Empagliflozin

Bagsværd, Denmark, 29 March 2025 – Novo Nordisk today presented the full results from the SOUL cardiovascular outcomes trial, demonstrating that Rybelsus ® (oral semaglutide) significantly reduced the risk of major adverse cardiovascular events in adults with type 2 diabetes and cardiovascular disease (CVD) and/or chronic kidney disease (CKD) 1 . These new data from the phase 3b trial were featured during a late-breaking clinical trial session at the American College of Cardiology's (ACC) Annual Scientific Session and Expo in Chicago, US and simultaneously published today in New England Journal of Medicine 2 . The SOUL trial achieved its primary endpoint, demonstrating a 14% reduction in risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes and CVD and/or CKD when treated with Rybelsus ® compared to placebo. Each component of MACE, being CV death, nonfatal myocardial infarction and nonfatal stroke, contributed to the risk reduction 1 . “Heart attacks and strokes are the leading causes of disability and death for people with type 2 diabetes, and there is a need for new, patient-centric treatments to help manage this risk,” said Darren McGuire, MD, Distinguished Chair in Cardiovascular Science and Teaching Professor of Medicine at UT Southwestern, US, and SOUL steering committee co-chair. “The SOUL trial in adults with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) and/or CKD demonstrated significant reductions in the risk of major cardiovascular events including heart attack, stroke and CV death in those treated with oral semaglutide vs placebo. The proven cardiovascular benefit reflects a profound clinical impact for our patients who now have an oral option to improve health outcomes.” Cardiometabolic diseases span a wide range of conditions, including cardiovascular and peripheral artery disease, type 2 diabetes and chronic kidney disease 3 . When combined, these conditions represent the leading cause of death globally 4 . Having type 2 diabetes directly increases the risk of developing interconnected cardiometabolic diseases, while also contributing to the progression of other cardiovascular risk factors 5 . Nearly one in three adults with type 2 diabetes have CVD 6 . “Novo Nordisk continues to evolve its focus beyond diabetes and obesity towards a broader spectrum of metabolic and cardiovascular health,” said Martin Holst Lange, executive vice president for Development at Novo Nordisk. “These data, alongside our other data being presented at ACC, reinforce the comprehensive set of health benefits of semaglutide, making it a strong option for healthcare professionals addressing the spectrum of metabolic and cardiovascular health – and our continued leadership in the space.” The overall safety profile of oral semaglutide in SOUL was consistent with that seen in previous semaglutide trials, and no new safety signals were observed. The incidence of serious adverse events (SAEs) was lower in participants receiving Rybelsus ® than those receiving placebo, mostly due to the higher rate of cardiovascular events and infections in the placebo group. The most common SAEs were cardiac disorders (17.8% and 19.8%, respectively) and infections/infestations (15.0% and 16.5%, respectively) in the Rybelsus ® and placebo arms 1 . In a key secondary analysis from SOUL published simultaneously, oral semaglutide