Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials

Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9.

Abstract

Aim: To evaluate the safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab according to diabetes mellitus status.

Methods: Safety data from 14 trials (8-104-week durations) were analysed by treatment (alirocumab or placebo/ezetimibe control) and diabetes status (yes/no, defined by medical history). Adverse event data were assessed using descriptive statistics and Cox models.

Results: Of the 5234 trial participants, 1554 (29.7%) had diabetes. Overall, treatment-emergent adverse events were similar in the alirocumab and control groups, except for more frequent local injection site reactions with alirocumab. Fewer people with diabetes experienced local injection site reactions [alirocumab, 3.5%, control, 2.9%; hazard ratio 1.24 (95% CI 0.68-2.25)] than those without diabetes [alirocumab, 7.5%; control, 4.9%; hazard ratio 1.51 (95% CI 1.13-2.01)]. Those with diabetes reported a greater number of serious adverse events (alirocumab, 19.4%; control, 19.7%) than those without diabetes (alirocumab, 14.5%; control, 13.5%). In people with diabetes, major adverse cardiac events occurred in 2.7% of alirocumab-treated people [control, 3.3%; hazard ratio 0.74 (95% CI 0.41-1.35)]; in those without diabetes, 1.8% of alirocumab-treated people had major adverse cardiac events [control, 1.7%; hazard ratio 0.95 (95% CI 0.56-1.62)]. Overall, no increase in HbA1c or fasting plasma glucose vs control treatment groups was observed, regardless of diabetes status.

Conclusion: This pooled analysis across 14 trials demonstrated similar safety for alirocumab vs control treatment, irrespective of diabetes status, except for more frequent local injection site reactions with alirocumab. People with diabetes reported fewer local injection site reactions than those without diabetes.

Trial registration: ClinicalTrials.gov NCT01288443 NCT01288469 NCT01266876 NCT01812707 NCT01507831 NCT01617655 NCT01644175 NCT01623115 NCT01709500 NCT01644188 NCT01730040 NCT01730053 NCT01644474 NCT01709513.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Humanized
  • Clinical Trials, Phase II as Topic / statistics & numerical data*
  • Clinical Trials, Phase III as Topic / statistics & numerical data*
  • Diabetes Complications / blood
  • Diabetes Complications / drug therapy*
  • Diabetes Complications / epidemiology
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Female
  • Heart Diseases / chemically induced
  • Heart Diseases / epidemiology
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / complications
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / epidemiology
  • Incidence
  • Male
  • Middle Aged
  • Proprotein Convertase 9 / antagonists & inhibitors
  • Proprotein Convertase 9 / immunology
  • Randomized Controlled Trials as Topic / statistics & numerical data

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • alirocumab

Associated data

  • ClinicalTrials.gov/NCT01288443
  • ClinicalTrials.gov/NCT01288469
  • ClinicalTrials.gov/NCT01266876
  • ClinicalTrials.gov/NCT01812707
  • ClinicalTrials.gov/NCT01507831
  • ClinicalTrials.gov/NCT01617655
  • ClinicalTrials.gov/NCT01644175
  • ClinicalTrials.gov/NCT01623115
  • ClinicalTrials.gov/NCT01709500
  • ClinicalTrials.gov/NCT01644188
  • ClinicalTrials.gov/NCT01730040
  • ClinicalTrials.gov/NCT01730053
  • ClinicalTrials.gov/NCT01644474
  • ClinicalTrials.gov/NCT01709513