Lipid-lowering efficacy of the PCSK9 inhibitor evolocumab (AMG 145) in patients with type 2 diabetes: a meta-analysis of individual patient data

This meta-analysis (3 RCT; n=2532) of patients with and without type 2 diabetes, showed evolocumab treatment over 12 weeks caused relative mean reductions in LDL-cholesterol concentration of 60% vs placebo for patients with diabetes and 66% for patients without diabetes.

In a related editorial, the author notes that the main limitation of this meta-analysis is the short duration of the included studies, precluding adequate assessment of possible side-effects caused by the drug. Furthermore, whether
PCSK9, which is also present in the pancreas, could affect glucose homeostasis, is a controversial issue.

 

The author concludes that “Because of their high cost (more than US$12 000 dollars per year in the USA), the absence of robust evidence for reduction of cardiovascular events, and the need to prove long-term safety, PCSK9 inhibitors should initially be reserved for patients who are at the highest risk of cardiovascular disease and whose hypercholesterolaemia persists despite the use of other lipid-lowering treatments (e.g. patients with familial hypercholesterolaemia or those who are statin intolerant).”

In DRAFT guidance NICE recommends evolocumab, alone or in combination with other lipid-lowering therapies, only at a dosage of 140mg every 2 weeks, for primary non-familial hypercholesterolaemia and primary heterozygous-familial hypercholesterolaemia with set restrictions.