Differential effects of imeglimin and metformin on insulin and incretin secretion-An exploratory randomized controlled trial

Diabetes Obes Metab. 2025 Feb;27(2):856-865. doi: 10.1111/dom.16086. Epub 2024 Nov 26.

Abstract

Aims: Imeglimin is a new oral anti-diabetic drug with a similar structure to that of metformin; however, unlike metformin, clinical trials indicate that imeglimin elicits its glucose-lowering effect mainly by enhancement of insulin secretion. The comparative effects of the two drugs on incretin secretion remains to be elucidated.

Materials and methods: A single-center, open-label, randomized controlled trial was conducted in patients with type 2 diabetes who were drug-naïve or were on a single oral hypoglycaemic agent (OHA). For patients taking a single OHA, an 8-week washout period was employed before randomization. Participants were randomized to the imeglimin group (IME, 2000 mg/day) or the metformin group (MET, 1000 mg/day), and OGTT was performed before treatment and after 12 and 24 weeks of treatment.

Results: The reduction in HbA1c at 24 weeks was similar in IME and MET. OGTT revealed a comparable decrease in post-challenge blood glucose excursion in both groups, but insulin levels were increased only in IME. Total and active glucagon-like peptide-1 (GLP-1) levels were increased in both IME and MET; however, total and active glucose-dependent insulinotropic peptide (GIP) levels were increased only in IME. Interestingly, while an increase in insulin levels in IME was positively correlated with an increase in GLP-1 at 12 weeks, it was correlated only with an increase in GIP at 24 weeks.

Conclusions: Unlike metformin, imeglimin enhances GIP secretion as well as GLP-1 secretion, in addition to its direct insulinotropic mechanism of glucose control, emphasizing its potential as a therapeutic option in the treatment of patients with diabetes.

Keywords: imeglimin; incretin; metformin; randomized controlled trial.

Publication types

  • Randomized Controlled Trial
  • Comparative Study

MeSH terms

  • Aged
  • Blood Glucose* / drug effects
  • Blood Glucose* / metabolism
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / metabolism
  • Female
  • Glucagon-Like Peptide 1 / metabolism
  • Glucose Tolerance Test
  • Glycated Hemoglobin* / analysis
  • Glycated Hemoglobin* / drug effects
  • Glycated Hemoglobin* / metabolism
  • Humans
  • Hypoglycemic Agents* / pharmacology
  • Hypoglycemic Agents* / therapeutic use
  • Incretins* / therapeutic use
  • Insulin Secretion / drug effects
  • Insulin* / blood
  • Insulin* / metabolism
  • Male
  • Metformin* / pharmacology
  • Metformin* / therapeutic use
  • Middle Aged
  • Triazines

Substances

  • Metformin
  • Incretins
  • Hypoglycemic Agents
  • Insulin
  • imeglimin
  • Blood Glucose
  • Glycated Hemoglobin
  • Glucagon-Like Peptide 1
  • hemoglobin A1c protein, human
  • Triazines

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