摘要：《柳叶刀》最新发表一项关于SELECT试验的最新分析，该研究是迄今最大规模、最长时间的评估司美格鲁肽（一种用于支持减重和糖尿病管理的药物）心血管益处的临床试验。研究证实，即使没有糖尿病，超重或肥胖且已有心脏病的人群服用司美格鲁肽，也能降低重大心脏事件的风险。更

《柳叶刀》最新发表一项关于SELECT试验的最新分析，该研究是迄今最大规模、最长时间的评估司美格鲁肽（一种用于支持减重和糖尿病管理的药物）心血管益处的临床试验。研究证实，即使没有糖尿病，超重或肥胖且已有心脏病的人群服用司美格鲁肽，也能降低重大心脏事件的风险。更重要的是，这种心脏保护作用与体重减轻的程度或基础体重无关。

SELECT试验最初研究了超过17,000名患有心脏病且BMI≥27的成人，比较司美格鲁肽与安慰剂的效果。此次最新分析重点关注患者在试验期间体重和腰围的变化，以及这些变化与心脏病发作和中风等心血管事件的关系。研究发现，虽然司美格鲁肽帮助人们减轻体重和缩小腰围，但早期的体重减轻并不能预测心脏问题的发生率。然而，腰围缩小（即腹部脂肪减少）与更好的心脏结局相关，并且约解释司美格鲁肽整体益处的三分之一。

作者指出，这些发现表明，司美格鲁肽除了减重外，还能带来重要的心血管保护作用，为治疗和预防肥胖及心血管疾病提供了新的思路。

司美格鲁肽与基础及变化的脂肪指标对心血管结局的影响：SELECT试验的预设分析

背景

SELECT试验发现，司美格鲁肽能降低超重或肥胖伴心血管疾病但未患糖尿病患者的主要不良心血管事件（MACE）风险。本文为该试验的预设分析，探讨基础脂肪指标、治疗引起的脂肪变化与后续MACE风险之间的关系。

方法

研究对象为45岁及以上、BMI≥27kg/m²的患者，来自41个国家（804个站点），随机1:1分配接受每周一次的2.4毫克司美格鲁肽或安慰剂。主要结局为首次发生的MACE（心血管死亡、非致死性心肌梗死或非致死性中风）。脂肪指标包括体重和腰围。在本分析中，评估20周后MACE风险与前20周脂肪变化的关系；在另一分析中，评估104周内所有MACE事件与脂肪变化的关系。该试验已在ClinicalTrials.gov注册（NCT03574597）。

结果

在SELECT试验中17,404名患者中，司美格鲁肽显著降低了MACE发生率，且在所有基础体重和腰围类别中均表现出一致的益处。在司美格鲁肽组，线性趋势分析显示，基础体重越低、腰围越小，MACE风险越低：每减少5公斤体重，风险降低约4%（HR 0.96，95% CI 0.94–0.99；p=0.001），每减少5厘米腰围，风险也降低约4%（HR 0.96，95% CI 0.93–0.99；p=0.004）。在安慰剂组，基础腰围较小（HR 0.96，95% CI 0.94–0.99；p=0.007）与较低的MACE风险相关，而基础体重与风险无显著关系（HR 0.99，95% CI 0.97–1.01；p=0.28），且体重减轻反而与MACE风险增加有关。在接受司美格鲁肽的患者中，20周时的体重减轻与后续MACE风险没有线性关系，但20周时腰围的缩小越多与更低的后续MACE风险相关，104周时腰围的缩小也与试验期内的MACE风险降低有关。经调整腰围随时间变化的影响后，估算约33%的MACE益处通过腰围缩小来介导实现（HR 0.86，95% CI 0.77–0.97）。

图2：累计发生率图，显示从随机分配到首次重大不良心血管事件（MACE）的时间，

按第20周体重减轻情况划分（A）安慰剂组和（B）司美鲁肽组。

图3：累计发生率图，显示从随机分配到首次重大不良心血管事件（MACE）的时间，

按第20周腰围变化情况划分（A）安慰剂组和（B）司美鲁肽组。

解释

司美格鲁肽的心血管保护作用与基础脂肪指标和体重减轻无关，且与腰围变化关系较小，提示其益处可能通过脂肪减少之外的机制实现。 END

Funding

Novo Nordisk.

