The availability of Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) has dramatically altered the management of heart failure (HF) patients, independently of their ejection fraction and glycemic status. A meta-analysis of 57 studies comparing SGLT2-I monotherapy vs. placebo or active comparator showed reductions in major cardiovascular events, but no impact on atherothrombotic events. In fact, a non-significant increase in the risk for non-fatal stroke was observed. Similar trend observed in multiple trials indicate a SGLT2-i class effect. Sotagliflozin is the first dual SGLT1/2 receptor inhibitor, that was shown to significantly reduce atherothrombotic events compared with placebo in diabetic HF patients, suggesting that dual SGLT1/2 inhibitor may have additional properties vs. SGLT2-i. The hypothesis of this study is that dual SGLT1/2 inhibition by sotagliflozin improves thrombogenic profile (i.e. reduces thrombus formation), which could make it a safer and more effective treatment option for cardiovascular (CV) patients than SGLT2-i. To test the hypothesis, the researchers will compare the antithrombotic activity of sotagliflozin vs. empagliflozin in healthy volunteers using a randomized, cross-over study design, where each participant will receive both study treatments (sotagliflozin and empagliflozin) separated by a washout period. Treatment effects will be assessed by measuring ex vivo thrombus formation using the Badimon Perfusion chamber, platelet aggregation using Multiplate Analyzer, and Thromboelastometry using RoTEM Gamma. Study assessments will be performed before initiating (baseline/pre-treatment) and after completion of each treatment.

开始日期2025-02-25

申办/合作机构

Icahn School of Medicine at Mount Sinai

NCT06147232

/ Not yet recruiting临床2期IIT

Prevention of CKD Progression in Type 1 Diabetes With Long Term Use of SGLTi Avoiding Kidney hypOxia(PLUTO)

Background: Sodium-glucose-cotransporter (SGLT) inhibition has been observed to reduce risk of cardiovascular events and kidney failure in persons with type 2 diabetes. People with type 1 diabetes also have increased risk of cardiovascular and kidney disease, and may benefit from SGLT-inhibition. The exact mechanism of how SGLT-inhibition benefits the kidneys are yet unknown. Change in renal hypoxia may be a factor.
Objective: The primary aim of this study is to assess the effects of 12 weeks SGLT-1 and 2 inhibition on renal oxygenation in persons with type 1 diabetes and chronic kidney disease.
Further aims are to study if renal oxygen consumption and response to SGLT-inhibition differs between people of African-Caribbean or Northern European decent.
Additionally effects on left ventricular ejection fraction, kidney function and biomarkers in blood and urine will be explored.
Method: 12 weeks treatment with oral sotagliflozin or matching placebo as intervention. Kidney oxygenation and perfusion parameters and left ventricular ejection fraction will be assessed by functional magnetic resonance imaging. Kidney function and biomarkers will be assessed according to local hospital laboratory guidelines.
Design: Randomized, double-blinded, placebo-controlled, cross over intervention study.
Study population: 69 persons with type 1 diabetes and diabetic kidney disease with albuminuria will be included, 39 at Steno Diabetes Center Copenhagen, 30 at King's College London.
Endpoints: Primary end-point: Change from 0 to 12 weeks in dynamic R2*-weighted signal after treatment with sotagliflozin compared to placebo. Secondary endpoints: Change from 0 to 12 weeks with sotagliflozin compared with placebo on renal perfusion, renal artery flow, renal oxygen consumption, renal parenchymal triglyceride fraction, renal fibrosis, left ventricular ejection fraction, urinary albumin-creatinin ratio, ketone bodies, erythropoietin, pro brain natriuretic peptide, and plasma- and urine inflammation- and fibrosis biomarkers as well as difference after 12 weeks treatment in glomerular filtration rate.
Timeframe: Inclusion of patients from february 2024. Last visit september 2025. Presentation spring 2026, publication fall 2026.

开始日期2025-02-01

申办/合作机构

Steno Diabetes Center A/S

[+4]

NCT06435156

/ Recruiting临床2期IIT

A Phase 2 Double-blind Randomised Controlled Trial Studying the Effect of Sotagliflozin Versus Placebo in Individuals with Heart Failure and Type 1 Diabetes.

