Managing dyslipidemia in patients with Type 2 diabetes

ABSTRACT

Introduction

Type 2 diabetes mellitus (T2DM) is associated with increased risk for atherosclerotic cardiovascular disease (ASCVD) which is partly related to atherogenic dyslipidemia with raised triglycerides, reduced high-density lipoprotein cholesterol levels, and accompanying lipid changes. Treatment of this dyslipidemia is regarded as a priority to reduce the ASCVD risk in T2DM.

Areas covered

This article reviews the relevant studies and guidelines from the publications related to this area.

Expert opinion

Lifestyle modification should always be encouraged, and statin treatment is indicated in most patients with T2DM based on the outcome of randomized controlled trials. If LDL-C goals are not achieved, first, ezetimibe and subsequently proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors should be added. Patients with T2DM derive greater benefits from ezetimibe and PCSK9 inhibitors due to their higher absolute ASCVD risk compared to patients without T2DM. If triglyceride levels remain elevated, a high dose of eicosapentaenoic acid ethyl ester should be added. Fibrates should be used for severe hypertriglyceridemia to prevent acute pancreatitis. Novel treatments including pemafibrate and inclisiran are undergoing cardiovascular outcome trials, and RNA-based therapies may help to target residual hypertriglyceridemia and high lipoprotein(a) with the long acting treatments offering potential improved adherence to therapy.

KEYWORDS:

• Diabetes
• dyslipidemia
• ezetimibe
• fibrates
• icosapent ethyl
• proprotein convertase subtilisin-kexin type 9 inhibitors
• statins

Article highlights

• Most patients with T2DM are considered to be in the higher risk categories for ASCVD and lifestyle interventions and pharmacotherapy for dyslipidemia are indicated.

• Statin treatment is recommended for primary and secondary prevention for almost all patients with T2DM with a treatment intensity or LDL-C target depending on the level of ASCVD risk.

• Ezetimibe and the PCSK9 mAbs should be added to maximally tolerated statin therapy to achieve the relevant targets for LDL-C and non-HDL-C.

• EPA as icosapent ethyl is recommended for patients with persisting elevation of triglycerides after achieving LDL-C targets and fibrates should be used in patients with severe elevation of triglycerides to prevent acute pancreatitis.

• Pemafibrate and inclisiran may prove to have an important role in some patients with T2DM and the RNA-based therapeutics in development targeting apoCIII, ANGPTL3, and Lp(a) may prove to have important indications in certain very high-risk patients with T2DM.

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Declaration of interest

B. Tomlinson has acted as consultant or speaker for Amgen Inc, Kowa, and Merck Serono for which he received honoraria. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One reviewer has served as a consultant and/or speaker for Boehringer Ingelheim, Novartis, Shire, Biofarm, Eli Lilly and Company, and Krka. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was funded by faculty research funding from the Faculty of Medicine, Macau University of Science and Technology.