Metformin inhibits intestinal mitochondrial complex I to lower blood glucose
Updated
Updated · Nature.com · May 8
Metformin inhibits intestinal mitochondrial complex I to lower blood glucose
7 articles · Updated · Nature.com · May 8
Nature Metabolism reported plasma metabolomics in metformin-treated humans and mechanistic mouse studies showing the drug acts selectively in the intestinal epithelium.
Researchers said this mechanism explains enhanced intestinal glucose use, improved post-meal glycaemic control, and increased production of GDF15 and N-lactoyl-phenylalanine.
The findings challenge the long-held emphasis on liver glucose production alone and help unify several previously observed clinical effects of the widely used type 2 diabetes drug.
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Metformin’s Gut-Centric Mechanism: How Intestinal Mitochondrial Inhibition Redefines Diabetes Treatment and Expands Therapeutic Horizons
Overview
Between 2024 and 2026, groundbreaking research has shifted our understanding of metformin’s action in type 2 diabetes. Instead of acting mainly on the liver, new evidence shows that metformin works primarily in the intestinal epithelium. This discovery comes from studies using advanced metabolomic data from humans and genetic tools in mice, giving a clearer picture of the drug’s mechanism at the cellular level. Metformin targets and inhibits mitochondrial complex I in the gut lining, which explains its therapeutic effects and several well-known clinical outcomes seen in patients. This gut-focused mechanism opens new directions for diabetes treatment.