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 trialLiterature - Leiter LA, Cariou B, Müller-Wieland D, et al. - Diabetes Obes Metab. 2017; published online ahead of print
- In the overall population, the primary efficacy endpoint of least squares (LS) mean (SE) % change in calculated LDL-C levels from baseline to week 24 was –50.1% (1.9%) for alirocumab and -1.3% (2.4%) for placebo, with a difference between groups of –48.8% (2.5%; P < 0.0001). In participants with T2DM, the difference between groups was –49.0% (2.7%; P < 0.0001) and –47.8% (6.5%; P < 0.0001) in those with T1DM.
- Alirocumab resulted in significant reductions from baseline to week 24 (difference vs placebo) in levels of non-HDL-C (–38.7%; P < 0.0001), apolipoprotein B (ApoB) (–36.7%; P < 0.0001), total cholesterol (–27.6%; P < 0.0001), and Lp(a) (–18.4%; P < 0.0001), as well as a significant increase in HDL-C (difference vs placebo 4.4%; P < 0.01).
- At week 24, the proportion of individuals achieving LDL-C <70 mg/dL was 76.4% in the alirocumab group and 7.4% in the placebo group (P < .0001), and the proportion of individuals attaining LDL-C of <50 mg/dL were 50.7% and 2.7% respectively (P < 0.0001).
- The proportion of patients with at least one TEAE was similar between the treatment groups. Treatment discontinuation due to a TEAE occurred in 4.9% in the alirocumab group and in 2.4% in the placebo group. TEAEs leading to discontinuation were headache, cognitive disorder, allergic dermatitis, and myalgia.
- In the T2DM population, 3.2% of alirocumab had treatment-emergent persistent anti-drug antibodies with a low-titer. The respective percentage for T1DM participants was 2.1%.
- The proportion of participants in the alirocumab group at weeks 12 and 24 with neutralizing anti-drug antibodies was 2.1% and 0.7% for the T2DM population, and 0% and 2% for the T1DM population, respectively.
- The participant-reported acceptability of subcutaneous injection of study treatment was high and showed no significant difference between treatment arms in perceived efficacy, acceptance of side effects, injection self-efficacy (confidence in self-injection), injection convenience, or overall acceptance for both the T2DM and T1DM populations.
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.