People with type 1 diabetes sometimes develop heart failure which can cause symptoms like breathlessness, tiredness or ankle swelling, reduced quality of life and lead to being admitted to hospital or suffering potential fatal consequences. This trial is investigating if a tablet called sotagliflozin, can improve quality of life in people with type 1 diabetes and heart failure. In addition, this trial will also assess the safety and tolerability of sotagliflozin in this population.
In previous trials that included people with type 2 diabetes and heart failure sotagliflozin was shown to improve patients' symptoms of heart failure, quality of life and reduce the chance of people with heart failure being admitted to hospital or dying. However, people with type 1 diabetes and heart failure were not included in these trials meaning that it is not known if these benefits also apply to this population.
This trial aims to recruit 320 people with type 1 diabetes and heart failure symptoms in multiple sites in the United Kingdom (UK). This trial will compare the health and quality of life of participants who take sotagliflozin tablets with participants who take placebo tablets, which is a dummy tablet that looks the same as sotagliflozin. Participants will be randomly allocated to one of two groups (i.e. one taking sotagliflozin and the other the placebo) and both the medical team and participants will not know in which group each participant is until the end of the study. Participants will be in the trial for approximately 6 months and will be given sotagliflozin or placebo tablets to take 1 per day for 4 months. The trial is expected to run for a total of 26 months.

开始日期2025-01-28

申办/合作机构

University Of Dundee

[+2]

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332

项与索格列净相关的文献（医药）

2025-04-01·Physiological Reports

Effects of sotagliflozin on kidney and cardiac outcome in a hypertensive model of subtotal nephrectomy in male mice

Article

作者: Lopez, Natalia ; Zemljic‐Harpf, Alice ; Galdino, Ony Araujo ; Goodluck, Helen ; Vallon, Volker ; Kanoo, Sadhana ; Kim, Young Chul

Abstract:

Dual inhibition of sodium glucose cotransporters 1 and 2 (SGLT1/SGLT2) by sotagliflozin protects the kidney and heart in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). To gain mechanistic insights, the current study aimed to establish a murine model of hypertensive CKD that shows cardio‐renal protection by sotagliflozin. Since protection by SGLT2 inhibitors can be diabetes‐independent, a nondiabetic murine model of subtotal nephrectomy with angiotensin II infusion‐facilitated hypertension was followed for 7 weeks. The model showed 40% lower GFR, doubling in plasma FGF23, 50 mmHg higher systolic blood pressure (SBP), 100‐fold increased albuminuria, and robust signs of kidney injury, inflammation, and fibrosis versus sham controls, associated with a 30% larger left cardiac ventricle and wall thickness and upregulation of markers of cardiac overload and fibrosis. Sotagliflozin, initiated 1 week after the last surgery, showed target‐engagement evidenced by glucosuria, 9 mmHg lower SBP, temporal reduction in body weight and GFR, and 30% higher plasma GLP1. Sotagliflozin, however, did not improve markers of kidney injury, inflammation, fibrosis, albuminuria, and plasma FGF23, or signs of cardiac overload, fibrosis, or impaired function. Limited sotagliflozin responsiveness may relate to short treatment time, limited metabolic benefits in nondiabetic setting and/or the model's dominant angiotensin II‐driven effects/hypertension.

2025-04-01·ESC Heart Failure

Meta‐analysis of sotagliflozin, a dual sodium‐glucose‐cotransporter 1/2 inhibitor, for heart failure in type 2 diabetes

Review

作者: Philip, Sam ; Bantounou, Maria Anna ; Kaczmarek, Justyna ; Black Boada, Daniel ; Plascevic, Josip ; Sardellis, Panagiotis ; Awaes‐Mahmood, Ribeya ; Thuemmler, Rosa

Abstract:

Sodium‐glucose co‐transporters (SGLTs) mediate sodium and glucose transport across cell membranes. SGLT2 inhibitors have a recognized place within heart failure (HF) guidelines. We evaluated the effect of sotagliflozin on HF and cardiovascular outcomes in participants with type 2 diabetes. Scopus, Medline, Embase and Central were searched from inception until 2 June 2023. Randomized controlled trials evaluating sotagliflozin in type 2 diabetes participants and reporting HF events were selected. Major adverse cardiovascular events (MACE) and systolic blood pressure were evaluated. The Cochrane risk of bias tool (RoB 2.0) was used. Pooled mean difference (MD), relative risk (RR), 95% confidence intervals and the number needed to treat (NNT) were estimated (PROSPERO: CRD42023432732). We selected nine studies (n = 15 320 participants: n = 8040 intervention and n = 7280 control). The median follow‐up was 13.4 months (Q1 = 13, Q3 = 21). One study recruited participants with HF at baseline. After a follow‐up of >52 weeks, sotagliflozin significantly reduced the risk of HF [n = 8 studies; RR = 0.66 (0.64, 0.69)], stroke [n = 6 studies; RR = 0.75 (0.58, 0.97)] and MACE [n = 8 studies; RR = 0.73 (0.66, 0.81)]. The NNT was 20 and 26 for HF and MACE, respectively. Sotagliflozin lowered systolic blood pressure [n = 7; MD = −2.38 mmHg (−2.79, −1.97)]. No dose‐dependent effect was identified for HF [200 mg: RR = 0.38 (0.16, 0.89), 400 mg: RR = 0.57 (0.39, 0.85), P‐value = 0.22]. The high risk of bias was a limitation of this review. Sotagliflozin reduced HF and cardiovascular events in type 2 diabetes participants. Research exploring its effects in HF and comparisons with SGLT2 inhibitors is warranted to determine if dual SGLT inhibition surpasses selective inhibition.

