Ianalumab

点击“蓝字”关注我们编者按几项著名的糖尿病大型循证医学试验均未能证实严格的血糖控制能降低发生糖尿病大血管并发症的风险，这使得人们对“降糖治疗是否依然是2型糖尿病心血管并发症管理的核心”的概念心存疑虑。在5月16~18日杭州举办的2025内分泌代谢疾病前沿进展学术会议（CDEF 2025）上，大庆研究核心引领者、卫健委中日友好医院李光伟教授针对这一疑问，基于大庆研究30年随访及UKPDS 40年数据指出，早期强化血糖控制的“遗留效应”可使心血管并发症获益在干预期结束后多年依然存在。这提醒早期打断“糖化-氧化-动脉硬化”心血管事件链仍是2型糖尿病心血管病防治的重要策略，为降糖治疗的核心地位提供了新的循证依据。从UKPDS辉煌到CVOT困境，严格降糖在心血管保护中遭“冷遇”？近年来，随着降糖药物种类扩充和临床研究证据的积累，2型糖尿病（T2DM）的治疗理念不断革新，降糖治疗的意义何在？它是否依然是T2DM心血管并发症管理的核心？对这个问题，许多人心存疑惑。中华医学会糖尿病学分会第二十六次学术会议上，美国糖尿病协会（ADA）2014年Banting奖得主Rury Holman教授报告了英国前瞻性糖尿病研究（UKPDS）随访40年的结局。这一报告提醒临床医师应对T2DM早期血糖控制与长期心血管疾病（CVD）结局的影响予以关注。UKPDS研究是循证医学问世之前开展的一项里程碑式随机对照临床试验（RCT），入选5102例新诊断T2DM患者。全部研究及随访研究历时40余年，即为期20年（1977~1997年）的RCT期、10年（1997~2007年）的RCT后随访期以及14年（2007~2021年）的扩展RCT后随访期。UKPDS研究RCT期（1997年）结果显示，与常规血糖控制组相比，磺脲类或胰岛素强化治疗组微血管并发症风险显著下降，而降低心肌梗死的有效性未得到证实（降低16%，P=0.052），但是二甲双胍强化血糖控制组任何糖尿病相关终点风险显著下降32%（P=0.0023）、全因死亡风险下降36%（P=0.011）、心肌梗死风险下降39%（P=0.010）[1]。UKPDS研究和DCCT研究一起成就了降糖治疗能降低CVD风险的辉煌，使“糖化-氧化-动脉硬化”的理论深入人心。人们坚信，紧急降血糖在糖尿病酮症酸中毒（DKA）时可挽救生命，而长期控制血糖的目的是降低其后数年乃至数十年大小血管事件风险。在以上两项研究成果的鼓舞下，更严格的降糖成为糖尿病学界的努力方向。因为0.052的P值离达到显著统计学意义（P<0.05）十分接近，人们对更严格的血糖控制能成功降低糖尿病患者大血管并发症风险充满期待。人们的假设是降低大血管并发症的血糖值可能比降低微血管并发症更严格，于是HbA1c 6.5%成为血糖控制治疗追求的新目标。以ACCORD、VADT和ADVANCE研究为代表的循证医学研究目标都指向比UKPDS研究更严格的血糖控制以求降低大血管并发症风险。出乎意外的是，这几个大型临床研究全部为阴性结果，均没有证实更严格的血糖控制能获得良好的CVD结局[2-4]。2007年世界著名心血管病专家Steven Nissen发表的罗格列酮Meta分析显示其可增加T2DM心梗风险（HR=1.43，95%CI：1.03~1.98，P=0.03）[5]，引发学界哗然。FDA此后做出决定要求所有新开发的降糖药物必须开展心血管结局研究（CVOT），这一政策改变了T2DM管理格局。后续二肽基肽酶-4（DPP-4）抑制剂试验亦未显示明显心血管获益[6]，进一步动摇了学界对降糖治疗心血管保护的信心。保障降糖药物不增加心血管风险成了主要任务。无独有偶，同期的降脂、降压研究几乎都取得了阳性结果，降糖对防治CVD的无用论更加流行，以致糖尿病学界的大咖们也不得不承认，缺乏循证医学证据支持降糖的心血管获益，“糖化-氧化-动脉硬化”理论也随之遇冷。UKPDS+大庆研究最新成果再掀风潮：确证早期控糖为核心的重要性！01.血糖的遗留效应与T2DM血糖控制的心血管获益糖化-氧化致动脉硬化理论是真理还是缪误？临床医师过去所长期坚持的降糖治疗真的对降低心血管风险无益？UKPDS研究40年随访结局：RCT阶段结束后受试者均恢复常规管理，40年随访发现强化血糖控制组的心血管获益仍持续存在[7]，Rury Holman教授基于UKPDS研究指出，早期强化降糖可减少CVD并发症，且于干预结束后10年和延伸随访24年间获益持续。因此，确诊后尽快实现血糖水平正常，似乎具有永久性获益。这种现象被称为“遗留效应（legacy effect）”。他还强调，血糖遗留效应的关键是确诊时的高血糖而非低血糖，持续高血糖可能引发长久且不可逆的代谢变化，以致终生面临并发症高发的风险，即使以后得到较好治疗，也难以显现早期治疗的全部获益。因此，一旦确诊，尽早治疗并维持接近正常的血糖水平，才能最大限度地降低并发症风险。后续研究差异或与人群特征相关：UKPDS研究纳入初诊且相对较年轻的糖尿病患者并观察到心血管获益；而后续的ACCORD、VADT和ADVANCE研究对象多为长病程、高龄患者，未显示获益。人们似乎领悟到“银发一族”晚期降糖治疗未能降低心血管风险的故事可能不会在年轻糖尿病人群中重演，并开始将注意力转移到相对年轻的长病程糖尿病患者。如人们所预料，ACCORD研究后续分析在糖尿病亚组（基因分型）中发现强化降糖治疗可降低长期死亡风险[7]。以上种种迹象表明，糖尿病合并CVD人群存在高度异质性，需个体化、精准化血糖管理提高心血管获益。新型降糖药物如胰高糖素样肽-1受体激动剂（GLP-1RA）和钠-葡萄糖共转运蛋白2抑制剂（SGLT-2i）因强效降糖且低血糖风险低，为尽早安全降糖提供了新的可能。02.以血糖控制为核心的T2DM防治对心血管病管理的重要价值以GLP-1RA及SGLT2i为代表的新型降糖药物因兼具强效降糖、减重及心肾保护作用，其CVOT研究推动欧美指南对T2DM的管理更聚焦于靶器官保护。这不禁令人深思——血糖控制在T2DM治疗中的地位是否已经弱化？应该说，答案是否定的，血糖控制仍然是T2DM管理的核心。UKPDS研究首当是早期血糖控制重要性的有力证据。其中，UKPDS 88研究结果显示，相比延迟血糖控制，早期血糖控制带来的全因死亡及心肌梗死获益更显著[1]。新发表的UKPDS 91研究表明，在长达40年的随访后，与传统血糖控制相比，早期强化血糖控制（磺脲类或胰岛素）较传统血糖控制，全因死亡风险降低10%（95%CI：2%~17%；P=0.015），心肌梗死风险降低17%（95%CI：6%~26%；P=0.002）[7]，新诊T2DM患者早期控糖可带来长期获益。我国大庆糖尿病预防研究的34年随访从预防角度支持这一结论：6年生活方式干预使未进展为糖尿病者，后续24年全因死亡和心脑血管事件风险降低40%[9]，提示早期干预糖尿病前期高血糖状态可降低长期心血管风险。