title: No effect of PCSK9 inhibitor alirocumab on the incidence of diabetes in a pooled analysis from 10 ODYSSEY Phase 3 studies.
abstract: Statins have modest adverse effects on glycaemic control. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers low-density lipoprotein cholesterol. This study assessed the effects of alirocumab on new-onset diabetes and pre-diabetes incidence in individuals without diabetes at baseline.
  
  
  
  Pooled analysis of 10 ODYSSEY Phase 3 trials (n = 4974) of 24-104 weeks duration. Six trials (n = 4211) were ≥52 weeks in length. Most patients received background maximally tolerated statin. Alirocumab effect on the rate of diabetes-related treatment-emergent adverse events (TEAEs), and/or fasting plasma glucose (FPG) and glycated haemoglobin A1C(HbA1C) was measured at baseline and every 12-24 weeks. Transition to diabetes analysis combined TEAE and FPG/HbA1Claboratory data. At baseline, 30.7% of individuals had diabetes and were excluded from the current analysis. The remaining 3448 individuals without diabetes had pre-diabetes (39.6%) or were normoglycaemic (29.7%). The hazard ratio (HR; 95% confidence interval) for diabetes-related TEAEs in alirocumab was 0.64 (0.36-1.14) vs. placebo and 0.55 (0.22-1.41) vs. ezetimibe. The HR associated for transition from pre-diabetes to new-onset diabetes for alirocumab was 0.90 (0.63-1.29) vs. placebo and 1.10 (0.57-2.12) vs. ezetimibe. Mean change in FPG/HbA1Cover time showed no difference between treatment groups in patients without diabetes.
  
  
  
  There was no evidence of an effect of alirocumab on transition to new-onset diabetes in 3448 individuals without diabetes at baseline with a follow-up period of 6-18 months, compared to either placebo or ezetimibe. Longer follow-up with larger number of individuals is needed to conclusively rule out an effect.
authors.affiliation: University of Edinburgh, Edinburgh, UK helen.colhoun@igmm.ed.ac.uk.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Colhoun
authors.affiliation: Columbia University, New York, NY, USA.
authors.forename: Henry N
authors.initials: HN
authors.lastname: Ginsberg
authors.affiliation: University of Iowa, Iowa City, IA, USA.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Robinson
authors.affiliation: Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Leiter
authors.affiliation: University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, Aachen University, Aachen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Müller-Wieland
authors.affiliation: University of California San Diego School of Medicine, La Jolla, CA, USA.|Center for Metabolic Research, Veterans Affairs, San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Henry
authors.affiliation: CHU Nantes, Institut du Thorax, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Cariou
authors.affiliation: Sanofi, Montpellier, France.
authors.forename: Marie T
authors.initials: MT
authors.lastname: Baccara-Dinet
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, NY, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Pordy
authors.affiliation: Sanofi, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Merlet
authors.affiliation: University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Eckel
mesh_terms: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL; D003920:Diabetes Mellitus; D004791:Enzyme Inhibitors; D006801:Humans; D006937:Hypercholesterolemia; D015994:Incidence; D000071449:Proprotein Convertase 9
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL; D004791:Enzyme Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C571059:alirocumab
keywords: Diabetes; Fasting plasma glucose; Glycaemia; HbA1C; Low-density lipoprotein cholesterol; PCSK9 inhibitor