Efficacy and safety of teneligliptin added to glimepiride in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled study with an open-label, long-term extension

Diabetes Obes Metab. 2014 May;16(5):418-25. doi: 10.1111/dom.12235. Epub 2013 Dec 10.

Abstract

Aims: To assess the efficacy and safety of teneligliptin in combination with glimepiride in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with glimepiride monotherapy.

Methods: In the initial 12-week, double-blind, placebo-controlled, parallel-group period, 194 patients [haemoglobin A1c (HbA1c): 8.4 ± 0.8%; fasting plasma glucose (FPG): 164.2 ± 28.1 mg/dl] were randomized to either teneligliptin 20 mg or placebo once daily while continuing stable glimepiride therapy. This randomized period was then followed by a 40-week, open-label period, where all patients received teneligliptin once daily. The primary endpoint was the change in HbA1c from baseline to week 12.

Results: Teneligliptin reduced HbA1c significantly compared with placebo at week 12. The placebo-subtracted change in HbA1c was -1.0 ± 0.1% [least-squares (LS) mean ± s.e., p < 0.001]. Teneligliptin also significantly reduced FPG and 2-h postprandial glucose (PPG) as compared with placebo at week 12; the placebo-subtracted changes were -27.1 ± 3.2 and -49.1 ± 6.2 mg/dl (LS mean ± s.e., both p < 0.001), respectively. The blood glucose-lowering effects were sustained throughout the 40-week open-label period. The incidence rates of adverse events and adverse drug reactions, including hypoglycaemia, during the double-blind randomized period were similar in both groups. Therefore, teneligliptin was generally well tolerated when used in combination with glimepiride.

Conclusions: The addition of teneligliptin was effective and generally well tolerated in Japanese patients with T2DM inadequately controlled with glimepiride monotherapy. The improvements in glycaemic control were maintained for up to 52 weeks.

Trial registration: ClinicalTrials.gov NCT00971243 NCT01026194.

Keywords: DPP-4 inhibitor; HbA1c; Japanese; glimepiride; teneligliptin; type 2 diabetes mellitus.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asian People
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Fasting
  • Glycated Hemoglobin / drug effects
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemia / blood
  • Hypoglycemia / chemically induced*
  • Hypoglycemia / epidemiology
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Postprandial Period
  • Pyrazoles / administration & dosage
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Sulfonylurea Compounds / therapeutic use*
  • Thiazolidines / administration & dosage
  • Thiazolidines / adverse effects
  • Thiazolidines / therapeutic use*
  • Treatment Outcome

Substances

  • 3-(4-(4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl)pyrrolidin-2-ylcarbonyl)thiazolidine
  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Pyrazoles
  • Sulfonylurea Compounds
  • Thiazolidines
  • hemoglobin A1c protein, human
  • glimepiride

Associated data

  • ClinicalTrials.gov/NCT00971243
  • ClinicalTrials.gov/NCT01026194