On the mechanism of action of biguanides. evidence against an inhibition of gluconeogenesis from protein in normal fasting subjects.

The effect of phenformin on fuel homeostasis and on gluconeogenesis from protein was studied in 8 normal subjects who underwent two 4-day fasts 8-12 weeks apart. Each person received placebo or phenformin 50 mg every 12 hours for 3 days before and during the fasts. Circulating glucose, lactate, pyruvate, free fatty acid and ketone levels as well as urinary nitrogen excretion observed during placebo and phenformin treatment were not significantly different from each other. The lack of an effect of phenformin on urinary nitrogen excretion and plasma glucose level strongly suggests that gluconeogenesis from amino acids was unaltered by phenformin in these fasting subjects. The present findings are at variance with those by other authors which may be related to differences in methodology.