ReviewKeynotePCSK9 and diabetes: is there a link?

•Available evidence suggests a positive link between PCSK9 levels and T2DM incidence.•There is a scientific gap on the impact of PCSK9 inhibition on glycemic control.•Phase III trials revealed no effect of the PCSK9 inhibitor on the risk NODM risk.•Ongoing CVOT trials will answer all the questions on this possible association.

Diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) have emerged as effective low-density lipoprotein cholesterol-lowering compounds. Although the results of available epidemiological, preclinical, and clinical studies suggest a positive association of plasma PCSK9 levels with glycemic parameters and risk of type 2 DM (T2DM), genetic findings have shown contradictory results. Overall, the impact of PCSK9 inhibitors on glycemic control parameters in patients with DM remains unclear. Here, we assess the available evidence for the association of PCSK9 status with the incidence and control of DM in preclinical and clinical studies, and identify molecular mechanisms regulating PCSK9 expression in the diabetic state.