The Effect of Proprotein Convertase Subtilisin-Kexin Type 9 and its Inhibition on Glucose Metabolism and Cardiovascular Risk. We Should do Better the Second Time After Statins.

Background: Statins remain the cornerstone of hypolipidaemic drug treatment. However, statins exert adverse effects on glucose metabolism. Given that new onset diabetes mellitus (NODM) and worsening of glucose control in patients with established type 2 diabetes mellitus (T2DM) is related to low density lipoprotein cholesterol (LDL-C) reduction, it would be of great interest to investigate if this is also the case for proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, which have recently be licensed for the treatment of hypercholesterolaemia.

Methods: We reviewed the published papers on the relation between circulating PCSK9 and diabetogenesis.

Results: Recent data suggest that increased circulating PCSK9 levels, besides causing dyslipidaemia, are related to increased glucose levels, metabolic syndrome, and even T2DM. On the contrary, fasting plasma glucose and HbA1c levels are not adversely affected during treatment with human antibodies against PCSK9 in patients at low risk for T2DM, in patients at high risk of T2DM and in patients with established T2DM. Plasma lipoproteins (mainly LDL-C reduction) are similarly affected in patients with or without T2DM, and recent data suggest that PCSK9 inhibition might reduce cardiovascular events in patients with T2DM at least as much as in those without T2DM.

Conclusion: The use of PCSK9 inhibitors appears to be related to a substantial clinical benefit without adversely affecting glucose metabolism and without increasing the incidence of NODM. Large ongoing studies will have to confirm these findings before expanding the use of these agents.