User’s guide to mechanism of action and clinical use of GLP-1 receptor agonists

Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are injectable glucose-lowering medications approved for the treatment of adult patients with type 2 diabetes mellitus (T2DM). This article provides practical information to guide primary care physicians on the use of GLP-1RAs in patients with T2DM. Two short-acting (once- or twice-daily administration; exenatide and liraglutide) and three long-acting (weekly administration; albiglutide, dulaglutide and exenatide) GLP-1RAs are currently approved in the US. These drugs provide levels of GLP-1 receptor agonism many times that of endogenous GLP-1. The GLP-1RAs have been shown to significantly improve glycemic parameters and reduce body weight. These agents work by activating GLP-1 receptors in the pancreas, which leads to enhanced insulin release and reduced glucagon release—responses that are both glucose-dependent—with a consequent low risk for hypoglycemia. Effects on GLP-1 receptors in the CNS and the gastrointestinal tract cause reduced appetite and delayed glucose absorption due to slower gastric emptying. The most common adverse effects are gastrointestinal, which are transient and less common with the long-acting drugs. GLP-1RAs are recommended as second-line therapy in combination with metformin, sulfonylureas, thiazolidinediones or basal insulin, providing a means of enhancing glucose control while offsetting the weight gain associated with insulin and some oral agents. GLP-1RAs represent a useful tool that the primary care physician can use to help patients with T2DM achieve their therapeutic goals.

Keywords:

• Glucagons
• glucagon-like peptide-1
• insulin
• receptor agonist
• type 2 diabetes mellitus

Declaration of interest

Lisa M. Klumpp Callan, PhD, CMPP, of inScience Communications, Springer Healthcare and Michael R. Jones, PhD, on behalf of inScience Communications, Springer Healthcare, provided medical writing support, funded by AstraZeneca. CF Shaefer, Jr. has served as a speaker and consultant for Bristol-Myers Squibb/AstraZeneca, Janssen, Lilly/Boehringer Ingelheim, Sanofi USA and Vivus. He has also served as a consultant for Sanofi global and as a speaker for Takeda. P Kushner has served as a speaker for Bristol-Myers Squibb/AstraZeneca and Eli Lilly/Pfizer. R Aguilar has served as a speaker and as an Advisory Board member for Boehringer Ingelheim, Eli Lilly, Janssen and Takeda Pharmaceuticals of America. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.