Journal article
No effect of PCSK9 inhibitor alirocumab on the incidence of diabetes in a pooled analysis from 10 ODYSSEY Phase 3 studies
European heart journal, Vol.37(39), pp.2981-2989
10/14/2016
DOI: 10.1093/eurheartj/ehw292
PMCID: PMC5081037
PMID: 27460890
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 A
(HbA
) was measured at baseline and every 12-24 weeks. Transition to diabetes analysis combined TEAE and FPG/HbA
laboratory 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/HbA
over 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.
Details
- Title: Subtitle
- No effect of PCSK9 inhibitor alirocumab on the incidence of diabetes in a pooled analysis from 10 ODYSSEY Phase 3 studies
- Creators
- Helen M Colhoun - University of Edinburgh, Edinburgh, UK helen.colhoun@igmm.ed.ac.ukHenry N Ginsberg - Columbia University, New York, NY, USAJennifer G Robinson - University of Iowa, Iowa City, IA, USALawrence A Leiter - Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, ON, CanadaDirk Müller-Wieland - University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, Aachen University, Aachen, GermanyRobert R Henry - Center for Metabolic Research, Veterans Affairs, San Diego Healthcare System, San Diego, CA, USABertrand Cariou - CHU Nantes, Institut du Thorax, FranceMarie T Baccara-Dinet - Sanofi, Montpellier, FranceRobert Pordy - Regeneron Pharmaceuticals, Tarrytown, NY, USALaurence Merlet - Sanofi, Paris, FranceRobert H Eckel - University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
- Resource Type
- Journal article
- Publication Details
- European heart journal, Vol.37(39), pp.2981-2989
- DOI
- 10.1093/eurheartj/ehw292
- PMID
- 27460890
- PMCID
- PMC5081037
- NLM abbreviation
- Eur Heart J
- ISSN
- 1522-9645
- eISSN
- 1522-9645
- Publisher
- England
- Grant note
- name: Sanofi and Regeneron Pharmaceuticals, Inc
- Language
- English
- Date published
- 10/14/2016
- Academic Unit
- Epidemiology; Internal Medicine
- Record Identifier
- 9983995179402771
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