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Metformin and the gastrointestinal tract
Laura J McCreight1, Clifford J Bailey2, Ewan R Pearson3
1Pearson Group, Division of Cardiovascular and Diabetes Medicine, School of Medicine, University of Dundee, Ninewells Hospital, Mailbox 12, Level 5, Dundee, DD1 9SY, UK.
Diabetologia
|January 19, 2016
Summary
Metformin
Area of Science:
- Pharmacology
- Gastroenterology
- Endocrinology
Background:
- Metformin is a first-line treatment for type 2 diabetes with a good safety profile.
- Its precise mechanisms of action and reasons for variable efficacy and side effects are not fully understood.
- While the liver is a known site of action, the gut is increasingly recognized as crucial.
Purpose of the Study:
- To review the passage of metformin through the gastrointestinal tract.
- To explore how gut interactions influence metformin's efficacy and side effects.
- To understand the link between gut physiology and metformin response.
Main Methods:
- Review of existing literature on metformin pharmacodynamics and pharmacokinetics in the gut.
- Analysis of studies investigating metformin's effects on intestinal glucose uptake, GLP-1, bile acids, and the microbiome.
- Examination of data on delayed-release metformin preparations and their gut-specific actions.
Main Results:
- Metformin influences intestinal glucose uptake, lactate production, GLP-1 concentrations, and bile acid pools.
- Alterations in the gut microbiome are associated with metformin's actions.
- Delayed-release metformin shows similar glycemic control with reduced systemic exposure, suggesting a gut-mediated effect.
Conclusions:
- Metformin's efficacy and tolerability are closely linked to its interactions within the gut.
- Understanding gut-specific metformin actions is key to optimizing treatment for type 2 diabetes.
- Gut-focused strategies may improve metformin response and reduce side effects like intolerance.
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