title: Efficacy and safety of alirocumab in insulin-treated patients with type 1 or type 2 diabetes and high cardiovascular risk: Rationale and design of the ODYSSEY DM-INSULIN trial.
abstract: OBJECTIVE
  The coadministration of alirocumab, a PCSK9 inhibitor for treatment of hypercholesterolaemia, and insulin in diabetes mellitus (DM) requires further study. Described here is the rationale behind a phase-IIIb study designed to characterize the efficacy and safety of alirocumab in insulin-treated patients with type 1 (T1) or type 2 (T2) DM with hypercholesterolaemia and high cardiovascular (CV) risk.
  
  
  METHODS
  ODYSSEY DM-INSULIN (NCT02585778) is a randomized, double-blind, placebo-controlled, multicentre study that planned to enrol around 400 T2 and up to 100 T1 insulin-treated DM patients. Participants had low-density lipoprotein cholesterol (LDL-C) levels at screening≥70mg/dL (1.81mmol/L) with stable maximum tolerated statin therapy or were statin-intolerant, and taking (or not) other lipid-lowering therapy; they also had established CV disease or at least one additional CV risk factor. Eligible patients were randomized 2:1 to 24weeks of alirocumab 75mg every 2weeks (Q2W) or a placebo. Alirocumab-treated patients with LDL-C≥70mg/dL at week 8 underwent a blinded dose increase to 150mg Q2W at week 12. Primary endpoints were the difference between treatment arms in percentage change of calculated LDL-C from baseline to week 24, and alirocumab safety.
  
  
  RESULTS
  This is an ongoing clinical trial, with 76 T1 and 441 T2 DM patients enrolled; results are expected in mid-2017.
  
  
  CONCLUSIONS
  The ODYSSEY DM-INSULIN study will provide information on the efficacy and safety of alirocumab in insulin-treated individuals with T1 or T2 DM who are at high CV risk and have hypercholesterolaemia not adequately controlled by the maximum tolerated statin therapy.
authors.affiliation: Institut du thorax, CHU Nantes, INSERM, CNRS, UNIV Nantes, 44093 Nantes cedex 1, France. Electronic address: bertrand.cariou@univ.nantes.fr.
authors.forename: B
authors.initials: B
authors.lastname: Cariou
authors.affiliation: Li KaShing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: L A
authors.initials: LA
authors.lastname: Leiter
authors.affiliation: Department of Internal Medicine I, University Hospital Aachen, Aachen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Müller-Wieland
authors.affiliation: IVIDATA, 92300 Levallois-Perret, France.
authors.forename: G
authors.initials: G
authors.lastname: Bigot
authors.affiliation: University of Edinburgh, Edinburgh, Scotland, UK.
authors.forename: H M
authors.initials: HM
authors.lastname: Colhoun
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Del Prato
authors.affiliation: University of California San Diego School of Medicine, Center for Metabolic Research, Veterans Affairs, San Diego Healthcare System, San Diego, CA, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Henry
authors.affiliation: CIBERobn, Hospital Virgen de la Victoria, Málaga University, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Tinahones
authors.affiliation: Sanofi, 91380 Chilly-Mazarin, France.
authors.forename: A
authors.initials: A
authors.lastname: Letierce
authors.affiliation: Sanofi, Bridgewater, NJ, USA.
authors.forename: L
authors.initials: L
authors.lastname: Aurand
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Maroni
authors.affiliation: Department of Primary Care and Public Health, School of Public Health, Imperial College, London, UK.
authors.forename: K K
authors.initials: KK
authors.lastname: Ray
authors.affiliation: Sanofi, 75008 Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Bujas-Bobanovic
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002318:Cardiovascular Diseases / Q000209:etiology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012107:Research Design; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007328:Insulin; C571059:alirocumab
keywords: Alirocumab; Diabetes; Insulin; LDL-C; ODYSSEY; PCSK9