Efficacy and safety of alirocumab in individuals with type 2 diabetes mellitus with or without mixed dyslipidaemia: Analysis of the ODYSSEY LONG TERM trial

• Published in: Atherosclerosis Vol. 276; pp. 124 - 130
• Main Authors: Taskinen, Marja-Riitta, Del Prato, Stefano, Bujas-Bobanovic, Maja, Louie, Michael J., Letierce, Alexia, Thompson, Desmond, Colhoun, Helen M.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.09.2018
• Subjects: Alirocumab; Cardiovascular risk; Cholesterol-lowering drugs; Low-density lipoprotein cholesterol; Proprotein convertase subtilisin/kexin type 9; Type 2 diabetes mellitus; Cholesterol-lowering drugs; Proprotein convertase subtilisin/kexin type 9; Alirocumab; Type 2 diabetes mellitus; Low-density lipoprotein cholesterol; Cardiovascular risk
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2018.07.017

Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, significantly reduces low-density lipoprotein cholesterol (LDL-C). We evaluated the efficacy and safety of alirocumab in individuals with type 2 diabetes mellitus (T2DM) with versus without mixed dyslipidaemia (MDL, defined as baseline LDL-C ≥70 mg/dL [1.8 mmol/L] and triglycerides ≥150 mg/dL [1.7 mmol/L]). Data from 812 individuals with T2DM, from the placebo-controlled, 78-week, Phase 3 ODYSSEY LONG TERM trial of alirocumab 150 mg every 2 weeks (Q2W), on a background of maximally tolerated statins ± other lipid-lowering therapies, were pooled according to MDL status. Efficacy endpoints included percentage change from baseline to Week 24 in calculated LDL-C and other lipids/lipoproteins. In individuals with T2DM who received alirocumab 150 mg Q2W, mean LDL-C changes from baseline to Week 24 were −62.6% (vs. −6.0% with placebo) in those with MDL and −56.1% (vs. 5.6%) in those without MDL, with no significant between-group difference (p-interaction = 0.0842). Risk-based LDL-C goals (<70 [1.8 mmol/L] or <100 mg/dL [2.6 mmol/L]) were achieved by 69.1% and 72.4% of alirocumab-treated individuals with and without MDL, respectively. Mean reductions in non-high-density lipoprotein cholesterol (49.2% and 47.8%) and apolipoprotein B (50.2% and 49.1%) with alirocumab were also similar in those with and without MDL, respectively. Treatment-emergent adverse event rates were comparable between alirocumab-treated individuals with T2DM, with and without MDL. Reductions in LDL-C and other lipids with alirocumab, as well as safety and tolerability, were comparable between individuals with T2DM and with versus without MDL. [Display omitted] •Individuals with T2DM and mixed dyslipidaemia (MDL) are at very high CV risk.•This is a subanalysis of LONG TERM, a Phase 3 randomized placebo-controlled trial.•In T2DM ± MDL alirocumab significantly reduced atherogenic lipid/lipoprotein levels.•Alirocumab's safety profile was favourable in subjects with T2DM with/without MDL.