title: Lipid-lowering efficacy and safety of alirocumab in patients with or without diabetes: A sub-analysis of ODYSSEY COMBO II.
abstract: This sub-analysis of the ODYSSEY COMBO II study compared the effects of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in high cardiovascular risk patients with or without diabetes mellitus (DM) receiving maximally tolerated statin therapy.
  
  
  
  COMBO II was a 104-week, double-blind study (n = 720) enrolling patients with documented atherosclerotic cardiovascular disease (ASCVD) and baseline LDL-C ≥70 mg/dL (1.8 mmol/L), and patients without documented ASCVD at high cardiovascular risk with LDL-C ≥100 mg/dL (2.6 mmol/L). Patients receiving maximally tolerated statin therapy were randomized (2:1) to alirocumab 75 mg every 2 weeks (Q2W; 1 mL subcutaneous injection) or oral ezetimibe 10 mg daily. Alirocumab dose was increased to 150 mg Q2W (also 1 mL) at Week 12 if Week 8 LDL-C was ≥70 mg/dL.
  
  
  
  History of DM was reported in 31% (n = 148) of patients on alirocumab and 32% (n = 77) of patients on ezetimibe. At Week 24, alirocumab consistently reduced LDL-C from baseline in patients with (-49.1%) or without DM (-51.2%) to a significantly greater extent than ezetimibe (-18.4% and -21.8%, respectively). Occurrence of treatment-emergent adverse events was similar between groups. Efficacy results at 104 weeks were similar to those at 24 weeks.
  
  
  
  Over a 104-week double-blind study period, alirocumab provided consistently greater LDL-C reductions than ezetimibe, with similar LDL-C results in patients with or without DM. Safety of alirocumab was similar regardless of baseline DM status.
authors.affiliation: Li Ka Shing Knowledge Institute and Keenan Research Center for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto, Canada.
authors.forename: Lawrence A
authors.identifier: 0000-0002-1040-6229
authors.initials: LA
authors.lastname: Leiter
authors.affiliation: Hospital Universitario Ramon y Cajal, University Alcala de Henares, Madrid, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Zamorano
authors.affiliation: Sanofi, Paris, France.
authors.forename: Maja
authors.initials: M
authors.lastname: Bujas-Bobanovic
authors.affiliation: Regeneron Pharmaceuticals, Tarrytown, New York.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Louie
authors.affiliation: Sanofi, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lecorps
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.affiliation: Metabolic Institute of America, Tarzana, California.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Handelsman
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D003131:Combined Modality Therapy / Q000009:adverse effects; D048909:Diabetes Complications / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control / Q000628:therapy; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D000070497:Healthy Lifestyle; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000628:therapy; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D000091362:PCSK9 Inhibitors; D012307:Risk Factors; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D000091362:PCSK9 Inhibitors; D015842:Serine Proteinase Inhibitors; C571059:alirocumab
keywords: cardiovascular disease; clinical trial; dyslipidaemia; type 1 diabetes; type 2 diabetes