Involvement of glucagon-like peptide-1 in the glucose-lowering effect of metformin.
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.
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Emilie
E
Bahne
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Morten
M
Hansen
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Andreas
A
Brønden
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
David P
DP
Sonne
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Tina
T
Vilsbøll
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. filipknop@dadlnet.dk.|NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. filipknop@dadlnet.dk.
Filip K
FK
Knop
D001647:Bile Acids and Salts / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D054795:Incretins / Q000627:therapeutic use; D008687:Metformin / Q000494:pharmacology*
D001647:Bile Acids and Salts; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D054795:Incretins; D052216:Glucagon-Like Peptide 1; D008687:Metformin
DPP-IV inhibitor; GLP-1; antidiabetic drug; drug mechanism; incretin therapy; metformin