Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 28530702 · doi:10.1038/nm.4345
What was done
Individuals with treatment-naive type 2 diabetes were randomized to receive placebo or metformin for 4 months in a double-blind study. Findings were further evaluated in a subset of the placebo group that crossed over to metformin 6 months after trial initiation. Fecal samples collected before and 4 months after treatment were transplanted into germ-free mice to assess effects on glucose tolerance. Direct interactions between metformin and microbiota were also tested in a gut simulator across species from two phyla.
What was found
Metformin caused substantial alterations in the gut microbiome. Fecal microbiota transfer from metformin-treated human donors improved glucose tolerance in germ-free mice. In the gut simulator, metformin affected functional pathways across species from two phyla, altering genes encoding metalloproteins and metal transporters. No specific numerical values, effect sizes, or p-values were reported in the abstract.
Why it matters
This study provides evidence that metformin's therapeutic effects on glucose regulation are mediated in part by changes in the composition and function of the gut microbiota.
Limits
The abstract does not report the number of human participants, the number of mice, or quantitative effect sizes. In addition, mechanistic gut simulator findings and rodent fecal transplants may not fully replicate human in vivo physiology.
Cited by
- supports Metformin induces changes in the composition of the gut microbiome that contribute to its glucose-lowering effects in type 2 diabetes.