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July 29, 2026

Lipid management in type 2 diabetes and non-HDL-cholesterol

target all atherogenic lipoproteins.

Julia Brandts, Marlo Verket, Alberto Zambon et al. - Cardiovascular diabetology

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality in diabetes, partly driven by dyslipidaemia. Although LDL cholesterol (LDL-C) is the primary treatment target, many patients with diabetes have mixed dyslipidaemia with elevated triglycerides and atherogenic remnant lipoproteins, better captured by non-HDL cholesterol (non-HDL-C). Guidelines from the ADA, AACE and ESC recommend both LDL-C and non-HDL-C targets based on individual risk, yet target attainment remains suboptimal in practice. Statins, ezetimibe, bempedoic acid and PCSK9 inhibitors effectively lower LDL-C and non-HDL-C and reduce cardiovascular risk; triglyceride-lowering agents (omega-3, fibrates) lower triglycerides but their effect on hard outcomes remains uncertain. This review argues for using non-HDL-C and apolipoprotein B (apoB) alongside LDL-C as measures of atherogenic burden, and for more targeted treatment of residual atherogenic particles in diabetes.

Summary

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality in individuals with diabetes, partly driven by dyslipidemia. While low-density lipoprotein cholesterol (LDL-C) reduction is the primary target of lipid management, many patients with diabetes exhibit mixed dyslipidemia characterised by elevated triglycerides and increased concentrations of atherogenic remnant lipoproteins, which are more comprehensively captured by non-high-density lipoprotein cholesterol (non-HDL-C). Current guidelines from international societies, including the American Diabetes Association (ADA), the American Association of Clinical Endocrinology (AACE), and the European Society of Cardiology (ESC), recommend LDL-C and non-HDL-C targets based on individual cardiovascular risk profiles. Despite clear therapeutic algorithms, lipid target attainment remains suboptimal in routine clinical practice, necessitating more intensive and individualised treatment strategies. Lipid-lowering therapies, including statins, ezetimibe, bempedoic acid and PCSK9 inhibitors, effectively reduce LDL-C and non-HDL-C, significantly lowering cardiovascular risk. Triglyceride-lowering therapies, including omega-3 fatty acids and fibrates, have demonstrated substantial reductions in triglyceride levels, but their impact on cardiovascular outcomes remains uncertain. Given the heterogeneity of dyslipidemia in diabetes, non-HDL-C and apolipoprotein B (apoB) have emerged as superior markers for assessing atherogenic burden. While LDL-C reduction remains central, additional efforts are needed to optimise the management of residual atherogenic lipoprotein particles in diabetes. Future research should focus on refining risk stratification, improving lipid target attainment, and integrating novel lipid-modifying agents to enhance cardiovascular outcomes in this high-risk population.