Metformin and the gastrointestinal tract

Laura J. McCreight, Clifford J. Bailey, Ewan R. Pearson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Metformin is an effective agent with a good safety profile that is widely used as a first-line treatment for type 2 diabetes, yet its mechanisms of action and variability in terms of efficacy and side effects remain poorly understood. Although the liver is recognised as a major site of metformin pharmacodynamics, recent evidence also implicates the gut as an important site of action. Metformin has a number of actions within the gut. It increases intestinal glucose uptake and lactate production, increases GLP-1 concentrations and the bile acid pool within the intestine, and alters the microbiome. A novel delayed-release preparation of metformin has recently been shown to improve glycaemic control to a similar extent to immediate-release metformin, but with less systemic exposure. We believe that metformin response and tolerance is intrinsically linked with the gut. This review examines the passage of metformin through the gut, and how this can affect the efficacy of metformin treatment in the individual, and contribute to the side effects associated with metformin intolerance.

Original languageEnglish
Pages (from-to)426-435
Number of pages10
JournalDiabetologia
Volume59
Issue number3
Early online date16 Jan 2016
DOIs
Publication statusPublished - 1 Mar 2016

Bibliographical note

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Funding: Wellcome Trust New Investigator Award.

Keywords

  • bile acids
  • DPP-4
  • GLP-1
  • gut
  • lactate
  • metformin
  • microbiome
  • OCT1
  • review
  • serotonin
  • uptake
  • intestine

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