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.

A Randomized, Open-Label, Crossover Trial to Assess Bioequivalence of Teneligliptin 10 mg Twice-Daily with Teneligliptin 20 mg Once-Daily

“…In most clinical trials, teneligliptin has been studied as a single dose regimen (teneligliptin 20 mg q.d.) [14,16]. To establish that twice daily regimen of teneligliptin would have similar bioavailability to single daily dose, our study compared the steady state PK/PD of the two regimens in healthy adult subjects.…”

“…Similar results concerning DPP-4 inhibition have also been observed in a 4-week study conducted by Eto, et al, the percentage of DPP-4 inhibition was 81.3% and 89.7%, 2-hour after administration of teneligliptin 10 and 20 mg q.d., respectively [6]. Teneligliptin is generally well-tolerated in subjects with T2DM when used as monotherapy or add-on therapy to other antidiabetic drugs such as metformin, glimepiride, and pioglitazone [9,11,12,14,18]. In a study investigating teneligliptin as a monotherapy, the most commonly reported AEs were nasopharyngitis, a positive urine ketone body, urine glucose, and urinary protein [10].…”

“…In several clinical trials, teneligliptin was administered 10, 20, and 40 mg once daily (q.d.) either as a monotherapy or in combination with other drugs [9,11,[14][15][16][17][18][19]. Currently, the recommended dosage of teneligliptin is 20 mg q.d.…”

Pharmacokinetics of a Fixed-Dose Combination of Teneligliptin Hydrochloride Hydrate and Modified-Release Metformin Under Fasting and Fed Conditions in Healthy Subjects

“…The efficacy and safety of teneligliptin and metformin dual combination therapy was recently confirmed once again in Asian patients in a Chinese clinical trial. 13 This trial compared teneligliptin versus placebo for type 2 diabetes patients who were inadequately controlled with metformin and lifestyle modification. The inclusion criteria were almost the same as those in a previous study conducted in Europe.…”

“…At 24 weeks, both clinical trials showed that the number of patients with glycated hemoglobin less than 7% was over 40%, and the glycated hemoglobin decreased by approximately 0.8%. 13 , 14 Providing a stabilized FDC formulation for a drug whose efficacy has been proven as described above has the advantage of possibly reducing the burdens of administration and improving low medication compliance in patients with type 2 diabetes.…”