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

Abstract

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.