Physicians' Academy for Cardiovascular Education

Clinical benefit of PCSK9 inhibition in diabetic patients on insulin at high CV risk

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

Leiter LA, Cariou B, Müller-Wieland D, et al. - Diabetes Obes Metab. 2017; published online ahead of print


LDL-C-lowering with statins, and in combination with ezetimibe, leads to significant reductions in CV events in diabetic patients [1]. Current guidelines recommend targeting an LDL-C goal of <70 mg/dL (1.8 mmol/L), or even <50 mg/dL (1.3 mmol/L), and/or a reduction of ≥50% from baseline, in subjects with T2DM or T1DM at high or very high CV risk [2-4]. However, a significant proportion of diabetic individuals do not reach target LDL-C levels in real-life studies, and are therefore exposed to a significant residual CV risk [5].

In the phase 3b randomized, double-blind, placebo-controlled, parallel-group, multicenter ODYSSEY DM-INSULIN study, the efficacy and safety of alirocumab, a PCSK9 inhibitor, was evaluated, in insulin-treated individuals with T1DM or T2DM at high CV risk, not reaching LDL-C goals despite maximum tolerated statin therapy, with or without other lipid-lowering therapies (LLTs).

The study consisted of a screening period of up to 3 weeks and a double-blind treatment period of 24 weeks, followed by a safety observation period of 8 weeks. 441 patients with T2DM and 76 patients with T1DM were randomized to alirocumab or placebo (2:1). Alirocumab was administered at a starting dose of 75 mg Q2W, with a blinded dose increase to 150 mg Q2W at week 12, if week 8 LDL-C levels were ≥70 mg/dL. Other LLT remained stable throughout the entire study.

Main results


The PCSK9-antibody alirocumab produced significant LDL-C reductions in individuals with hypercholesterolemia with either T2DM or T1DM at high CV risk receiving insulin treatment, with no apparent effect on overall safety or measures of glycemic control. These data show that the concomitant therapy with alirocumab and insulin is feasible.


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Find this article online at Diab Obesity Metab