Efficacy and safety of alirocumab in insulin-treated individuals with type 1 or type 2 diabetes and high cardiovascular risk: The ODYSSEY DM-INSULIN randomized trial.
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
AIMS: To investigate efficacy and safety of alirocumab in participants with type 2 or type 1 diabetes treated with insulin and with elevated low-density lipoprotein cholesterol (LDL-C) despite maximally tolerated statin therapy. MATERIALS AND METHODS: Participants at high cardiovascular risk with type 2 (n = 441) or type 1 diabetes (n = 76) and LDL-C ≥70 mg/dL (≥1.8 mmol/L) were randomized 2:1 to alirocumab:placebo administered subcutaneously every 2 weeks (Q2W), for 24 weeks' double-blind treatment. Alirocumab-treated participants received a 75 mg Q2W dose, with blinded dose increase to 150 mg Q2W at week 12 if week 8 LDL-C ≥70 mg/dL. Primary endpoints were percentage change in calculated LDL-C from baseline to week 24, and safety assessments. RESULTS: Alirocumab reduced LDL-C from baseline to week 24 by (mean ± standard error) 49.0 ± 2.7% and 47.8 ± 6.5% vs placebo (both P<0.0001), in those with type 2 and type 1 diabetes, respectively. Significant reductions were observed in non-high-density-lipoprotein cholesterol (P<0.0001), apolipoprotein B (P<0.0001), and lipoprotein (a) (P≤0.0039). At week 24, 76.4% and 70.2% of the alirocumab group achieved LDL-C <70 mg/dL in the type 2 and type 1 diabetes populations (P<0.0001), respectively. Glycated haemoglobin and fasting plasma glucose levels remained stable for the study duration. Treatment-emergent adverse events were observed in 64.5% of alirocumab vs 64.1% of placebo treated individuals (overall population). CONCLUSIONS: Alirocumab produced significant LDL-C reductions in participants with insulin-treated diabetes regardless of diabetes type, and was generally well tolerated. Concomitant administration of alirocumab and insulin did not raise any safety concerns (NCT02585778).
Date Issued
2017-09-14
Date Acceptance
2017-09-01
Citation
Diabetes, Obesity and Metabolism, 2017, 19 (12), pp.1781-1792
ISSN
1462-8902
Publisher
Wiley
Start Page
1781
End Page
1792
Journal / Book Title
Diabetes, Obesity and Metabolism
Volume
19
Issue
12
Copyright Statement
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original
work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
© 2017 The Authors.
work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
© 2017 The Authors.
Subjects
cardiovascular disease
clinical trial
lipid-lowering therapy
type 1 diabetes
type 2 diabetes
1103 Clinical Sciences
Endocrinology & Metabolism
Publication Status
Published