Usefulness of alirocumab and evolocumab for the treatment of patients with diabetic dyslipidemia

Zhang, Jun; Tecson, Kristen M.; Rocha, Natália A.; McCullough, Peter A.

doi:10.1080/08998280.2018.1441255

Cited by 10 publications

(10 citation statements)

References 25 publications

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“…It has been proposed that TH, by stimulating LDLR activity and clearance of LDL-C via PCSK9, may support this mechanism ( 13 ). Also of interest is the fact that the correlation of circulating PCSK9 levels with thyroid function, even in the normal range, may be blunted by obesity ( 96 ).…”

Section: Co-treatment With Statins Ezetimibe and Proprotein Convertmentioning

confidence: 99%

A Renewed Focus on the Association Between Thyroid Hormones and Lipid Metabolism

2018

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Thyroid dysfunction, manifesting as either overt or subclinical hypothyroidism, negatively affects lipid metabolism: this leads to hypercholesterolemia which progressively increases the risk for cardiovascular disease and, potentially, mortality. Hypercholesterolemia in hypothyroidism is mainly due to a reduction in low-density lipoprotein (LDL) receptor activity, this accompanied by concomitant diminishing control by triiodothyronine (T3) of sterol regulatory element-binding protein 2 (SREBP-2), which modulates cholesterol biosynthesis by regulating rate-limit degrading enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) activity. Recently, 3,5-diiodothyronine (T2), a natural thyroid hormone derivative, was found to repress the transcription factor carbohydrate-response element-binding protein (ChREBP) and also to be involved in lipid catabolism and lipogenesis, though via a different pathway than that of T3. While thyroid hormone could therapeutically reverse the dyslipidemic profile commonly occurring in hypothyroidism, it should be borne in mind that the potency of the effects may be age-and sex-dependent. Thyroid hormone administration possibly also sustains and enhances the efficacy of hypolipidemic drugs, such as statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9), in patients with dyslipidemia and hypothyroidism.

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Section: Co-treatment With Statins Ezetimibe and Proprotein Convertmentioning

confidence: 99%

A Renewed Focus on the Association Between Thyroid Hormones and Lipid Metabolism

2018

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“…These agents inhibit the binding of PCSK9 to LDL receptors, which targets them for lysosomal degradation. The currently available PCSK9 inhibitors, alirocumab and evolocumab, reduce LDL cholesterol to a greater degree than statins, typically by 50–60%, while also modestly elevating HDL by 7–11% [ 130 ]. These effects appear to be similar in patients with or without T2DM [ 131 ].…”

Section: Hdl-modifying Treatment Approaches In Diabetesmentioning

confidence: 99%

The Role of High-Density Lipoproteins in Diabetes and Its Vascular Complications

Wong

Nicholls

Tan

et al. 2018

IJMS

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Almost 600 million people are predicted to have diabetes mellitus (DM) by 2035. Diabetic patients suffer from increased rates of microvascular and macrovascular complications, associated with dyslipidaemia, impaired angiogenic responses to ischaemia, accelerated atherosclerosis, and inflammation. Despite recent treatment advances, many diabetic patients remain refractory to current approaches, highlighting the need for alternative agents. There is emerging evidence that high-density lipoproteins (HDL) are able to rescue diabetes-related vascular complications through diverse mechanisms. Such protective functions of HDL, however, can be rendered dysfunctional within the pathological milieu of DM, triggering the development of vascular complications. HDL-modifying therapies remain controversial as many have had limited benefits on cardiovascular risk, although more recent trials are showing promise. This review will discuss the latest data from epidemiological, clinical, and pre-clinical studies demonstrating various roles for HDL in diabetes and its vascular complications that have the potential to facilitate its successful translation.

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“…PCSK9 is a crucial protein for cholesterol homeostasis. The wild-type PCSK9 gene located on chromosome 1 was first described in 2003 and is primarily expressed in the liver 19,20. Within the liver, PCSK9 binds to the first EGF-like repeat A located on the LDL-Rs and shuttles the LDL-Rs intracellularly into the lysosomes for degradation.…”

Section: Pharmacological Approaches For the Management Of Diabetic Dymentioning

confidence: 99%

“…This action results in decreased degradation of the LDL-Rs, enabling more LDL-Rs to recycle back to the hepatocyte membrane to increase the plasma LDL-C clearance (Figure 1). 20…”

Section: Pharmacological Approaches For the Management Of Diabetic Dymentioning

confidence: 99%

<p>A spotlight on alirocumab in high cardiovascular risk patients with type 2 diabetes and mixed dyslipidemia: a review on the emerging data</p>

Rana¹,

Reid²,

Rosenwasser³

et al. 2019

DMSO

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Diabetes is a significant and independent risk factor for atherosclerotic cardiovascular disease (ASCVD), leading to morbidity and mortality among this population. The prevention of macrovascular complications, such as CVD, peripheral arterial disease, and cerebrovascular accident, in patients with diabetes is obtained through multifactorial risk reduction, including mixed dyslipidemia management and adequate glycemic control. For patients with diabetes, it is crucial to initiate adequate dyslipidemia therapy to achieve recommended low-density lipoprotein cholesterol (LDL-C) goal of <70 mg/dL or target non-high-density lipoprotein goal of <100 mg/dL. Lipid-lowering therapies (LLTs), such as statins and ezetimibe, are the cornerstone for plasma LDL-C lowering; however, individuals with diabetes are often unable to achieve target lipid goals with these therapies alone and frequently require additional treatments. A new class of LLTs, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, provides a novel approach to lowering lipids in persons with high CV risk, such as those with diabetes. The clinical data presented in this review indicate the potential benefits of alirocumab in patients with diabetes and its value as a treatment option in patients with diabetic dyslipidemia with no significant safety concerns.

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Usefulness of alirocumab and evolocumab for the treatment of patients with diabetic dyslipidemia

Cited by 10 publications

References 25 publications

A Renewed Focus on the Association Between Thyroid Hormones and Lipid Metabolism

A Renewed Focus on the Association Between Thyroid Hormones and Lipid Metabolism

The Role of High-Density Lipoproteins in Diabetes and Its Vascular Complications

<p>A spotlight on alirocumab in high cardiovascular risk patients with type 2 diabetes and mixed dyslipidemia: a review on the emerging data</p>

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