; FAS, full analysis set; FPG, fasting plasma glucose; LOCF, last observation carried forward