以上两项著名研究的新结果从糖尿病降糖治疗及糖尿病前期推迟血糖升高两方面证实：早期打断“糖化-氧化-动脉硬化”心血管事件链可带来长期心血管获益，血糖控制在T2DM心血管风险管理中的重要性不容忽视。动脉粥样硬化的进展是一个多步骤的过程，与糖尿病患者的高血糖、血脂异常、AGE（高级糖化终产物）及炎症密切相关。AGE通过损伤血管内皮细胞、诱导血管平滑肌细胞（VSMC）异常增殖迁移及表型转化（成骨/巨噬细胞样）等机制加速病变进展，而抑制AGE-RAGE（AGE受体）轴可延缓或改善病情[10,11]。提示早期干预代谢异常打断“糖化-氧化-动脉硬化”心血管事件链对阻断糖尿病心血管风险至关重要。结语UKPDS降糖研究40年和大庆研究34年长期随访结果均表明，将上述这一理论转化为临床实践是一项长期且艰巨的任务。改善代谢、兼顾减重和降糖的新型降糖药物的出现或将助力实现这一目标。专家简介李光伟 教授中日友好医院 教授，主任医师中日友好医院国际医疗部名誉主任，内分泌首席专家中国医学科学院阜外医院内分泌与心血管病诊治中心主任主要研究领域是糖尿病及其心脑血管疾病控制和预防其参与和主持的中国大庆糖尿病预防研究被称为世界糖尿病预防研究的里程碑SCI论文总引用次数逾6900次参考文献（上下滑动可查看）[1] Lind M, Imberg H, Coleman RL, et al. Historical Hba(1c) Values May Explain the Type 2 Diabetes Legacy Effect: UKPDS 88[J]. Diabetes Care, 44(10): 2231–2237. DOI: 10.2337/dc20-2439.[2] Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes[J]. N Engl J Med, 2008, 358(24): 2545-2559. DOI: 10.1056/NEJMoa0802743. [3] Reaven PD, Moritz TE, Schwenke DC, et al. Intensive glucose-lowering therapy reduces cardiovascular disease events in veterans affairs diabetes trial participants with lower calcified coronary atherosclerosis[J]. Diabetes, 2009, 58(11): 2642-2648. DOI: 10.2337/db09-0618. [4] Zoungas S, Chalmers J, Ninomiya T, et al. Association of HbA1c levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds[J]. Diabetologia, 2012, 55(3): 636-643. DOI: 10.1007/s00125-011-2404-1. [5] Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356(24):2457-2471.DOI: 10.1056/NEJMoa072761[6] Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus[J]. N Engl J Med, 2013, 369(14):1317-1326.DOI: 10.1056/NEJMoa1307684.[7] Adler AI, Coleman RL, Leal J, et al. Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91)[J]. Lancet, 2024, 404(10448): 145-155. DOI: 10.1016/S0140-6736(24)00537-3. [8] Mariam A, Miller-Atkins G, Pantalone KM, et al. A type 2 diabetes subtype responsive to accord intensive glycemia treatment[J]. Diabetes Care, 2021,44(6): 1410-1418.DOI: 10.2337/dc20-2700.[9] Qian X, Wang J, Gong Q, et al. Non-diabetes status after diagnosis of impaired glucose tolerance and risk of long-term death and vascular complications: a post hoc analysis of the Da Qing diabetes prevention outcome study[J]. PLoS Med,2024, 21(7):e1004419.DOI: 10.1371/journal.pmed.1004419.[10] Mao L, Yin R, Yang L, et al. Role of advanced glycation end products on vascular smooth muscle cells under diabetic atherosclerosis. Front Endocrinol (Lausanne). 2022, 13: 983723. DOI: 10.3389/fendo.2022.983723. [11] Wang B, Jiang T, Qi Y, et al. AGE-RAGE axis and cardiovascular diseases: pathophysiologic mechanisms and prospects for clinical applications[J]. Cardiovasc Drugs Ther, 2024 Nov 5. DOI: 10.1007/s10557-024-07639-0.文章撰写整理:许菁、李光伟教授，本文稍有调整声明：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《国际糖尿病》读者专属微信交流群建好了，快快加入吧！扫描左边《国际糖尿病》小助手二维码（微信号：guojitnb），回复“国际糖尿病读者”，ta会尽快拉您入群滴！（来源：《国际糖尿病》编辑部）版权声明版权属《国际糖尿病》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。

