Metformin use at doses approximating clinical levels shifts the NAD+/NADH ratio in the desired direction (towards NAD+).

“the mechanism of metformin is super interesting so people think that it's a complex one inhibitor but it doesn't inhibit complex one at physiologic concentrations it actually does this it's like really deep biochemistry so it's glycerophosphate dehydrogenase which is a part of the it's a part it's after glycolysis that regenerates nadh in the early steps of glycolysis like that's what metformin appears to inhibit”

“the effects that i do think are clinically relevant that we have observed at 50 and 100 micromolar of metformin are really on the enzyme glycerol 3-phosphate dehydrogenase the mitochondrial isoform that is required to move the protons from outside to inside the mitochondria and when you inhibit this enzyme nadh goes up nad goes down when you have this increase in the cytosolic redox you can't get lactate to pyruvate and you can't get glycerol to dhap”

“what we've shown both in vitro and in vivo most importantly in vivo in two or three different models metformin at these clinically relevant doses and concentrations only inhibit gluconeogenesis from glycerol and lactate it doesn't inhibit it from alanine or dhap or anything that does not depend on the cytosolic redox state”

“it's certainly crystal clear that it goes in the right direction”