Retatrutide-Associated Improvements in Cardiovascular Risk Biomarkers in Adults With Obesity With or Without Type 2 Diabetes.

IF 6.1 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes, Obesity & Metabolism Pub Date : 2026-11-01 Epub Date: 2026-08-17 DOI:10.1111/dom.71200

Giacomo Ruotolo, Charles Harris, Yanzhu Lin, Jonathan M Wilson, Valentina Pirro, Kevin L Duffin, Melissa K Thomas, Mark L Hartman, Ciara O' Neill, Tamer Coskun, Zvonko Milicevic, Axel Haupt, Naveed Sattar, Stephen J Nicholls

{"title":"Retatrutide-Associated Improvements in Cardiovascular Risk Biomarkers in Adults With Obesity With or Without Type 2 Diabetes.","authors":"Giacomo Ruotolo, Charles Harris, Yanzhu Lin, Jonathan M Wilson, Valentina Pirro, Kevin L Duffin, Melissa K Thomas, Mark L Hartman, Ciara O' Neill, Tamer Coskun, Zvonko Milicevic, Axel Haupt, Naveed Sattar, Stephen J Nicholls","doi":"10.1111/dom.71200","DOIUrl":null,"url":null,"abstract":"Aims: To further characterise the effects of retatrutide on cardiometabolic risk, lipoprotein and inflammatory biomarkers were assessed post hoc in phase 2 trials of adults with obesity/overweight with or without type 2 diabetes (T2D).Materials and methods: Data were analysed from two randomised, double-blind, placebo-controlled phase 2 trials. In Study 1, adults with obesity/overweight and T2D received once-weekly retatrutide (0.5/4/8/12 mg), dulaglutide (1.5 mg) or placebo for 36 weeks; in Study 2, adults with clinical obesity without T2D received retatrutide (1/4/8/12 mg) or placebo for 48 weeks. Fasting blood samples were collected at baseline and during treatment to assess lipids, apolipoproteins, lipoprotein particle subclasses and inflammatory biomarkers. Mixed models for repeated measures estimated placebo-adjusted change from baseline. Statistical significance was defined as a false discovery rate-adjusted p < 0.05.Results: Mean body mass index was 35.4 kg/m2 (Study 1) and 37.4 kg/m2 (Study 2). In both studies, retatrutide was associated with significant reductions in non-high-density lipoprotein cholesterol (Study 1: up to -21.0%, Study 2: up to -26.9%), apolipoprotein B (-21.4%, -24.2%), total triglyceride-rich lipoprotein particles (-22.5%, -33.7%), large triglyceride-rich lipoprotein particles (-84.4%, -76.6%), triglyceride-rich lipoprotein cholesterol (-29.4%, -38.6%), total low-density lipoprotein particles (-19.7%, -23.5%) and small low-density lipoprotein particles (-32.6%, -32.3%). Retatrutide was associated with significant reductions in high-sensitivity C-reactive protein (-54.8%) and interleukin-6 (-29.6%) in Study 2 but not Study 1.Conclusions: In adults with obesity/overweight, with or without T2D, retatrutide treatment was associated with reductions in atherogenic lipoproteins and inflammatory biomarkers linked to cardiovascular disease risk.Trial registration: ClinicalTrials.gov numbers NCT04881760 and NCT04867785.","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":"10183-10194"},"PeriodicalIF":6.1000,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646367/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes, Obesity & Metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/dom.71200","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/8/17 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Aims: To further characterise the effects of retatrutide on cardiometabolic risk, lipoprotein and inflammatory biomarkers were assessed post hoc in phase 2 trials of adults with obesity/overweight with or without type 2 diabetes (T2D).

