title: Lixisenatide reduces glycaemic variability in insulin-treated patients with type 2 diabetes.
abstract: Chronic hyperglycaemia and glucose variability are associated with the development of chronic diabetes-related complications. We conducted a pooled analysis of patient-level data from three 24-week, randomized, phase III clinical trials to evaluate the impact of lixisenatide (LIXI) on glycaemic variability (GV) vs placebo as add-on to basal insulin. The main outcome GV measures were standard deviation (s.d.), mean amplitude of glycaemic excursions (MAGE), mean absolute glucose (MAG) level, area under the curve for fasting glucose (AUC-F), and high (HBGI) and low blood glucose index (LBGI). The change in GV metrics over 24 weeks and relationships among baseline GV, patient characteristics and outcomes were assessed. Data were pooled from 1198 patients (665 LIXI, 533 placebo). Values for s.d., MAG level, MAGE, HBGI, and AUC-F significantly decreased with LIXI vs placebo, while LBGI values were unchanged. Higher baseline GV measures correlated with older age, longer type 2 diabetes duration, lower body mass index, higher baseline glycated/haemogobin, greater reduction in postprandial glucose (PPG) level, and higher rates of symptomatic hypoglycaemia. These data show that LIXI added to basal insulin significantly reduced GV and PPG excursions vs placebo, without increasing the risk of hypoglycaemia (LBGI).
authors.affiliation: Department of Medicine, Emory University of Medicine, Atlanta, Georgia.
authors.forename: Guillermo E
authors.identifier: 0000-0002-3252-5026
authors.initials: GE
authors.lastname: Umpierrez
authors.affiliation: University of Melbourne, Department of Medicine, St Vincent's Hospital, Melbourne, Australia.
authors.forename: David
authors.initials: D
authors.lastname: O'Neal
authors.affiliation: AKCEA Therapeutics, Cambridge, Massachusetts.
authors.forename: Andres
authors.initials: A
authors.lastname: DiGenio
authors.affiliation: LMC Diabetes and Endocrinology, Thornhill, Ontario, Canada.
authors.forename: Ronald
authors.initials: R
authors.lastname: Goldenberg
authors.affiliation: Endocare Research Institute, Universidad del Rosario, Bogota, Colombia.
authors.forename: Eric
authors.initials: E
authors.lastname: Hernandez-Triana
authors.affiliation: Novosys Health, Green Brook, New Jersey.
authors.forename: Jay
authors.initials: J
authors.lastname: Lin
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Cheol-Young
authors.identifier: 0000-0002-9415-9965
authors.initials: CY
authors.lastname: Park
authors.affiliation: Department of Endocrinology, Diabetes, Nutrition, Montpellier University Hospital, Montpellier, France.|INSERM Clinical Investigation Centre 1411, Montpellier, France.|Institute of Functional Genomics, CNRS UMR 5203, INSERM U1191, University of Montpellier, Montpellier, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Renard
authors.affiliation: Center for Diabetes Technology, University of Virginia Health System, Charlottesville, Virginia.
authors.forename: Boris
authors.initials: B
authors.lastname: Kovatchev
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D015190:Blood Glucose Self-Monitoring; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005500:Follow-Up Studies; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology / Q000517:prevention & control*; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D057194:Intention to Treat Analysis; D008875:Middle Aged; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; D000067758:Glucagon-Like Peptide-2 Receptor
chemical_list: D001786:Blood Glucose; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C000593833:GLP1R protein, human; C517652:hemoglobin A1c protein, human; C479460:lixisenatide; D000067758:Glucagon-Like Peptide-2 Receptor
keywords: glycaemic variability; insulin; lixisenatide; type 2 diabetes