292-OR: Oral Semaglutide and Cardiovascular Outcomes by Baseline A1C and BMI in People with Type 2 Diabetes in the SOUL Trial

IF 7.5 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes Pub Date : 2025-06-23 DOI:10.2337/db25-292-or

SILVIO E. INZUCCHI, ROHANA ABDUL GHANI, JOHN DEANFIELD, MADS D.M. ENGELMANN, G. KEES HOVINGH, OLE K. JEPPESEN, MONIKA KELLERER, KABIRDEV MANDAVYA, JOHANNES F. MANN, NIKOLAUS MARX, CHANTAL MATHIEU, DARREN K. MCGUIRE, VISWANATHAN MOHAN, SHARON L. MULVAGH, RODICA POP-BUSUI, NEIL R. POULTER, MARIA SEJERSTEN RIPA, GABRIELA ROMAN, RÓBINSON SÁNCHEZ GARCÍA, MICHAEL SHECHTER, JOHN B. BUSE

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Methods: SOUL’s primary outcome was time to first MACE, assessed for this post hoc analysis by baseline A1c, BMI and body weight using Cox regression. Results: People with T2D (n=9650; A1c 6.5–10%) and known atherosclerotic CV disease (ASCVD) or chronic kidney disease (CKD) were randomized to oral sema or placebo and followed for a mean of 47.5 months. We found significant differences in MACE outcomes associated with oral sema use by baseline A1c, with greater effects apparent with A1c &gt;8.0% (Fig.). When the data were further analyzed across four A1c strata, the MACE benefit from oral sema appeared to apply to those with A1c &gt;7%. The effects of oral sema on MACE were the same in those with BMI above / below 30 kg/m2, as well as across all four BMI strata, and above / below the mean body weight (87.9 kg) (Fig.). Conclusion: In SOUL, the CV benefits of oral sema appeared more pronounced with higher A1c levels at baseline but were consistent across various BMI categories. These data may help inform the individualized use of oral sema in people with T2D and ASCVD and/or CKD. Disclosure S.E. Inzucchi: Consultant; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Merck & Co., Inc, Pfizer Inc, Bayer Pharmaceuticals, Inc. R. Abdul Ghani: None. J. Deanfield: Other Relationship; Aegerion Pharmaceuticals, Amgen Inc, AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Merck & Co., Inc, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Novo Nordisk A/S, Pfizer Inc. M.D.M. Engelmann: Employee; Novo Nordisk. G. Hovingh: Employee; Novo Nordisk. Stock/Shareholder; Novo Nordisk. O.K. Jeppesen: None. M. Kellerer: Advisory Panel; Abbott, Bayer Pharmaceuticals, Inc. Speaker's Bureau; Boehringer-Ingelheim, Johnson & Johnson Medical Devices Companies. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Sanofi. K. Mandavya: Employee; Novo Nordisk. J.F. 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引用次数: 0