NATALEE subanalysis evaluates Kisqali in pre-menopausal early breast cancer patients, amid rising diagnosis rates in younger patients Pluvicto analysis and Scemblix ASC4START primary endpoint results provide insights into use in earlier settingsFabhalta APPULSE-PNH full results build on Phase III program, reporting new data from expanded PNH population in adults switching from anti-C5Ianalumab Phase II data in immune thrombocytopenia and longer-term pelabresib Phase III data in myelofibrosis show breadth of pipeline in hematologic diseases Basel, May 15, 2025 – Novartis will present data from 60 company or investigator sponsored abstracts that have the potential to change clinical practice, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and the European Hematology Association (EHA) 2025 Congress. “The breadth of our oncology and hematology portfolio – anchored by Kisqali, Pluvicto, Scemblix and Fabhalta – demonstrates our leadership in both solid tumors and hematologic diseases,” said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis. “At ASCO and EHA, we will present new data on these priority medicines as well as updates from our pipeline and our industry-leading radioligand therapy research.” Novartis will also highlight its US partnerships with the National Football League (NFL), Alliance for Breast Cancer Policy, and ZERO Prostate Cancer, which encourage people to make proactive decisions about their health and advance patient-centered policy solutions to help improve outcomes. “We're witnessing a profound shift in how people move through their cancer journey, with cancer diagnoses occurring at younger ages and, simultaneously, older patients living longer and approaching aging with new vigor,” said Victor Bultó, President, US, Novartis. “As a leader in driving medical advances in oncology, we have the responsibility to also make a difference in areas beyond treatment innovation. By partnering across the ecosystem, our goal is to advance the conversation around earlier detection and meet the evolving needs of this next generation of cancer patients.” Key highlights of data accepted by ASCO include: Medicine Abstract Title Abstract Number/ Presentation Details Kisqali®(ribociclib)* Efficacy and safety of ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in NATALEE: Analysis across menopausal status and age Abstract #516Rapid OralJune 1, 8:00 – 9:30am CDT Kisqali®(ribociclib) Real-world (RW) analysis of characteristics and risk of recurrence (ROR) in Black patients (pts) with HR+/HER2− early breast cancer (EBC) eligible for NATALEE Abstract #527Poster PresentationJune 2, 9:00am – 12:00pm CDT Kisqali®(ribociclib) Adjuvant WIDER: A phase 3b trial of ribociclib (RIB) + endocrine therapy (ET) as adjuvant treatment (tx) in a close-to-clinical-practice patient (pt) population with