Involvement of glucagon-like peptide-1 in the glucose-lowering effect of metformin

TY - JOUR

T1 - Involvement of glucagon-like peptide-1 in the glucose-lowering effect of metformin

AU - Bahne, Emilie

AU - Hansen, Morten

AU - Brønden, Andreas

AU - Sonne, David P

AU - Lauritsen, Tina Vilsbøll

AU - Knop, Filip K

N1 - © 2016 John Wiley & Sons Ltd.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Metformin is an oral antihyperglycaemic drug used in the first-line treatment of type 2 diabetes. Metformin's classic and most well-known blood glucose-lowering mechanisms include reduction of hepatic gluconeogenesis and increased peripheral insulin sensitivity. Interestingly, intravenously administered metformin is ineffective and recently, metformin was shown to increase plasma concentrations of the glucose-lowering gut incretin hormone glucagon-like peptide-1 (GLP-1), which may contribute to metformin's glucose-lowering effect in patients with type 2 diabetes. The mechanisms behind metformin-induced increments in GLP-1 levels remain unknown, but it has been hypothesized that metformin stimulates GLP-1 secretion directly and/or indirectly and that metformin prolongs the half-life of GLP-1. Also, it has been suggested that metformin may potentiate the glucose-lowering effects of GLP-1 by increasing target tissue sensitivity to GLP-1. The present article critically reviews the possible mechanisms by which metformin may affect GLP-1 levels and sensitivity and discusses whether such alterations may constitute important and clinically relevant glucose-lowering actions of metformin.

AB - Metformin is an oral antihyperglycaemic drug used in the first-line treatment of type 2 diabetes. Metformin's classic and most well-known blood glucose-lowering mechanisms include reduction of hepatic gluconeogenesis and increased peripheral insulin sensitivity. Interestingly, intravenously administered metformin is ineffective and recently, metformin was shown to increase plasma concentrations of the glucose-lowering gut incretin hormone glucagon-like peptide-1 (GLP-1), which may contribute to metformin's glucose-lowering effect in patients with type 2 diabetes. The mechanisms behind metformin-induced increments in GLP-1 levels remain unknown, but it has been hypothesized that metformin stimulates GLP-1 secretion directly and/or indirectly and that metformin prolongs the half-life of GLP-1. Also, it has been suggested that metformin may potentiate the glucose-lowering effects of GLP-1 by increasing target tissue sensitivity to GLP-1. The present article critically reviews the possible mechanisms by which metformin may affect GLP-1 levels and sensitivity and discusses whether such alterations may constitute important and clinically relevant glucose-lowering actions of metformin.

KW - Journal Article

KW - Review

U2 - 10.1111/dom.12697

DO - 10.1111/dom.12697

M3 - Review

C2 - 27265206

SN - 1462-8902

VL - 18

SP - 955

EP - 961

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 10

ER -