Alirocumab: No Effect on Incidence of Diabetes

Study Questions:

What are the effects of alirocumab on new-onset diabetes and prediabetes incidence in individuals without diabetes at baseline?


This was a pooled analysis of 10 main ODYSSEY Phase 3 randomized, double-blind, controlled trials (n = 4,974) with subcutaneous alirocumab dosing every 2 weeks. Patients were randomized to alirocumab, or to either placebo or to ezetimibe as comparators. Individuals were categorized as having diabetes, prediabetes, or being normoglycemic at baseline and follow-up. Effect on the rate of diabetes-related treatment-emergent adverse events (TEAEs) and/or fasting plasma glucose and glycated hemoglobin was measured at baseline and every 12-24 weeks.


Overall, across the studies, 30.7% had diabetes, 39.6% had prediabetes, and 29.7% were normoglycemic. The hazard ratio (HR; 95% confidence interval) for diabetes-related TEAEs in alirocumab was 0.64 (0.36-1.14) versus placebo and 0.55 (0.22-1.41) versus ezetimibe. The HR associated with transition from prediabetes to new-onset diabetes for alirocumab was 0.90 (0.63-1.29) versus placebo and 1.10 (0.57-2.12) versus ezetimibe.


Compared to either placebo or ezetimibe, there was no evidence of an effect of alirocumab on transition to new-onset diabetes in those without diabetes at baseline with a follow-up period of 6-18 months.


This is a valuable study, which demonstrates that the PCSK9 inhibitor alirocumab does not have an effect on diabetes incidence, despite the robust impact on low-density lipoprotein cholesterol lowering. As the authors caution, “As effects of statin on glycemic control were not suggested until data from larger outcome studies were available, longer follow-up with a larger number of individuals will be important to determine definitively the effect of PCSK9 inhibitors on the development of diabetes.” Of note, the majority of participants in the ODYSSEY program were already on background statin therapy; approximately 54% of the individuals in the pooled analysis were receiving high-dose background statin therapy.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Diet

Keywords: Blood Glucose, Cholesterol, LDL, Diabetes Mellitus, Dyslipidemias, Fasting, Hemoglobin A, Glycosylated, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Metabolic Syndrome X, Outcome Assessment (Health Care), Prediabetic State, Primary Prevention

< Back to Listings