Fasiglifam for glycaemic control in people with type 2 diabetes: A phase III, placebo-controlled study

Diabetes Obes Metab. 2017 Dec;19(12):1714-1721. doi: 10.1111/dom.13004. Epub 2017 Jul 11.

Abstract

Aim: To investigate the effect of fasiglifam on glycaemic control in people with type 2 diabetes mellitus (T2DM).

Methods: In total, 421 people with T2DM and glycated haemoglobin (HbA1c) ≥7.0% and ≤10.5% who had received only diet and exercise treatment for ≥12 weeks prior to screening were randomized to receive fasiglifam 25 or 50 mg or placebo. The primary efficacy endpoint was change from baseline in HbA1c at week 24.

Results: The mean participant age was 53.5 years, mean baseline body mass index 32.3 kg/m2 , and mean baseline HbA1c level 8.05%. Least squares mean changes in HbA1c from baseline to week 24 were: -0.93% (fasiglifam 50 mg), -0.65% (fasiglifam 25 mg) and -0.17% (placebo). Treatment-emergent adverse events (TEAEs) occurred in 53.3%, 48.2% and 39.9% of participants receiving fasiglifam 25 mg, fasiglifam 50 mg, and placebo, respectively. Three participants in each group experienced a serious adverse event (AE). Nine participants had alanine aminotransferase (ALT) elevations >3× upper limit of normal: 5 (3.6%) in the fasiglifam 25-mg group, 4 (2.8%) in the fasiglifam 50-mg group, and none in the placebo group.

Conclusions: The data indicate that fasiglifam effectively reduced HbA1c from baseline for 24 weeks in participants with T2DM. The incidence of TEAEs was higher in the fasiglifam groups; however, the incidence of serious AEs was low overall and similar between groups. ALT elevations were observed only in the fasiglifam groups, which contributed to the decision to terminate the fasiglifam programme after completion of the present study.

Keywords: antidiabetic drug; glycaemic control; phase III study; type 2 diabetes.

Publication types

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

MeSH terms

  • Benzofurans / administration & dosage
  • Benzofurans / adverse effects*
  • Benzofurans / therapeutic use
  • Body Mass Index
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / physiopathology
  • Combined Modality Therapy / adverse effects
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diet, Diabetic
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Exercise
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hyperglycemia / prevention & control*
  • Hypoglycemia / chemically induced
  • Hypoglycemia / prevention & control*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use
  • Liver / drug effects
  • Liver / physiopathology
  • Lost to Follow-Up
  • Male
  • Middle Aged
  • Obesity / complications
  • Patient Dropouts
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / metabolism
  • Sulfones / administration & dosage
  • Sulfones / adverse effects*
  • Sulfones / therapeutic use

Substances

  • Benzofurans
  • FFAR1 protein, human
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Receptors, G-Protein-Coupled
  • Sulfones
  • TAK-875
  • hemoglobin A1c protein, human