title: Differential effects of GLP-1 receptor agonists on components of dysglycaemia in individuals with type 2 diabetes mellitus.
abstract: Metabolic consequences of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are the result of enhanced glucose-stimulated insulin secretion, inhibition of glucagon release, delayed gastric emptying and increased satiety. These attributes make GLP-1 agonists a treatment option in type 2 diabetes mellitus (T2DM). To optimise treatment choice, a detailed understanding of the effects of GLP-1 RAs on glucose homeostasis in individuals with T2DM is necessary. Although the various GLP-1 RAs share the same basic mechanisms of action, differences in pharmacokinetic/pharmacodynamic characteristics translate into differential effects on parameters of glycaemia. Head-to-head comparisons between long-acting non-prandial (liraglutide once daily and exenatide once weekly) and shorter-acting prandial (exenatide twice daily and lixisenatide once daily prandial) GLP-1 RAs confirm their differential effects on fasting plasma glucose (FPG) and post-prandial glucose (PPG). Liraglutide once daily and exenatide once weekly demonstrate greater reductions in FPG but lesser impacts on PPG excursions plasma than exenatide twice daily. Prandial GLP-1 RAs have a profound effect on post-prandial glycaemia, mediated by delaying gastric emptying, which is not subject to the tachyphylaxis occurring due to the sustained elevated plasma GLP-1 concentrations after treatment with long-acting GLP-1 RAs. Lixisenatide once-daily prandial, in contrast to liraglutide, strongly suppresses post-prandial glucagon secretion, further contributing to the more pronounced PPG-lowering effect found with lixisenatide. Evidence suggests that the GLP-1 RAs that predominantly target the prandial glucose excursions, such as exenatide twice daily and lixisenatide once-daily prandial, are therefore best used as combination therapy with basal insulin and will form an important new treatment option for individuals with T2DM.
authors.affiliation: Diabetes Research Group, Institute of Life Sciences College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK. Electronic address: owensdr@cf.ac.uk.
authors.forename: D R
authors.initials: DR
authors.lastname: Owens
authors.forename: L
authors.initials: L
authors.lastname: Monnier
authors.forename: G B
authors.initials: GB
authors.lastname: Bolli
mesh_terms: D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage; D000069450:Liraglutide; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology; D018027:Receptors, Glucagon / Q000819:agonists*; D014688:Venoms / Q000008:administration & dosage; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D001786:Blood Glucose; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069450:Liraglutide; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; C000593833:GLP1R protein, human; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor
keywords: Agonistes des récepteurs du GLP-1; Diabète sucré de type 2; Effet prandial; GLP-1 receptor agonists; Incretin; Incrétine; Prandial; Type 2 diabetes mellitus