Metformin is not an insulin sensitizer; perceived effects may be due to weight loss.

“what we showed was the insulin clamp the drug absolutely does not improve insulin sensitivity so let's talk about metformin everybody wants to know if metformin is geroprotective but let's just remind people um so so metformin inhibits complex one of the mitochondria is that of the electron transport chain is that a given uh yes uh in I I'd say this is still controversial okay in high doses for sure yes and the kind of doses you see with giving metformin I would say somewhat equivocal in my opinion so is it is the belief that metformin's efficacy in diabetes is through reducing hepatic glucose output that is 100% true okay and what's the mechanism by which it reduces hepatic glucose output inhibiting the mitochondrial chain in inhibiting glucano Genesis well for sure it inhibits glucano Genesis okay okay uh now uh metformin gets into cells through the organic cation transporter the organic cat iron transporter doesn't exist in muscle it can't possibly be an insulin sensitizer in muscle you're asking the drug to do something that's impossible and if you give labeled metformin does it get into muscle mitochondria no it doesn't get into muscle at all”