Overview
- A Northwestern-led paper in Nature Metabolism, published Friday, finds the drug blocks mitochondrial complex I in the intestinal lining and pushes those cells to use extra glucose.
- In mice engineered to resist this mitochondrial block only in the gut, metformin lost much of its ability to lower blood sugar, showing the intestinal target is essential.
- Researchers report signals tied to this gut action in people on metformin, including lower citrulline and higher GDF15, lactate and Lac-Phe, which align with lower after-meal glucose.
- The team shows phenformin and the supplement berberine work through the same intestinal pathway, while noting berberine lacks the rigorous evidence behind approved drugs.
- The findings point to gut-directed diabetes therapies and revise decades of focus on the liver for a drug taken by millions.