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

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).