reduced risk of MACE independently of baseline use of SGLT2i and suggests similar benefits in participants with and without concomitant SGLT2i use during trial 7 . SOUL confirmed the well-established safety and tolerability profile of semaglutide supported by long-term safety data with more than 33 million patient years 8 . Based on data from the SOUL clinical trial, Novo Nordisk submitted a label extension application for Rybelsus ® , which has been accepted for review by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA. A decision is anticipated in 2025. About SOUL SOUL was a multicentre, international, randomised, double-blind, parallel-group, placebo-controlled, phase 3 cardiovascular outcomes trial with 9,650 people enrolled. It was conducted to assess the effect of oral semaglutide vs placebo on cardiovascular outcomes in people with type 2 diabetes and established CVD and/or CKD. The SOUL trial was initiated in 2019. The key objective of SOUL was to demonstrate that oral semaglutide lowers the risk of major adverse cardiovascular events (a composite endpoint consisting of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) compared to placebo, both added to standard of care in patients with type 2 diabetes and established CVD and/or CKD 9 ,10 . About Rybelsus ® Rybelsus ® (oral semaglutide) is a GLP-1 receptor agonist indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus to improve glycaemic control as an adjunct to diet and exercise 11,12 . Rybelsus ® is administered once daily and is approved for use in three therapeutic dosages: 3 mg, 7 mg and 14 mg 13,14 . Rybelsus ® offers superior blood glucose lowering vs Januvia ® and Jardiance ® 13,14 , together with consistent weight reduction 13-15 and reduction in cardiometabolic risk factors 15 . Rybelsus ® is currently commercially marketed in 45 countries. More than 2.1 million people with type 2 diabetes are currently being treated with Rybelsus ® worldwide 16 . About Novo Nordisk Novo Nordisk is a leading global healthcare company founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat serious chronic diseases built upon our heritage in diabetes. We do so by pioneering scientific breakthroughs, expanding access to our medicines and working to prevent and ultimately cure disease. Novo Nordisk employs about 76,300 people in 80 countries and markets its products in around 170 countries. Novo Nordisk's B shares are listed on Nasdaq Copenhagen (Novo-B). Its ADRs are listed on the New York Stock Exchange (NVO). For more information, visit novonordisk.com, Facebook , Instagram , X , LinkedIn and YouTube . Contacts for further information _______________________ References 1.   McGuire DK, et al. Oral presentation presented at the American College of Cardiology Congress Scientific Session & Expo 2025; 29–31 March 2025. Presentation 104-07. 2.   McGuire DK., et al. N Engl J Med. 2025, New England Journal of Medicine: https://www-nejm-org.libproxy1.nus.edu.sg/doi/full/10.1056/NEJMoa2501006 3.   Reiter-Brennan C, et al. Curr Cardiol Rep. 2021;23:22. 4.   World Health Organization [online]. Available at: https://www-who-int.libproxy1.nus.edu.sg/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds ) Last accessed: February 2025. 5.   Chakraborty S, et al. Clin Med Insights Endocrinol Diabetes. 2023;16:11795514231220780. 6.   Mosenzon O, et al. Cardiovasc Diabetol. 