title: Imeglimin increases glucose-dependent insulin secretion and improves β-cell function in patients with type 2 diabetes.
abstract: OBJECTIVE
  To assess the glucose-stimulated insulin secretion effect of imeglimin in patients with type 2 diabetes.
  
  
  METHODS
  We conducted a double-blind, randomized, placebo-controlled study in 33 patients with type 2 diabetes [glycated haemoglobin 6.8 ± 0.1% (51 mmol/mol)], who were drug-naïve or withdrawn from their previous metformin monotherapy for 2 weeks and received imeglimin 1500 mg twice daily or placebo for 1 week. Glucose-stimulated insulin secretion was assessed using a hyperglycaemic clamp. The primary endpoint was insulin secretion as defined by total insulin response [incremental area under the curve (iAUC)0-45 min ] and insulin secretion rate (ISR) calculated from C-peptide deconvolution. β-cell glucose sensitivity at steady state (second phase: 25-45 min), hepatic insulin extraction and insulin clearance were also calculated.
  
  
  RESULTS
  Imeglimin treatment for 7 days raised the insulin secretory response to glucose by +112% (iAUC0-45 , p = 0.035), first-phase ISR by +110% (p = 0.034) and second-phase ISR by +29% (p = 0.031). Imeglimin improved β-cell glucose sensitivity by +36% (p = 0.034) and tended to decrease hepatic insulin extraction (-13%; p = 0.056). Imeglimin did not affect glucagon secretion.
  
  
  CONCLUSIONS
  In patients with type 2 diabetes, imeglimin improves β-cell function, which may contribute to the glucose-lowering effect observed with imeglimin in clinical trials.
authors.affiliation: Metabolic (Modeling) Unit, Institute of Biomedical Engineering, Padova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Pacini
authors.affiliation: Metabolic (Modeling) Unit, Institute of Biomedical Engineering, Padova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Mari
authors.affiliation: Poxel SA, Lyon, France.
authors.forename: P
authors.initials: P
authors.lastname: Fouqueray
authors.affiliation: Poxel SA, Lyon, France.
authors.forename: S
authors.initials: S
authors.lastname: Bolze
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Düsseldorf, Germany.|Department of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Roden
mesh_terms: D001786:Blood Glucose / Q000187:drug effects*; D002096:C-Peptide / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005934:Glucagon / Q000187:drug effects / Q000378:metabolism; D015309:Glucose Clamp Technique; D065669:Hepatobiliary Elimination; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D014227:Triazines / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D014227:Triazines; D005934:Glucagon; C575881:imeglimin
keywords: Glucose-lowering drug; beta cell; clinical trial; insulin secretion; randomised trial; type 2 diabetes