title: Lixisenatide as add-on therapy to basal insulin.
abstract: Many patients with type 2 diabetes mellitus do not achieve target glycosylated hemoglobin A1c levels despite optimally titrated basal insulin and satisfactory fasting plasma glucose levels. Current evidence suggests that HbA1c levels are dictated by both basal glucose and postprandial glucose levels. This has led to a consensus that postprandial glucose excursions contribute to poor glycemic control in these patients. Lixisenatide is a once-daily, prandial glucagon-like peptide 1 (GLP-1) receptor agonist with a four-fold affinity for the GLP-1 receptor compared with native GLP-1. Importantly, lixisenatide causes a significant delay in gastric emptying time, an important determinant of the once-daily dosing regimen. An exendin-4 mimetic with six lysine residues removed at the C-terminal, lixisenatide has pronounced postprandial glucose-lowering effects, making it a novel incretin agent for use in combination with optimally titrated basal insulin. Lixisenatide exerts profound effects on postprandial glucose through established mechanisms of glucose-dependent insulin secretion and glucagon suppression in combination with delayed gastric emptying. This review discusses the likely place that lixisenatide will occupy in clinical practice, given its profound effects on postprandial glucose and potential to reduce glycemic variability.
authors.affiliation: Diabetes Department, University Hospital Llandough, Cardiff, UK.
authors.forename: Dominique Xavier
authors.initials: DX
authors.lastname: Brown
authors.affiliation: Diabetes Department, University Hospital Llandough, Cardiff, UK.
authors.forename: Emma Louise
authors.initials: EL
authors.lastname: Butler
authors.affiliation: Diabetes Department, University Hospital Llandough, Cardiff, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Evans
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D019518:Postprandial Period; D018027:Receptors, Glucagon / Q000819:agonists*; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D001786:Blood Glucose; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010455:Peptides; D018027:Receptors, Glucagon; C000593833:GLP1R protein, human; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor
keywords: GLP-1 receptor agonist; add-on therapy; insulin; lixisenatide; pharmacodynamics; postprandial glucose