Lipid management in type 2 diabetes and non-HDL-cholesterol: target all atherogenic lipoproteins

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.

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Publication Details

Journal
Cardiovascular Diabetology
Published
2026-04-12
DOI
https://doi.org/10.1186/s12933-026-03166-4
Primary Topic
Lipoproteins and Cardiovascular Health
Type
article
Field-Weighted Citation Impact
0.00

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article

Lipid management in type 2 diabetes and non-HDL-cholesterol: target all atherogenic lipoproteins

Marlo Verket, Massimo Federici, D. Müller-Wieland, Julia Brandts et al.
Cardiovascular Diabetology
Lipoproteins and Cardiovascular Health
article

Lipid management in type 2 diabetes and non-HDL-cholesterol: target all atherogenic lipoproteins

Marlo Verket, Massimo Federici, D. Müller-Wieland, Julia Brandts, Alberto Zambon, Nikolaus Marx
article en

Abstract

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.

Cardiovascular DiabetologyVol. 25(1)
University of Rome Tor Vergata (IT), University of Padua (IT), Istituto Neurologico Mediterraneo (IT), Imperial College London (GB), RWTH Aachen University (DE)
Amgen, Eli Lilly and Company, AstraZeneca, Sanofi, Amarin Corporation, Mylan, Deutsche Forschungsgemeinschaft, Daiichi-Sankyo, Novo Nordisk, RWTH Aachen University, Daiichi Sankyo Europe
Good health and well-being
Openalex Percentile: Top 29%
Lipoproteins and Cardiovascular Health
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