Dyslipidemia in Diabetes: Navigating a Complex Landscape for Improved Cardiovascular Outcomes.

Abstract

Cardiovascular diseases are the leading cause of global mortality, accounting for roughly one-third of all deaths. Dyslipidemia is a key risk factor for atherosclerotic cardiovascular disease (ASCVD) and often coexists with diabetes, which exacerbates ASCVD risk. Despite the comprehensive management of dyslipidemia in patients with diabetes through pharmacological and non-pharmacological approaches, many individuals struggle to meet lipid targets through lifestyle changes alone. Therefore, pharmacological interventions are essential. Pharmacotherapy options for dyslipidemia in patients with diabetes, including those currently under development, have gained attention, particularly regarding their impact on cardiovascular outcomes. In this narrative review, we explore the data on cardiovascular outcomes related to established and emerging pharmacotherapy in the management of dyslipidemia in diabetes, such as statins, ezetimibe, bempedoic acid, PCSK9 inhibitors, icosapent ethyl, inclisiran, other lipid-lowering agents (fibrates, bile acid sequestrants, niacin), and novel medications such as antisense nucleotides and cholesterol ester transfer protein inhibitors. We aim to provide a summary that will help navigate the extensive evidence base on cardiovascular outcomes trials of these agents. We found that statins, particularly atorvastatin, showed the strongest and most consistent evidence on cardiovascular outcomes in patients with diabetes, with high-intensity statin therapy associated with significant reductions in major adverse cardiovascular events (MACE). Therefore, clinicians should prioritize statin therapy as the first-line pharmacotherapy for managing dyslipidemia in patients with diabetes to optimize cardiovascular outcomes. Studies also showed that the duration of statin therapy is the strongest predictor of MACE, followed by the achieved LDL cholesterol level and statin intensity. Additional lipid-lowering agents, such as ezetimibe or PCSK9 inhibitors, should be considered for patients who do not achieve target LDL cholesterol levels or for those who are statin-intolerant.