Longevity & AgingMetformin Lowers Blood Sugar Through the Gut, Muscle and Liver, Not Just the Liver
Metformin is the foundation of oral type 2 diabetes treatment, yet how it lowers blood sugar is still debated. This review in Pharmacological Reviews synthesizes evidence that the drug acts in several organs, not only the liver, where most research has focused. Clinical studies indicate that improved glucose uptake into skeletal muscle is at least as important as reduced liver glucose production. Gut effects also appear to matter: reduced glucose absorption, greater glucose transport into the colon, increased GLP-1 secretion that signals the liver through the gut-brain axis, and shifts in the microbiome and bile acids. The kidney may contribute by reducing glucose production. Inhibition of mitochondrial complex I in different tissues emerges as a possible unifying mechanism. Many liver findings, however, come from doses higher than those used in patients.
