Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in high-fat-fed rodents

Am J Physiol Endocrinol Metab. 2016 Aug 1;311(2):E461-70. doi: 10.1152/ajpendo.00009.2016. Epub 2016 Jul 12.


Imeglimin is a promising new oral antihyperglycemic agent that has been studied in clinical trials as a possible monotherapy or add-on therapy to lower fasting plasma glucose and improve hemoglobin A1c (1-3, 9). Imeglimin was shown to improve both fasting and postprandial glycemia and to increase insulin secretion in response to glucose during a hyperglycemic clamp after 1-wk of treatment in type 2 diabetic patients. However, whether the β-cell stimulatory effect of imeglimin is solely or partially responsible for its effects on glycemia remains to be fully confirmed. Here, we show that imeglimin directly activates β-cell insulin secretion in awake rodents without affecting hepatic insulin sensitivity, body composition, or energy expenditure. These data identify a primary amplification rather than trigger the β-cell mechanism that explains the acute, antidiabetic activity of imeglimin.

Keywords: glucose-stimulated insulin secretion; imeglimin; β-cell.

MeSH terms

  • Animals
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Diet, High-Fat
  • Fasting
  • Glucose / metabolism
  • Glucose Clamp Technique
  • Hypoglycemic Agents / pharmacology*
  • Insulin / metabolism*
  • Insulin Resistance
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Postprandial Period
  • Rats
  • Rats, Sprague-Dawley
  • Triazines / pharmacology*


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Triazines
  • Glucose
  • imeglimin