Metabolic Effects of Metformin in Humans

Author(s): María M. Adeva-Andany* , Eva Rañal-Muíño , Carlos Fernández-Fernández , Cristina Pazos-García , Matilde Vila-Altesor .

Journal Name: Current Diabetes Reviews

Volume 15 , Issue 4 , 2019

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Background: Both insulin deficiency and insulin resistance due to glucagon secretion cause fasting and postprandial hyperglycemia in patients with diabetes.

Introduction: Metformin enhances insulin sensitivity, being used to prevent and treat diabetes, although its mechanism of action remains elusive.

Results: Patients with diabetes fail to store glucose as hepatic glycogen via the direct pathway (glycogen synthesis from dietary glucose during the post-prandial period) and via the indirect pathway (glycogen synthesis from “de novo” synthesized glucose) owing to insulin deficiency and glucagoninduced insulin resistance. Depletion of the hepatic glycogen deposit activates gluconeogenesis to replenish the storage via the indirect pathway. Unlike healthy subjects, patients with diabetes experience glycogen cycling due to enhanced gluconeogenesis and failure to store glucose as glycogen. These defects raise hepatic glucose output causing both fasting and post-prandial hyperglycemia. Metformin reduces post-prandial plasma glucose, suggesting that the drug facilitates glucose storage as hepatic glycogen after meals. Replenishment of glycogen store attenuates the accelerated rate of gluconeogenesis and reduces both glycogen cycling and hepatic glucose output. Metformin also reduces fasting hyperglycemia due to declining hepatic glucose production. In addition, metformin reduces plasma insulin concentration in subjects with impaired glucose tolerance and diabetes and decreases the amount of insulin required for metabolic control in patients with diabetes, reflecting improvement of insulin activity. Accordingly, metformin preserves β-cell function in patients with type 2 diabetes.

Conclusion: Several mechanisms have been proposed to explain the metabolic effects of metformin, but evidence is not conclusive and the molecular basis of metformin action remains unknown.

Keywords: Diabetes, glucose, GLUT2, insulin resistance, insulin, glucagon.

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Year: 2019
Page: [328 - 339]
Pages: 12
DOI: 10.2174/1573399814666181009125348
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