2021;20:154 7.   Marx N., et al. Circulation 2025: https://www-ahajournals-org.libproxy1.nus.edu.sg/doi/10.1161/CIRCULATIONAHA.125.074545 8.   Novo Nordisk data on file. 9.   NCT03914326. Available at: https://clinicaltrials.gov/ct2/show/NCT03914326 Last accessed: February 2025. 10.   McGuire DK, et al. Diabetes Obes Metab. 2023;25:1932–1941. 11.   Rybelsus ® (semaglutide) US PI. 2024 [online]. Available at: https://www.novo-pi.com/rybelsus.pdf Last accessed: March 2025. 12.   Rybelsus ® (semaglutide) SmPC. 2025 [online]. Available at: https://www.ema.europa.eu/en/documents/product-information/rybelsus-epar-product-information_en.pdf Last accessed: March 2025. 13.   Rodbard HW, et al. Diabetes Care . 2019;42:2272–2281. 14.   Rosenstock J, et al. JAMA. 2019;321:1466–1480. 15.   Husain M, et al. N Engl J Med. 2019;381:841–851. 16.   Novo Nordisk Data on File. IQVIA Ozempic and Rybelsus patient numbers March 2025.

点击“蓝字”关注我们 慢性肾脏病（CKD）是全球性的公共健康问题，在全球范围内影响着约8.5亿人，其患者面临着较高的死亡率风险，其中心血管事件是导致死亡的首要原因。钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）作为一种新型药物，在降低糖尿病患者心血管风险方面已显示出积极效果，但对于其在CKD患者中的作用尚存在不一致的研究结果。近期，一项系统综述和荟萃分析旨在全面评估SGLT2i对不同阶段CKD患者心血管死亡、全因死亡及主要不良心脏事件（MACE）的影响，为临床实践提供科学依据。 研究背景 CKD患者的心血管风险极高，其病理机制涉及慢性炎症、氧化应激、内皮功能障碍及代谢紊乱。尽管RAS抑制剂是CKD治疗的基石，但其对心血管事件的改善作用有限。SGLT2is最初作为降糖药开发，后续研究发现其可通过多机制（如降低容量负荷、改善能量代谢、抗纤维化等）减少心血管事件。然而，既往研究多聚焦于糖尿病或心力衰竭人群，CKD患者（尤其是非糖尿病或晚期CKD患者）的循证医学证据仍不充分。此外，不同基线肾功能（eGFR）和KDIGO风险分层的患者是否均能获益尚不明确。 因此，深入探究SGLT2i在CKD患者中的作用机制及其对不同阶段患者的影响，对于优化治疗策略、改善患者预后具有重要意义。 研究设计 本研究遵循PRISMA指南，系统检索了PubMed、Cochrane、Scopus和Web of Science数据库（截至2023年11月30日），纳入评估SGLT2is对CKD患者心血管死亡影响的随机对照试验（RCT），并报告根据基线肾功能分层的治疗效果。排除标准包括非随机对照研究、非成人研究等。 主要结局为心血管死亡，次要结局包括全因死亡及MACE。研究根据基线估算肾小球滤过率（eGFR）（≥60 vs. <60 mL/min/1.73m2）和KDIGO风险分类（低、中、高、极高风险）进行亚组分析，采用Cox比例风险模型计算风险比（HR），并通过随机效应模型合并数据。 核心结果 1. 纳入研究与患者特征 共纳入11项RCT（83 203例患者），涵盖达格列净、恩格列净、卡格列净等多种SGLT2is。研究人群包括糖尿病和非糖尿病患者，基线eGFR范围为20~90 mL/min/1.73m2，中位随访时间16个月至4.2年。 2. 心血管死亡风险 共纳入10项RCTs，共74 957例患者。结果显示，SGLT2is显著降低心血管死亡风险14%（HR 0.86，95%CI：0.79~0.94）（图1），各eGFR亚组（≥60 mL/min/1.73m2：HR 0.82，95%CI：0.65~1.02；<60 mL/min/1.73m2：HR 0.86, 95%CI：0.77~0.96；P亚组差异=0.68）及KDIGO风险分层效果一致（P亚组差异=0.69）。 图1. SGLT2i对CKD患者心血管死亡的影响 3.全因死亡风险 共纳入9项RCTs，共68 694例患者。结果显示，SGLT2is显著降低心血管死亡风险15%（HR 0.85，95%CI：0.79~0.91）（图2），且在KDIGO分类为极高风险的患者中效果更显著（HR 0.69，95%CI：0.55~0.86）。 图2. SGLT2i对CKD患者全因死亡的影响 4.MACE风险 在8个研究68 466例患者中评估SGLT2i对MACE的影响。结果显示，SGLT2is降低13%的MACE风险（HR 0.87，95%CI：0.81~0.93）（图3），各药物类型（卡格列净、达格列净等）效果无显著差异。 图3. SGLT2i对CKD患者MACE的影响 结论 该研究结果表明，SGLT2i治疗能够显著降低不同阶段CKD患者的心血管死亡和全因死亡风险，且对 MACE 也有显著的预防作用。这些发现支持SGLT2i作为CKD患者心血管保护治疗的常规用药，无论患者处于CKD的哪个阶段或使用何种类型的SGLT2i，均能获得一定的益处，尤其是在心血管高风险患者中，其效果可能更为显著。 讨论 SGLT2i在CKD患者中展现出的积极心血管保护作用可能与其多重机制有关。一方面，通过改善血糖控制、促进体重减轻和降低血压，间接降低了心血管风险因素；另一方面，其直接的心血管保护作用可能涉及增加酮体生成、抑制促炎、氧化和促纤维化因子、改善自噬、减少心肌Na+/H+交换以及降低心包脂肪质量等机制。此外，SGLT2i的肾脏保护作用，如减少蛋白尿和延缓CKD进展，也可能在一定程度上解释了其对心血管和全因死亡风险的降低作用。然而，需要注意的是，尽管该研究结果具有统计学意义和较高的证据质量，但在实际临床应用中，仍需考虑患者的个体差异、合并症以及药物的耐受性和安全性等因素，以制定更为精准的治疗方案。 总结 综上所述，SGLT2i在CKD患者治疗中具有重要的临床价值，能够有效降低心血管和全因死亡风险，为改善CKD患者的预后提供了新的治疗选择。未来需进一步探索非糖尿病CKD人群的长期效果及机制，并推动指南更新以优化临床实践。通过多学科协作，SGLT2is有望成为CKD综合管理的重要组成部分，最终改善患者预后与生活质量。 参考文献：Karagiannidis AG, et al. Eur J Clin Invest. 2025; 55: e14335. 声明：本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。 最新《心肾代谢时讯》读者专属微信交流群建好了，快快加入吧！扫描左边《心肾代谢时讯》小助手二维码（微信号：CKM-Times），回复“心肾代谢读者”，ta会尽快拉您入群滴！ （来源：《心肾代谢时讯》编辑部） 版权声明 版权属《心肾代谢时讯》所有。欢迎个人转发分享。其他任何媒体、网站未经授权，禁止转载。