Involvement of Glucagon-Like peptide-1 in the Glucose-Lowering Effect of Metformin

Diabetes Obes Metab. 2016 Oct;18(10):955-61. doi: 10.1111/dom.12697. Epub 2016 Jul 13.


Metformin is an oral antihyperglycaemic drug used in the first-line treatment of type 2 diabetes. Metformin's classic and most well-known blood glucose-lowering mechanisms include reduction of hepatic gluconeogenesis and increased peripheral insulin sensitivity. Interestingly, intravenously administered metformin is ineffective and recently, metformin was shown to increase plasma concentrations of the glucose-lowering gut incretin hormone glucagon-like peptide-1 (GLP-1), which may contribute to metformin's glucose-lowering effect in patients with type 2 diabetes. The mechanisms behind metformin-induced increments in GLP-1 levels remain unknown, but it has been hypothesized that metformin stimulates GLP-1 secretion directly and/or indirectly and that metformin prolongs the half-life of GLP-1. Also, it has been suggested that metformin may potentiate the glucose-lowering effects of GLP-1 by increasing target tissue sensitivity to GLP-1. The present article critically reviews the possible mechanisms by which metformin may affect GLP-1 levels and sensitivity and discusses whether such alterations may constitute important and clinically relevant glucose-lowering actions of metformin.

Keywords: DPP-IV inhibitor; GLP-1; antidiabetic drug; drug mechanism; incretin therapy; metformin.

Publication types

  • Review

MeSH terms

  • Bile Acids and Salts / metabolism
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy
  • Gastrointestinal Microbiome / drug effects
  • Glucagon-Like Peptide 1 / blood
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide 1 / physiology*
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Incretins / therapeutic use
  • Metformin / pharmacology*


  • Bile Acids and Salts
  • Blood Glucose
  • Hypoglycemic Agents
  • Incretins
  • Glucagon-Like Peptide 1
  • Metformin