Abstract

Introduction and Objective: In SOUL (NCT03914326), oral semaglutide (sema) 14 mg QD, a GLP-1 receptor agonist, reduced major adverse cardiovascular (CV) event (MACE) risk by 14%. GLP-1RAs are routinely prescribed to reduce A1c and BMI in type 2 diabetes (T2D). Whether the CV benefits of oral sema are influenced by baseline A1c or BMI is not fully known. Methods: SOUL’s primary outcome was time to first MACE, assessed for this post hoc analysis by baseline A1c, BMI and body weight using Cox regression. Results: People with T2D (n=9650; A1c 6.5–10%) and known atherosclerotic CV disease (ASCVD) or chronic kidney disease (CKD) were randomized to oral sema or placebo and followed for a mean of 47.5 months. We found significant differences in MACE outcomes associated with oral sema use by baseline A1c, with greater effects apparent with A1c >8.0% (Fig.). When the data were further analyzed across four A1c strata, the MACE benefit from oral sema appeared to apply to those with A1c >7%. The effects of oral sema on MACE were the same in those with BMI above / below 30 kg/m2, as well as across all four BMI strata, and above / below the mean body weight (87.9 kg) (Fig.). Conclusion: In SOUL, the CV benefits of oral sema appeared more pronounced with higher A1c levels at baseline but were consistent across various BMI categories. These data may help inform the individualized use of oral sema in people with T2D and ASCVD and/or CKD. Disclosure S.E. Inzucchi: Consultant; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Merck & Co., Inc, Pfizer Inc, Bayer Pharmaceuticals, Inc. R. Abdul Ghani: None. J. Deanfield: Other Relationship; Aegerion Pharmaceuticals, Amgen Inc, AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Merck & Co., Inc, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Novo Nordisk A/S, Pfizer Inc. M.D.M. Engelmann: Employee; Novo Nordisk. G. Hovingh: Employee; Novo Nordisk. Stock/Shareholder; Novo Nordisk. O.K. Jeppesen: None. M. Kellerer: Advisory Panel; Abbott, Bayer Pharmaceuticals, Inc. Speaker's Bureau; Boehringer-Ingelheim, Johnson & Johnson Medical Devices Companies. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Sanofi. K. Mandavya: Employee; Novo Nordisk. J.F. Mann: Other Relationship; AstraZeneca, Bayer Pharmaceuticals, Inc. Advisory Panel; Novo Nordisk. Board Member; AstraZeneca, Bayer Pharmaceuticals, Inc, Boehringer-Ingelheim, Novo Nordisk. Other Relationship; Sanofi. Consultant; AstraZeneca, Bayer Pharmaceuticals, Inc, Novo Nordisk. Research Support; AstraZeneca. Other Relationship; Boehringer-Ingelheim. Research Support; Novo Nordisk, Sanofi. Speaker's Bureau; AstraZeneca, Bayer Pharmaceuticals, Inc, Novo Nordisk, Novartis AG. Other Relationship; UpToDate Inc / KDIGO. N. Marx: Speaker's Bureau; Abbott, Amgen