Declaration of interests

JD declares having received consulting honoraria from Aegerion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and Takeda; and research grants from Aegerion, Alzheimer's Research UK, British Heart Foundation, Colgate, Medical Research Council (UK), MSD, National Institute for Health and Care Research, Pfizer, Public Health England, and Roche. AML declares having received consulting honoraria from Akebia, Alnylam, Amgen, Ardelyx, Becton Dickson, Brainstorm Cell, Eli Lilly, Endologix, Fibrogen, GlaxoSmithKline, Intarcia, Medtronic, Neovasc, Novo Nordisk, Provention Bio, and ReCor; and research funding to his institution from AbbVie, AstraZeneca, CSL Behring, Eli Lilly, Esperion, and Novartis. SEK declares having received consulting honoraria from Anji Pharmaceuticals, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, and Oramed; and holds stock options from Altpep. SSE declares having received consulting honoraria from 89 Bio, Amylyx, Avillion, Ayala, Bayer, BeiGene, Boehringer Ingelheim, BridgeBio, GlaxoSmithKline, Inovio, Insmed, Ipsen, Karuna, Lilly, Lundbeck, Mirati, Moderna, Novartis, Novavax, Novo Nordisk, NSABP, Pfizer, Principia, Reata, Rebiotx, Roche, Sanofi, SOLVD, Sutro Biopharma, and TG Therapeutics; and participation on a data monitoring or advisory board for 89 Bio, AstraZeneca, Bayer, BioAtla, Bristol Myers Squibb, Daiichi Sankyo, Denovo, Fore Therapeutics, and Immunome. IL declares having received research funding to their institution from Boehringer Ingelheim, Mylan, Novo Nordisk, and Sanofi; and advisory or consulting fees or other support from Altimmune, AstraZeneca, Bayer, Biomea, Boehringer Ingelheim, Carmot, Cytoki Pharma, Eli Lilly, Intercept, Janssen and J&J, MannKind, Mediflix, Merck, Metsera, Novo Nordisk, Pfizer, PharmaVentures, Regeneron, Sanofi, Shionogi, Structure Therapeutics, Target RWE, Terns Pharma, The Comm Group, Valeritas, WebMD, and Zealand Pharma. BMS declares having received institutional research grants to Brigham and Women's Hospital from Amgen, Better Therapeutics, Merck, Milestone Therapeutics, Novo Nordisk, and Pfizer; consulting fees from AbbVie, AstraZeneca, Boehringer Ingelheim, Better Therapeutics, Elsevier PracticeUpdate Cardiology, Esperion, Hanmi, Lexicon, and Novo Nordisk; and equity in health at Scale, Arboretum LifeSciences, and AIwithCare. JP declares having received consulting honoraria from Altimmune, Amgen, Boehringer Ingelheim, Corcept, Esperion Therapeutics, Merck, New Amsterdam, and Novo Nordisk; speakers' honoraria from Amgen, Boehringer Ingelheim, Corcept, Esperion Therapeutics, Merck, New Amsterdam, and Novo Nordisk; meeting and travel support from Amgen, Boehringer Ingelheim, Corcept, Esperion Therapeutics, Merck, New Amsterdam, and Novo Nordisk; grants from Boehringer Ingelheim and Novartis; and leadership or fiduciary roles in World Congress Insulin Resistance and Diabetes, Sarnoff Foundation, and cardiometabolic Alliance. RFK declares having received consulting honoraria from Altimmune, Antag, AstraZeneca, Boehringer Ingelheim, Currax, Eli Lilly, Novo Nordisk, Regeneron, Structure, and Weight Watchers. HMC declares serving on advisory panels for Bayer and Novo Nordisk; receiving research grants from Chief Scientist Office, Diabetes UK, European Commission, IQVIA, Juvenile Diabetes Research Foundation, and Medical Research Council; and holding stock options in Roche Pharmaceuticals. GKH, SS, PEW, OKJ, and RB are employees and stockholders of Novo Nordisk. C-CW declares institutional research grants from Amgen, Daiichi Sankyo, Gi Tai, MAC, MSD, Novo Nordisk, and Sanofi; speakers' honoraria from AstraZeneca, Chen-Hua, Daiichi Sankyo, Gi Tai, MAC, MSD, Novartis, Novo Nordisk, Pfizer, Sanofi, and Tanabe; and consulting honoraria from Daiichi Sankyo, MAC, Power-Biotech, Sanofi, and Tanabe. IK declares research grants from Daiichi Sankyo, Kowa Pharmaceutical, and Tanabe Mitsubishi Pharma Corporation; speakers' honoraria from AstraZeneca, Bayer, Kowa Pharmaceutical, Nippon Boehringer Ingelheim, Novo Nordisk, Ono Pharmaceutical, and Tanabe Mitsubishi Pharma Corporation; and affiliation with endowed Chairs from BioStream, Idorsia Pharmaceuticals Japan, Nippon Boehringer Ingelheim, Novo Nordisk, Takara Bio, and Toa Eiyo. FS has worked as a consultant, participated in studies, or received travel funds from the following companies that are involved with obesity, lipodystrophy, and diabetes: Aegerion (Amryt), BioItalia, Boehringer Ingelheim, Bruno Pharma, Lilly, Novo Nordisk, and Pfizer. JH declares having received consulting honoraria from AstraZeneca, Eli Lilly, Novo Nordisk, and Vivus. MU-T declares having received consulting and research honoraria from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Frosst Laboratories, Johnson & Johnson, Menarini, Novartis, Novo Nordisk, Pfizer, Procaps, Sanofi-Aventis, Servier, and Tecnofarma. SB declares having received advisory or consulting honoraria from Boehringer Ingelheim, Dompè, Eli Lilly, Novo Nordisk, and Pfizer. DHR declares having received consulting honoraria from AbbVie, Altimmune, Amgen, AstraZeneca, Biohaven, Boehringer Ingelheim, Calibrate, Carmot Therapeutics (Roche), CinRx, Eli Lilly, eMedd, Epitomee, Gila Therapeutics, Ifa Celtic, Novo Nordisk, Pfizer, Regeneron, Rhythm, Scientific Intake, Source Bio, Structure Therapeutics, Tenvie, Wondr Health, and Zealand Pharma; and stock options from Calibrate, Epitomee, Scientific Intake, and Xeno Bioscience.

中文翻译仅供参考，所有内容以英文原文为准。

https://doi.org/10.1016/S0140-6736(25)01375-3

来源：柳叶刀TheLancet