Inhibición de la proproteína convertasa subtilisina/kexina tipo 9 en el tratamiento de la hipercolesterolemia

Ascaso, Juan F.

doi:10.1016/j.endonu.2016.02.002

Cited by 4 publications

(2 citation statements)

References 14 publications

(12 reference statements)

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“…Inhibition of the PCSK9 enzyme prevents LDLR degradation after cellular internalization, reducing LDL-c by about 60%. Approved in 2015, monoclonal antibodies against PCSK9 (alirocumab and evolocumab) have shown a favourable safety profile with few side effects [ 108 ], but the consequences on glucose metabolism are still not clear. Despite the fact that most clinical studies have not found an association between PCSK9-i and NODM or worsening of pre-existing DM [ 87 , 109 ].…”

Section: Familial Hypercholesterolemia and Glucose Metabolism: Risk O...mentioning

confidence: 99%

Diabetes and Familial Hypercholesterolemia: Interplay between Lipid and Glucose Metabolism

et al. 2022

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Familial hypercholesterolemia (FH) is a genetic disease characterized by high low-density lipoprotein (LDL) cholesterol (LDL-c) concentrations that increase cardiovascular risk and cause premature death. The most frequent cause of the disease is a mutation in the LDL receptor (LDLR) gene. Diabetes is also associated with an increased risk of cardiovascular disease and mortality. People with FH seem to be protected from developing diabetes, whereas cholesterol-lowering treatments such as statins are associated with an increased risk of the disease. One of the hypotheses to explain this is based on the toxicity of LDL particles on insulin-secreting pancreatic β-cells, and their uptake by the latter, mediated by the LDLR. A healthy lifestyle and a relatively low body mass index in people with FH have also been proposed as explanations. Its association with superimposed diabetes modifies the phenotype of FH, both regarding the lipid profile and cardiovascular risk. However, findings regarding the association and interplay between these two diseases are conflicting. The present review summarizes the existing evidence and discusses knowledge gaps on the matter.

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Section: Familial Hypercholesterolemia and Glucose Metabolism: Risk O...mentioning

confidence: 99%

Diabetes and Familial Hypercholesterolemia: Interplay between Lipid and Glucose Metabolism

et al. 2022

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“…The interest in proprotein convertase subtilisin/kexin type 9 (PCSK9) as a lipid-lowering target arose at the beginning of the present century after the identification of several families with familial hypercholesterolemia (FH) who carried gain-of-function mutations in the gene encoding PCSK9. The subsequent observation that loss-of-function gene variants were associated with reduced low-density lipoprotein (LDL) cholesterol (C) levels and fewer cardiovascular events led to its consideration as a potential drug target [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of PCSK9 inhibitors in glycaemic control and new-onset diabetes

González-Lleó,

Sánchez-Hernández,

Plana

et al. 2024

Cardiovasc Diabetol

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Background The diabetogenic effect of statins has been well established by clinical trials, Mendelian randomisation studies and meta-analyses. According to large clinical trials, PCSK9 inhibitors (PCSK9i) have no deleterious impact on glucose metabolism. However, few real-life studies have yet evaluated the long-term effects of these drugs on glucose homeostasis and their impact on new-onset diabetes (NODM). Methods We studied 218 patients treated with either alirocumab or evolocumab (70% with familial hypercholesterolemia) for at least three years (PCSK9iG). We studied the NODM rate in the nondiabetic group at baseline (168) and overall glucose metabolism control in the whole group. Incidental DM was compared with two groups. The first was a propensity score matching (PSM)-selected group (n = 168) from the database of patients attending the Reus lipid unit (Metbank, n = 745) who were not on PCSK9i (PSMG). The second was a subgroup with a similar age range (n = 563) of the Di@bet.es study (Spanish prospective study on diabetes development n = 5072) (D@G). The incidence was reported as the percentage of NODM cases per year. Results The fasting glucose (FG) level of the subjects with normoglycaemia at baseline increased from 91 (86-95.5) to 93 (87–101) mg/dL (p = 0.014). There were 14 NODM cases in the PCSK9i group (2.6%/y), all among people with prediabetes at baseline. The incidence of NODM in PSMG and D@G was 1.8%/y (p = 0.69 compared with the PCSK9iG). The incidence among the subjects with prediabetes was 5.1%/y in the PCSK9iG, 4.8%/y in the PSMG and 3.9%/y in the D@G (p = 0.922 and p = 0.682, respectively). In the multivariate analysis, only the FG level was associated with the development of NODM in the PCSK9iG (OR 1.1; 95% CI: 1.0-1.3; p = 0.027). Neither FG nor A1c levels changed significantly in patients with DM at baseline. Conclusion A nonsignificant increase in NODM occurred in the PCSK9iG, particularly in patients with prediabetes, compared with the PSMG and D@G groups. Baseline FG levels were the main variable associated with the development of DM. In the subjects who had DM at baseline, glucose control did not change. The impact of PCSK9i on glucose metabolism should not be of concern when prescribing these therapies.

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Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. A new drug class for the treatment of hypercholesterolemia

Victoria

2017

Endocrinología, Diabetes y Nutrición (English ed.)

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Inhibición de la proproteína convertasa subtilisina/kexina tipo 9 en el tratamiento de la hipercolesterolemia

Cited by 4 publications

References 14 publications

Diabetes and Familial Hypercholesterolemia: Interplay between Lipid and Glucose Metabolism

Diabetes and Familial Hypercholesterolemia: Interplay between Lipid and Glucose Metabolism

Impact of PCSK9 inhibitors in glycaemic control and new-onset diabetes

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. A new drug class for the treatment of hypercholesterolemia

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