Bertrand Cariou MD, An Thys PhD, Arsênio Rodrigues Oliveira PhD, Marine P. M. Letertre PhD, Béatrice Guyomarch MSc, Maxime Carpentier MD, Claire Cannet PhD, Pierre Morcel MD, Audrey Ernould PharmD, Laurent Flet MD, Patrick Giraudeau PhD, Samy Hadjadj MD, Cédric Le May PhD, Mikaël Croyal PhD
{"title":"alirocumab对2型糖尿病患者餐后高脂血症的影响：一项随机、双盲、安慰剂对照的交叉试验","authors":"Bertrand Cariou MD, An Thys PhD, Arsênio Rodrigues Oliveira PhD, Marine P. M. Letertre PhD, Béatrice Guyomarch MSc, Maxime Carpentier MD, Claire Cannet PhD, Pierre Morcel MD, Audrey Ernould PharmD, Laurent Flet MD, Patrick Giraudeau PhD, Samy Hadjadj MD, Cédric Le May PhD, Mikaël Croyal PhD","doi":"10.1111/dom.16305","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aims</h3>\n \n <p>Postprandial hyperlipidaemia (PPL), characterized by elevated triglyceride (TG) concentrations after a meal, is common in type 2 diabetes (T2D) and is often recognized as an independent cardiovascular risk factor. Here, we aimed to assess the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition by alirocumab on PPL in patients with T2D.</p>\n </section>\n \n <section>\n \n <h3> Materials and Methods</h3>\n \n <p>EUTERPE is a randomized, double-blind, placebo-controlled cross-over trial conducted in male patients with T2D. Participants received sequentially two sequences of 10-week treatment (alirocumab 75 mg Q2W or placebo s/c) with a wash-out period of 10 weeks. The primary end-point was the percentage reduction in plasma TG response after an oral fat load (incremental area under the curve [iAUC]<sub>0-8h</sub> TG). Secondary end-points included mass spectrometry-based apolipoprotein measurements and nuclear magnetic resonance (NMR)-based lipoprotein profiling.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Fourteen participants were included: age 59 ± 9 years, BMI 32.8 ± 5.5 kg/m<sup>2</sup>, HbA<sub>1C</sub> 6.7 ± 0.5%. Compared to placebo, alirocumab did not reduce PPL (iAUC<sub>0-8h</sub> TG: -5% [CI 95%: −28, +25], <i>p</i> = 0.68). Alirocumab decreased fasting non-HDL cholesterol (−38.5 ± 5.6%, <i>p</i> = 0.0003), remnant cholesterol (−20.0 ± 13.3%, <i>p</i> = 0.04), apoB100 (−21.2 ± 6.4%, <i>p</i> = 0.004) and apoE (−15.3 ± 6.6%, <i>p</i> = 0.02) concentrations. NMR analyses showed that alirocumab decreased both postprandial VLDL<sub>2</sub> cholesterol (−42% [−55, −25], <i>p</i> < 0.001) and IDL cholesterol (−26% [−38, −12], <i>p</i> = 0.0007), without effect on VLDL<sub>1</sub> cholesterol or TG concentrations.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Inhibition of PCSK9 by alirocumab did not reduce PPL in T2D, confirming that PCSK9 controls remnant cholesterol catabolism rather than intestinal chylomicron production.</p>\n </section>\n </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"27 6","pages":"3006-3016"},"PeriodicalIF":5.7000,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effect of alirocumab on postprandial hyperlipidaemia in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled, cross-over trial\",\"authors\":\"Bertrand Cariou MD, An Thys PhD, Arsênio Rodrigues Oliveira PhD, Marine P. M. Letertre PhD, Béatrice Guyomarch MSc, Maxime Carpentier MD, Claire Cannet PhD, Pierre Morcel MD, Audrey Ernould PharmD, Laurent Flet MD, Patrick Giraudeau PhD, Samy Hadjadj MD, Cédric Le May PhD, Mikaël Croyal PhD\",\"doi\":\"10.1111/dom.16305\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Aims</h3>\\n \\n <p>Postprandial hyperlipidaemia (PPL), characterized by elevated triglyceride (TG) concentrations after a meal, is common in type 2 diabetes (T2D) and is often recognized as an independent cardiovascular risk factor. Here, we aimed to assess the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition by alirocumab on PPL in patients with T2D.