Mechanisms Of Action In Humans Glucose Production

Accelerated endogenous glucose production is thought to be a key factor in the development of fasting hyperglycemia in type 2 diabetes (21,22). In patients with type 2 diabetes metformin has been shown to inhibit endogenous glucose production in most (23-29), but not all studies (summarized in Ref. 30) to various degrees (from a nonsignificant ~10% up to a significant ~30% (Fig. 4) (30). This could largely be accounted for by inhibition of gluconeogenesis (24,31) although an additional inhibitory effect of metformin on glycogen breakdown is likely (24,25). The observation in many studies that in the basal postabsorptive state overall glucose disposal (metabolic plasma clearance rate of glucose) did not change while endogenous glucose production decreased (23-25,28,29,32) suggests that the improvement in glycemic control is largely attributable to the effect of metformin on glucose production.

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