Inc, AstraZeneca. Advisory Panel; AstraZeneca. Speaker's Bureau; Bayer Pharmaceuticals, Inc. Advisory Panel; Bayer Pharmaceuticals, Inc. Speaker's Bureau; Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Daiichi Sankyo. Advisory Panel; Merck Sharp & Dohme Corp. Speaker's Bureau; Novo Nordisk. Advisory Panel; Novo Nordisk. Speaker's Bureau; Sanofi. Advisory Panel; Sanofi. Speaker's Bureau; Lilly Diabetes. C. Mathieu: Advisory Panel; Novo Nordisk, Sanofi, Eli Lilly and Company, Abbott, Medtronic, SAB Biotherapeutics, Inc, Roche Diabetes Care, Vertex Pharmaceuticals Incorporated, Biomea Fusion, Bayer Pharmaceuticals, Inc. D.K. McGuire: Consultant; Novo Nordisk. Advisory Panel; Novo Nordisk. Consultant; Lilly USA LLC. Advisory Panel; Lilly USA LLC. Consultant; Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim, AstraZeneca, ESPERION Therapeutics, Inc., NewAmsterdam Pharma, Pfizer Inc. Consultant; Applied Therapeutics, Lexicon Pharmaceuticals, Inc, Bayer Pharmaceuticals, Inc, Amgen Inc, Kailera, Idorsia, Alveus, Metsera. V. Mohan: Speaker's Bureau; Novo Nordisk. Advisory Panel; Abbott. Research Support; Servier Laboratories. Speaker's Bureau; USV Private Limited, Sanofi, Medtronic, Eli Lilly and Company. S.L. Mulvagh: Advisory Panel; Novo Nordisk, Merck & Co., Inc. R. Pop-Busui: Board Member; American Diabetes Association. Consultant; Averitas Pharma, Inc. Research Support; Bayer Pharmaceuticals, Inc. Other Relationship; Biogen. Research Support; Juvenile Diabetes Research Foundation (JDRF). Advisory Panel; Lexicon Pharmaceuticals, Inc, Novo Nordisk. Research Support; Novo Nordisk, National Institute of Diabetes and Digestive and Kidney Diseases. Consultant; Roche Diagnostics. N.R. Poulter: Consultant; Servier Laboratories, Alnylam Pharmaceuticals, Inc. Research Support; Servier Laboratories. Speaker's Bureau; AstraZeneca. Consultant; Aktiia. M. Ripa: Employee; Novo Nordisk. G. Roman: Advisory Panel; AstraZeneca. Consultant; Berlin-Chemie AG. Research Support; AstraZeneca. Advisory Panel; Boehringer-Ingelheim, Medtronic, Lilly Diabetes, Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Roche Diabetes Care, Sanofi, Viatris Inc. R. Sánchez García: None. M. Shechter: None. J.B. Buse: Other Relationship; Corcept Therapeutics, Dexcom, Inc., Novo Nordisk. Consultant; Altimmune Inc, Amgen Inc, ApStem, Aqua Medical, AstraZeneca, Boehringer-Ingelheim, CeQur, Eli Lilly and Company, embecta, GentiBio. Other Relationship; Glyscend Therapeutics. Consultant; Insulet Corporation, Medtronic. Other Relationship; Mellitus Health. Consultant; Metsera. Other Relationship; Pendulum Therapeutics, Praetego, Stability Health. Consultant; Tandem Diabetes Care, Inc, TERNS Pharmaceuticals, Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S. Funding Novo Nordisk A/S