HR+/HER2− early breast cancer (EBC) Abstract #TPS617Poster PresentationJune 2, 9:00am – 12:00pm CDT Kisqali®(ribociclib) First-line (1L) ribociclib (RIB) + endocrine therapy (ET) vs combination chemotherapy (combo CT) in clinically aggressive hormone receptor (HR)+/HER2− advanced breast cancer (ABC): A subgroup analysis of patients (pts) with or without liver metastases (mets) from RIGHT Choice Abstract #1069Poster PresentationJune 2, 9:00am – 12:00pm CDT Scemblix®(asciminib) Efficacy and safety of asciminib (ASC) in patients (pts) with chronic-phase chronic myeloid leukemia (CML-CP) after 1 tyrosine kinase inhibitor (TKI): Interim analysis (IA) of the phase 2 ASC2ESCALATE trial Abstract #6516Rapid OralMay 30, 1:00 – 2:30pm CDT Scemblix® (asciminib) Primary endpoint results of the phase 3b ASC4START trial of asciminib (ASC) vs nilotinib (NIL) in newly diagnosed chronic phase chronic myeloid leukemia (CML-CP): Time to treatment discontinuation due to adverse events (TTDAE) Abstract #6501Oral PresentationJune 2, 3:00 – 6:00pm CDT Pluvicto®(lutetium Lu 177 vipivotide tetraxetan) Clinical outcomes of prompt versus deferred 177Lu-PSMA-617 initiation for metastatic castration-resistant prostate cancer (mCRPC) based on prior androgen receptor pathway inhibitor (ARPI) and taxane chemotherapy exposure: a real-world PRostatE Cancer dISease observatION (PRECISION) data platform analysis Abstract #e17030Online Publication Pluvicto®(lutetium Lu 177 vipivotide tetraxetan) Real-world outcomes among patients with metastatic castration-resistant prostate cancer (mCRPC) receiving guideline-recommended therapies after treatment with 177Lu-PSMA-617: a real-world PRostatE Cancer dISease observatION (PRECISION) data platform analysis Abstract #e17035Online Publication Pluvicto®(lutetium Lu 177 vipivotide tetraxetan) PSMA-delay castration (DC): An open-label, multicenter, randomized phase 3 study of [177Lu]Lu-PSMA-617 versus observation in patients with metachronous PSMA-positive oligometastatic prostate cancer (OMPC) Abstract #TPS5127Poster PresentationJune 2, 9:00am – 12:00pm CDT Key highlights of data accepted by EHA include: Medicine Abstract Title Abstract Number/ Presentation Details Fabhalta®(iptacopan) APPULSE-PNH: Oral iptacopan monotherapy demonstrates clinically meaningful hemoglobin (Hb) increases in patients (pts) with paroxysmal nocturnal hemoglobinuria (PNH) and Hb ≥10 g/dL on anti-C5 therapy Abstract #S183Oral PresentationJune 13, 5:00 – 6:15pm CEST Fabhalta®(iptacopan) The 2-year safety and efficacy of iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria (PNH) from APPLY- and APPOINT-PNH studies who entered the roll-over extension program (REP) Abstract #PF660Poster PresentationJune 13, 6:30 – 7:30pm CEST Scemblix®(asciminib) Asciminib (ASC) shows superior tolerability vs nilotinib (NIL) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): Primary