Diabetes/metabolism research and reviews
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Diabetes Metab. Res. Rev. · Jan 2019
ReviewGlucagon-like peptide-1 receptor agonists in type 2 diabetes treatment: are they all the same?
Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are an important class of drugs with a well-established efficacy and safety profile in patients with type 2 diabetes mellitus. Agents in this class are derived from either exendin-4 (a compound present in Gila monster venom) or modifications of human GLP-1 active fragment. Differences among these drugs in duration of action (ie, short-acting vs long-acting), effects on glycaemic control and weight loss, immunogenicity, tolerability profiles, and administration routes offer physicians several options when selecting the most appropriate agent for individual patients. ⋯ The aim of this review is to discuss the differences between and similarities of GLP-1 RAs currently approved for clinical use, focusing particularly on the properties characterising the single short-acting and long-acting GLP-1 RAs rather than on their individual efficacy and safety profiles. The primary pharmacodynamic difference between short-acting (ie, exenatide twice daily and lixisenatide) and long-acting (ie, albiglutide, dulaglutide, exenatide once weekly, liraglutide, and semaglutide) GLP-1 RAs is that short-acting agents primarily delay gastric emptying (lowering postprandial glucose) and long-acting agents affect both fasting glucose (via enhanced glucose-dependent insulin secretion and reduced glucagon secretion in the fasting state) and postprandial glucose (via enhanced postprandial insulin secretion and inhibition of glucagon secretion). Other advantages of long-acting GLP-1 RAs include smaller fluctuations in plasma drug concentrations, improved gastrointestinal tolerability profiles, and simpler, more convenient administration schedules (once daily for liraglutide and once weekly for albiglutide, dulaglutide, the long-acting exenatide formulation, and semaglutide), which might improve treatment adherence and persistence.