Current understanding of metformin effect on the control of hyperglycemia in diabetes

J Endocrinol. 2016 Mar;228(3):R97-106. doi: 10.1530/JOE-15-0447. Epub 2016 Jan 7.

Abstract

Metformin is a first-line oral anti-diabetic agent that has been used clinically to treat patients with type 2 diabetes for over 60 years. Due to its efficacy in therapy and affordable price, metformin is taken by more than 150 million people each year. Metformin improves hyperglycemia mainly through the suppression of hepatic gluconeogenesis along with the improvement of insulin signaling. However, its mechanism of action remains partially understood and controversial, especially in regard to the role of AMPK in metformin's action and the mechanism of AMPK activation. In this review, we discuss recent advances in the understanding of metformin's suppression of hepatic glucose production and the mechanism related to the improvement of insulin signaling.

Keywords: glucose metabolism; insulin action; liver; metabolism.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • AMP-Activated Protein Kinases / physiology
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Enzyme Inhibitors
  • Gastrointestinal Microbiome / drug effects
  • Gluconeogenesis / drug effects
  • Glucose / metabolism
  • Glycerolphosphate Dehydrogenase / antagonists & inhibitors
  • Humans
  • Hyperglycemia / drug therapy*
  • Hypoglycemic Agents*
  • Insulin / metabolism
  • Liver / metabolism
  • Metformin / pharmacology*
  • Metformin / therapeutic use*
  • Signal Transduction / drug effects

Substances

  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Insulin
  • Metformin
  • Glycerolphosphate Dehydrogenase
  • AMP-Activated Protein Kinases
  • Glucose