endpoint results of the phase (Ph) 3b ASC4START trial Abstract #S166Oral PresentationJune 13, 5:00 – 6:25pm CEST Scemblix®(asciminib) Improved patient-reported outcomes (PROs) with asciminib (ASC) vs investigator-selected tyrosine kinase inhibitors (IS-TKIs) in newly diagnosed chronic myeloid leukemia (CML): ASC4FIRST wk 48 analysis Abstract #PS1588Poster PresentationJune 14, 6:30 – 7:30pm CEST Scemblix®(asciminib) Interim analysis (IA) results from ASC2ESCALATE support asciminib (ASC) as a treatment (Tx) option in chronic-phase chronic myeloid leukemia (CML-CP) after 1 tyrosine kinase inhibitor (TKI) Abstract #PF595Poster PresentationJune 13, 6:30 – 7:30pm CEST Pelabresib(DAK539) Pelabresib in combination with ruxolitinib for janus kinase inhibitor-naive patients with myelofibrosis: 72-week follow-up with long-term efficacy outcomes of the phase III MANIFEST-2 study Abstract #S223Oral PresentationJune 12, 5:00 – 6:15pm CEST Ianalumab(VAY736) A Phase 2 Study of Ianalumab in patients with primary immune thrombocytopenia previously treated with at least two lines of therapy (VAYHIT3) Abstract #S312Oral PresentationJune 15, 11:00am – 12:15pm CEST Rapcabtagene autoleucel (YTB323) Rapcabtagene Autoleucel (YTB323) in patients with relapsed/refractory diffuse large B-cell lymphoma: A phase II trial clinical update Abstract #PF1152Poster PresentationJune 13, 6:30 – 7:30pm CEST Novartis in oncologyThe Novartis oncology strategy focuses on people living with cancer and those who care for them, from loved ones to clinical care teams, including their providers. For the past 30+ years, the aim has been to extend and improve lives by discovering differentiated, innovative and practice-changing medicines for patients. As Novartis reimagines medicine, it collaborates with a wide range of patient advocacy groups and supports education, early cancer screening and diagnosis, all while innovating at a rate that is unparalleled in the industry. With approximately 35 research and development projects across solid tumors, hematology and radioligand therapy (RLT), Novartis is committed to using technology, leading science and patient-centered research to deliver pioneering cancer care for all those in need. DisclaimerThis press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. 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There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About Novartis Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach nearly 300 million people worldwide. Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram. # # # *Kisqali was developed by Novartis under a research collaboration with Astex Pharmaceuticals. Novartis Media RelationsE-mail: media.relations@novartis.com Novartis Investor RelationsCentral investor relations line: +41 61 324 7944E-mail: investor.relations@novartis.com