The systemic implication of novel non-statin therapies in cardiovascular diabetology: PCSK9 as a case model

PCSK9, like other novel non-statin drugs were primarily developed to help patients achieve low-density lipoprotein cholesterol targets, especially in patients with dyslipidemia not achieving lipid goals with statins due to poor tolerance or inadequate response. PCSK9 inhibitors, in addition to modulating lipid metabolism, improve mortality outcomes in cardiovascular disease. These benefits are markedly pronounced in patients with type 2 diabetes mellitus. However, these benefits do not come without associated risk. Multiple trials, studies, and case reports have attempted to explain observed outcomes with PCSK9 expression and administration of PCSK9 inhibitors from multiple perspectives, such as their effects on insulin sensitivity and glucose tolerance, changes in renal physiology, thyroid physiology, vascular tone, intestinal regulation of lipids, and improved cardiovascular function. These agents represent an opportunity for physicians to exercise prudence by using appropriate clinical judgement when managing comorbidities in the hyperglycemic patient, a concept that extends to other novel non-statin drugs.