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Materials and Methods</h3>\\n \\n <p>EUTERPE is a randomized, double-blind, placebo-controlled cross-over trial conducted in male patients with T2D. Participants received sequentially two sequences of 10-week treatment (alirocumab 75 mg Q2W or placebo s/c) with a wash-out period of 10 weeks. The primary end-point was the percentage reduction in plasma TG response after an oral fat load (incremental area under the curve [iAUC]<sub>0-8h</sub> TG). Secondary end-points included mass spectrometry-based apolipoprotein measurements and nuclear magnetic resonance (NMR)-based lipoprotein profiling.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Fourteen participants were included: age 59 ± 9 years, BMI 32.8 ± 5.5 kg/m<sup>2</sup>, HbA<sub>1C</sub> 6.7 ± 0.5%. Compared to placebo, alirocumab did not reduce PPL (iAUC<sub>0-8h</sub> TG: -5% [CI 95%: −28, +25], <i>p</i> = 0.68). Alirocumab decreased fasting non-HDL cholesterol (−38.5 ± 5.6%, <i>p</i> = 0.0003), remnant cholesterol (−20.0 ± 13.3%, <i>p</i> = 0.04), apoB100 (−21.2 ± 6.4%, <i>p</i> = 0.004) and apoE (−15.3 ± 6.6%, <i>p</i> = 0.02) concentrations. NMR analyses showed that alirocumab decreased both postprandial VLDL<sub>2</sub> cholesterol (−42% [−55, −25], <i>p</i> < 0.001) and IDL cholesterol (−26% [−38, −12], <i>p</i> = 0.0007), without effect on VLDL<sub>1</sub> cholesterol or TG concentrations.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Inhibition of PCSK9 by alirocumab did not reduce PPL in T2D, confirming that PCSK9 controls remnant cholesterol catabolism rather than intestinal chylomicron production.</p>\\n </section>\\n </div>\",\"PeriodicalId\":158,\"journal\":{\"name\":\"Diabetes, Obesity & Metabolism\",\"volume\":\"27 6\",\"pages\":\"3006-3016\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2025-03-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes, Obesity & Metabolism\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.16305\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes, Obesity & Metabolism","FirstCategoryId":"3","ListUrlMain":"https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.16305","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Effect of alirocumab on postprandial hyperlipidaemia in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled, cross-over trial
Aims
Postprandial hyperlipidaemia (PPL), characterized by elevated triglyceride (TG) concentrations after a meal, is common in type 2 diabetes (T2D) and is often recognized as an independent cardiovascular risk factor. Here, we aimed to assess the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition by alirocumab on PPL in patients with T2D.
Materials and Methods
EUTERPE is a randomized, double-blind, placebo-controlled cross-over trial conducted in male patients with T2D. Participants received sequentially two sequences of 10-week treatment (alirocumab 75 mg Q2W or placebo s/c) with a wash-out period of 10 weeks. The primary end-point was the percentage reduction in plasma TG response after an oral fat load (incremental area under the curve [iAUC]0-8h TG). Secondary end-points included mass spectrometry-based apolipoprotein measurements and nuclear magnetic resonance (NMR)-based lipoprotein profiling.
Results
Fourteen participants were included: age 59 ± 9 years, BMI 32.8 ± 5.5 kg/m2, HbA1C 6.7 ± 0.5%. Compared to placebo, alirocumab did not reduce PPL (iAUC0-8h TG: -5% [CI 95%: −28, +25], p = 0.68). Alirocumab decreased fasting non-HDL cholesterol (−38.5 ± 5.6%, p = 0.0003), remnant cholesterol (−20.0 ± 13.3%, p = 0.04), apoB100 (−21.2 ± 6.4%, p = 0.004) and apoE (−15.3 ± 6.6%, p = 0.02) concentrations. NMR analyses showed that alirocumab decreased both postprandial VLDL2 cholesterol (−42% [−55, −25], p < 0.001) and IDL cholesterol (−26% [−38, −12], p = 0.0007), without effect on VLDL1 cholesterol or TG concentrations.
Conclusions
Inhibition of PCSK9 by alirocumab did not reduce PPL in T2D, confirming that PCSK9 controls remnant cholesterol catabolism rather than intestinal chylomicron production.
期刊介绍：
Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.
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