No effect of PCSK9 inhibitor alirocumab on the incidence of diabetes in a pooled analysis from 10 ODYSSEY Phase 3 studies

• Published in: European heart journal Vol. 37; no. 39; pp. 2981 - 2989
• Main Authors: Colhoun, Helen M, Ginsberg, Henry N, Robinson, Jennifer G, Leiter, Lawrence A, Müller-Wieland, Dirk, Henry, Robert R, Cariou, Bertrand, Baccara-Dinet, Marie T, Pordy, Robert, Merlet, Laurence, Eckel, Robert H
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 14.10.2016
• Subjects: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Cholesterol, LDL; Clinical Research; Diabetes Mellitus; Editor's Choice; Enzyme Inhibitors; Humans; Hypercholesterolemia; Incidence; Proprotein Convertase 9; Glycaemia; PCSK9 inhibitor; Diabetes; Fasting plasma glucose; HbA1C; Low-density lipoprotein cholesterol
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehw292

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.