Efficacy and safety of proprotein convertase subtilisin/kexin 9 inhibitors in people with diabetes and dyslipidaemia

Abstract

Diabetic dyslipidaemia, characterized by quantitative, qualitative and kinetic changes in all major circulating lipids, contributes to the increased cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). A promising therapeutic avenue is the inhibition of the proprotein convertase subtilisin kexin 9 (PCSK9) with human monoclonal antibodies (mAbs) that potently reduce plasma low-density lipoprotein cholesterol (LDL-C) levels on top of statin treatment. The aim of this review is to evaluate the efficacy of PCSK9 inhibitors to lower the residual cardiovascular risk of T2DM patients and to discuss the safety of PCSK9 inhibition in these patients. PCSK9 inhibitors potently lower plasma LDL-C levels in T2DM patients and reduce risk for the development of cardiovascular disease. Anti-PCSK9 mAbs are generally not more or less effective in T2DM patients compared to a general high-risk population. Nevertheless, due to their higher cardiovascular risk, the absolute risk reduction of major cardiovascular events is more significant in T2DM patients. This suggests that treatment of T2DM patients with anti-PCSK9 mAbs could be attractive from a cost-effectiveness perspective. Treatment with anti-PCSK9 mAbs did not result in significant treatment-emergent adverse effects. While genetic studies suggest a potential link between PCSK9 inhibition and glucose homeostasis, anti-PCSK9 mAbs did not worsen glycaemic control in T2DM patients, but their safety should be verified after a longer-term follow-up.

Keywords: PCSK9 monoclonal antibodies; diabetes; dyslipidaemia; low-density lipoprotein cholesterol; low-density lipoprotein receptor; proprotein convertase subtilisin-kexin 9; statins.