Materials and methods: Data were analysed from two randomised, double-blind, placebo-controlled phase 2 trials. In Study 1, adults with obesity/overweight and T2D received once-weekly retatrutide (0.5/4/8/12 mg), dulaglutide (1.5 mg) or placebo for 36 weeks; in Study 2, adults with clinical obesity without T2D received retatrutide (1/4/8/12 mg) or placebo for 48 weeks. Fasting blood samples were collected at baseline and during treatment to assess lipids, apolipoproteins, lipoprotein particle subclasses and inflammatory biomarkers. Mixed models for repeated measures estimated placebo-adjusted change from baseline. Statistical significance was defined as a false discovery rate-adjusted p < 0.05.

Results: Mean body mass index was 35.4 kg/m² (Study 1) and 37.4 kg/m² (Study 2). In both studies, retatrutide was associated with significant reductions in non-high-density lipoprotein cholesterol (Study 1: up to -21.0%, Study 2: up to -26.9%), apolipoprotein B (-21.4%, -24.2%), total triglyceride-rich lipoprotein particles (-22.5%, -33.7%), large triglyceride-rich lipoprotein particles (-84.4%, -76.6%), triglyceride-rich lipoprotein cholesterol (-29.4%, -38.6%), total low-density lipoprotein particles (-19.7%, -23.5%) and small low-density lipoprotein particles (-32.6%, -32.3%). Retatrutide was associated with significant reductions in high-sensitivity C-reactive protein (-54.8%) and interleukin-6 (-29.6%) in Study 2 but not Study 1.

Conclusions: In adults with obesity/overweight, with or without T2D, retatrutide treatment was associated with reductions in atherogenic lipoproteins and inflammatory biomarkers linked to cardiovascular disease risk.

Trial registration: ClinicalTrials.gov numbers NCT04881760 and NCT04867785.

查看原文本刊更多论文

利特鲁肽对伴有或不伴有2型糖尿病的成人肥胖患者心血管风险生物标志物的改善

目的：为了进一步表征利曲鲁肽对心脏代谢风险的影响，在伴有或不伴有2型糖尿病（T2D）的成人肥胖/超重患者的2期试验中，对脂蛋白和炎症生物标志物进行了事后评估。材料和方法：数据分析来自两个随机、双盲、安慰剂对照的2期试验。在研究1中，患有肥胖/超重和T2D的成年人接受每周一次的利特鲁肽（0.5/4/8/12 mg）、杜拉鲁肽（1.5 mg）或安慰剂治疗，持续36周；在研究2中，临床肥胖且无T2D的成年人接受利曲鲁肽（1/4/8/12 mg）或安慰剂治疗48周。在基线和治疗期间收集空腹血液样本，以评估血脂、载脂蛋白、脂蛋白颗粒亚类和炎症生物标志物。重复测量的混合模型估计安慰剂调整后的基线变化。结果：平均体重指数为35.4 kg/m2（研究1）和37.4 kg/m2（研究2）。在这两项研究中，利特鲁肽与非高密度脂蛋白胆固醇的显著降低相关(研究1：高达-21.0%，研究2：高达-26.9%)，载脂蛋白B(-21.4%, -24.2%)，总富甘油三酯脂蛋白颗粒（-22.5%,-33.7%），大富甘油三酯脂蛋白颗粒（-84.4%,-76.6%），富甘油三酯脂蛋白胆固醇（-29.4%,-38.6%），总低密度脂蛋白颗粒（-19.7%,-23.5%）和小低密度脂蛋白颗粒（-32.6%,-32.3%）。在研究2中，利特鲁肽与高敏c反应蛋白（-54.8%）和白细胞介素-6（-29.6%）的显著降低相关，但在研究1中没有。结论：在肥胖/超重的成年人中，伴有或不伴有T2D，利特鲁肽治疗与动脉粥样硬化脂蛋白和与心血管疾病风险相关的炎症生物标志物的降低相关。试验注册：ClinicalTrials.gov编号NCT04881760和NCT04867785。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Diabetes, Obesity & Metabolism 医学-内分泌学与代谢

CiteScore

10.90

自引率

6.90%

发文量

319

审稿时长

3-8 weeks

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.