Title: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
Volume: 23
Issue: 10
Author(s): Vasilios G. Athyros*, Konstantinos Tziomalos, Michael Doumas, George Sfikas and Asterios Karagiannis
Affiliation:
- Head of Metabolic Disease Units, 2nd Pop. Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocrates Hospital, Thessaloniki, Greece. 15 Marmara St, Thessaloniki, 55132,Greece
Keywords:
PCSK9 antibodies, dyslipidaemia, glucose metabolism, new onset diabetes, cardiovascular risk, statins.
Abstract: 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.