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292-OR: SOUL试验中口服西马鲁肽与2型糖尿病患者基线A1C和BMI的心血管结局

在SOUL （NCT03914326）中，口服GLP-1受体激动剂sema (sema) 14mg QD可将主要不良心血管（CV）事件（MACE）风险降低14%。GLP-1RAs通常用于降低2型糖尿病（T2D）患者的A1c和BMI。口服sema的心血管益处是否受到基线A1c或BMI的影响尚不完全清楚。方法：SOUL的主要终点是到达首次MACE的时间，使用Cox回归通过基线A1c、BMI和体重进行事后分析评估。结果：T2D患者(n=9650；A1c 6.5-10%)和已知的动脉粥样硬化性CV疾病（ASCVD）或慢性肾脏疾病（CKD）随机分配到口服sema或安慰剂组，平均随访47.5个月。我们发现口服sema使用与基线A1c相关的MACE结果存在显著差异，A1c≤8.0%时效果更明显（图）。当进一步分析四个糖化血红蛋白层次的数据时，口服sema的MACE获益似乎适用于糖化血红蛋白7%的患者。口服sema对MACE的影响在BMI高于/低于30 kg/m2的人群中是相同的，在所有四个BMI层中，在平均体重（87.9 kg）以上/以下的人群中也是如此（图）。结论：在SOUL试验中，口服sema的CV益处在基线时A1c水平较高时更为明显，但在不同BMI类别中是一致的。这些数据可能有助于告知T2D、ASCVD和/或CKD患者口服sema的个体化使用。S.E. Inzucchi：顾问；诺和诺德、阿斯利康、勃林格殷格翰、默克辉瑞公司、拜耳制药公司R. Abdul Ghani：没有。J.迪恩菲尔德：其他关系；安进公司、阿斯利康公司、拜耳制药公司、勃林格殷格翰公司、默克公司；诺华制药公司、诺和诺德A/S、诺和诺德A/S、辉瑞公司M.D.M. Engelmann：雇员；诺和诺德公司。G. Hovingh：雇员；诺和诺德公司。股票/股东;诺和诺德公司。杰普森：没有。M. keller：咨询小组；雅培，拜耳制药公司演讲者的局;勃林格-殷格翰，强生&amp；约翰逊医疗器械公司。顾问小组;莉莉糖尿病。演讲者的局;莉莉糖尿病。顾问小组;诺和诺德公司。演讲者的局;诺和诺德公司。顾问小组;赛诺菲。K. Mandavya：雇员；诺和诺德公司。J.F. Mann：其他关系；阿斯利康，拜耳制药公司顾问小组;诺和诺德公司。董事会成员;阿斯利康，拜耳制药，勃林格殷格翰，诺和诺德。其他关系;赛诺菲。顾问;阿斯利康，拜耳制药公司，诺和诺德。研究支持;阿斯利康。其他关系;勃林格殷格翰集团。研究支持;诺和诺德，赛诺菲。演讲者的局;阿斯利康，拜耳制药公司，诺和诺德，诺华公司。其他关系;UpToDate Inc / KDIGO。马克思：发言人局；雅培，安进公司，阿斯利康。顾问小组;阿斯利康。演讲者的局;拜耳制药公司顾问小组;拜耳制药公司演讲者的局;勃林格殷格翰集团。顾问小组;勃林格殷格翰集团。演讲者的局;第一三共制药。顾问小组;默克夏普公司；Dohme公司发言人局；诺和诺德公司。顾问小组;诺和诺德公司。演讲者的局;赛诺菲。顾问小组;赛诺菲。演讲者的局;莉莉糖尿病。C. Mathieu：咨询小组；诺和诺德、赛诺菲、礼来、雅培、美敦力、SAB生物治疗公司、罗氏糖尿病护理、顶点制药、Biomea Fusion、拜耳制药公司。D.K. McGuire：顾问；诺和诺德公司。顾问小组;诺和诺德公司。顾问;礼来美国有限责任公司顾问小组；礼来美国有限责任公司顾问；勃林格殷格翰集团。顾问小组;Boehringer-Ingelheim, AstraZeneca, ESPERION Therapeutics, Inc., NewAmsterdam Pharma, Pfizer Inc.。顾问;应用治疗公司、Lexicon制药公司、拜耳制药公司、安进公司、Kailera、Idorsia、Alveus、Metsera。V. Mohan：发言人局；诺和诺德公司。顾问小组;阿伯特。研究支持;Servier实验室。演讲者的局;USV私人有限公司，赛诺菲，美敦力，礼来公司。S.L. Mulvagh：顾问小组；诺和诺德，默克；有限公司有限公司R. Pop-Busui：董事会成员；美国糖尿病协会。顾问;Averitas Pharma, Inc.研究支持;拜耳制药公司其他关系;生原体。研究支持;青少年糖尿病研究基金会（JDRF）。顾问小组;Lexicon制药公司，诺和诺德。研究支持;诺和诺德，国家糖尿病、消化和肾脏疾病研究所。顾问;罗氏诊断。N.R. Poulter：顾问；Servier Laboratories, Alnylam Pharmaceuticals, Inc。研究支持;Servier实验室。演讲者的局;阿斯利康。顾问;Aktiia。M. Ripa：雇员；诺和诺德公司。G. Roman：咨询小组；阿斯利康。顾问;Berlin-Chemie AG)。研究支持;阿斯利康。顾问小组;勃林格殷格翰，美敦力，礼来糖尿病，诺和诺德。研究支持;诺和诺德公司。顾问小组;罗氏糖尿病护理，赛诺菲，Viatris公司。R. Sánchez García：没有。谢彻特：没有。J.B.巴斯：其他关系；concept Therapeutics, Dexcom, Inc., Novo Nordisk。顾问;Altimmune, Amgen, ApStem, Aqua Medical, AstraZeneca, Boehringer-Ingelheim, CeQur, Eli Lilly and Company, embecta, GentiBio。其他关系;Glyscend疗法。顾问;胰岛素公司，美敦力公司。其他关系;糖尿病的健康。顾问;Metsera。其他关系;钟摆疗法，Praetego，稳定健康。顾问;Tandem Diabetes Care, Inc, TERNS Pharmaceuticals, Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S。融资诺和诺德A/S

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来源期刊

Diabetes 医学-内分泌学与代谢

CiteScore

12.50

自引率

2.60%

发文量

1968

审稿时长

1 months

期刊介绍： Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes. However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.