Does metformin (metformin hydrochloride) possess prebiotic properties?

From the Guidelines

Metformin does appear to have prebiotic qualities, as it can positively influence gut microbiota composition by promoting the growth of beneficial bacteria such as Akkermansia muciniphila and certain short-chain fatty acid-producing bacteria, as suggested by research 1.

Key Points

• Metformin's prebiotic effects may contribute to its therapeutic effects beyond blood glucose control, including improvements in metabolic parameters and potential reductions in cardiovascular risk.
• The medication typically works at standard therapeutic doses (500-2000 mg daily) to produce these effects, though they develop gradually over weeks to months of treatment 1.
• The prebiotic action occurs as metformin passes through the gastrointestinal tract, where a significant portion remains unabsorbed and can interact directly with gut bacteria, as noted in studies on metformin's mechanism of action 1.
• These microbiome changes appear to be an important mechanism through which metformin exerts its beneficial effects on glucose metabolism and overall metabolic health, highlighting the potential for metformin to have a positive impact on the gut microbiome and overall health 1.

Important Considerations

• Metformin is generally well-tolerated, but gastrointestinal side effects such as bloating, abdominal discomfort, and diarrhea can occur, particularly when starting the medication, as reported in studies on metformin's safety and efficacy 1.
• The risk of lactic acidosis with metformin is very rare, and the medication can be safely used in patients with reduced estimated glomerular filtration rates (eGFR) ≥30 mL/min/1.73 m², as indicated by recent guidelines and studies 1.
• Periodic testing of vitamin B12 levels may be necessary for patients taking metformin, as the medication has been associated with vitamin B12 deficiency and worsening of symptoms of neuropathy, as noted in recent research and guidelines 1.

From the Research

Metformin and Prebiotic Qualities

• Metformin has been found to alter the gut microbiota composition in several studies, suggesting that it may have prebiotic qualities 2, 3, 4, 5, 6.
• The changes in gut microbiota composition caused by metformin include an increase in the proportions of certain microbiota, such as phyla Bacteroidetes and Verrucomicrobia, and genera Akkermansia, Bacteroides, and Escherichia 2, 3, 4.
• Metformin may exert its hypoglycemic effects by altering the gut microbiota in ways that maintain the integrity of the intestinal barrier, promote the production of short-chain fatty acids (SCFAs), regulate bile acid metabolism, and improve glucose homeostasis 2, 3, 4, 5, 6.
• The gut microbiota of participants on metformin has been found to have an increased ability to produce butyrate and propionate, substances involved in glucose homeostasis 3.
• Metformin has been shown to directly affect the growth of certain bacteria, such as Akkermansia muciniphila and Bifidobacterium adolescentis, and to promote the production of SCFAs in the intestines 4, 5.

Key Findings

• Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug 5.
• The relationship between the gut microbiome and metformin is a key factor in treating type 2 diabetes mellitus 6.
• Metformin's mechanism of modulating glucose metabolism is elusive, but recent advances have identified the gut as a potential target of metformin 6.