Metformin and the gastrointestinal tract

By L. McCreight, C. Bailey, E. Pearson. Diabetologia, 2016

658 citations recorded by the source corpus.

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.

Subfields: Endocrinology, Diabetes and Metabolism, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/ce49bcc91945be3d2706d0da1b1a41bdfc8bdcda

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In Endocrinology, Diabetes and Metabolism

In Molecular Biology

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Citations in the corpus

Benefits of Metformin in Attenuating the Hallmarks of Aging (2020, background): “Most of these minor side effects include gastrointestinal discomfort such as abdominal or stomach pain, early satiety, decreased appetite, and diarrhea, which usually subside after one or two weeks of use (McCreight et al. 2016).”
Cellular and Molecular Mechanisms of Metformin Action (2020, background): “…intolerance in ~5% of patients (76-78) In recent years, the clinical benefits of metformin have been linked to alterations in gut microbiome composition, intestinal glucose uptake, and hormone (eg, growth differentiation factor 15 [GDF15], glucagon-like peptide-1 [GLP-1]) secretion (44, 45, 79-82).”
Metformin: historical overview (2017, background): “Advances in pharmacogenomics may better inform responsiveness to metformin and effects on the gut microbiome, and animal studies have intriguingly noted anti-ageing effects of metformin [90, 91].”
The mechanisms of action of metformin (2017, background): “There are a number of putative mechanisms for how metformin could impact on glucose metabolism via actions on the intestines (reviewed in [40]).”