Mixed
Metformin increases circulating short-chain fatty acids (SCFAs), specifically acetate, butyrate, and valerate, at 6 months, which correlates with decreased fasting insulin, although these SCFA increases do not persist at 12 months.
Metformin boosts beneficial gut byproducts called short-chain fatty acids (SCFAs) like acetate and butyrate within the first 6 months, which is linked to better insulin control. However, this boost in SCFAs tends to fade after a year, even though the gut bacteria themselves remain changed. This suggests the body adapts to the higher SCFA levels, but the underlying microbial environment remains altered. This adaptation doesn't necessarily mean the drug stops working, but it highlights that the initial metabolic boost might be transient.
Metformin versus control also increased butyrate, acetate, and valerate at 6 months (but not at 12 months)... Increases in acetate were associated with decreases in fasting insulin.
Why this rating
RCT design with serum measurements, but the effect is transient and the mechanism for waning is speculative.
Source
Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized Trial
Noel T. Mueller et al. · Diabetes Care · 2021
DOI 10.2337/dc20-2257
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