2025-04-01·ESC Heart Failure

Effects of sodium–glucose co‐transporter inhibitors on individual clinical endpoints and quality of life

Article

作者: Kiuchi, Márcio G. ; Templin, Christian ; Meyer, Christian ; Chen, Shaojie ; Liu, Shaowen ; Ebrahimi, Ramin ; Liao, Jia ; Schmidt, Boris ; Acou, Willem‐Jan ; Derndorfer, Michael ; Heukäufer, Matthias ; Chun, Julian K. R. ; Niel, Johannes ; Martinek, Martin ; Ebrahimi, Fahim ; Futyma, Piotr ; Empen, Klaus ; Yin, Yuehui ; Chamling, Bishwas ; Janschel, Sarah ; Dörr, Marcus ; Schratter, Alexandra ; Ling, Zhiyu ; Pürerfellner, Helmut ; Sommer, Philipp ; Chen, Yang ; Di Vece, Davide ; Hummel, Astrid

Abstract:

Aims:

Sodium–glucose co‐transporter inhibitors (SGLTis) have cardiovascular protective effects. We aimed to assess the effects of SGLTis on individual hard clinical endpoints and quality of life (QoL) in patients with cardiovascular risk factors.

Methods and Results:

Data was searched in PubMed, Embase, Cochrane Library and clinicaltrials.gov databases up to February 2024. Randomized controlled trials (RCTs) comparing SGLTis with placebo were included. The primary outcomes were individual hard clinical endpoints (Subset A) and QoL (Subset B). For Subset A, 13 RCTs including 90 413 patients were enrolled (age 66 ± 10.1 years, 35.7% female, follow‐up 2.4 ± 0.3 years); as compared with placebo, SGLTis were associated with significantly lower risk of all‐cause mortality [risk ratio (RR): 0.90, 95% confidence interval (CI): 0.86–0.94, P < 0.01], cardiovascular mortality (RR: 0.87, 95% CI: 0.82–0.92, P < 0.01), hospitalization for heart failure (HF) (RR: 0.72, 95% CI: 0.68–0.76, P < 0.01), HF events (RR: 0.72, 95% CI: 0.68–0.75, P < 0.01), hospitalization for any cause (RR: 0.91, 95% CI: 0.88–0.93, P < 0.01) and myocardial infarction (MI) (RR: 0.92, 95% CI: 0.85–0.99, P = 0.03). Notably, the favourable effect of SGLTis on all‐cause mortality was more pronounced in younger (<65 years) patients (RR: 0.86, 95% CI: 0.81–0.92) and in studies with less female (RR: 0.84, 95% CI: 0.79–0.90). The favourable effect of SGLTis on MI was only observed in patients who received sotagliflozin (RR: 0.47, 95% CI: 0.31–0.73). For Subset B, nine RCTs including 2552 HF patients were enrolled (age 67.8 ± 12.4 years, 36.4% female, follow‐up 3.4 ± 1.9 months); SGLTis were associated with significant improvement in QoL as compared with placebo.

Conclusions:

In patients with a broad spectrum of cardiovascular risk factors, SGLTis substantially improve individual hard clinical outcomes and QoL.

198

项与索格列净相关的新闻（医药）

2025-03-28

·GlobeNewswire-Health Care

Lexicon Pharmaceuticals Announces Exclusive License Agreement with Novo Nordisk for LX9851

Lexicon eligible to receive up to $1 billion in upfront and development, regulatory and sales milestone payments, including $75 million in upfront and near-term milestone paymentsTHE WOODLANDS, Texas, March 28, 2025 (GLOBE NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced that it has entered into an exclusive license agreement with Novo Nordisk A/S for LX9851, a first-in-class, oral non-incretin development candidate in obesity and associated metabolic disorders. Under the terms of the agreement, Novo Nordisk obtains an exclusive, worldwide license to develop, manufacture and commercialize LX9851 in all indications. Lexicon will be responsible for completing agreed upon Investigational New Drug (IND) application-enabling activities for LX9851. Novo Nordisk will be responsible for filing the IND, all further development, manufacturing and commercialization of LX9851. Lexicon is eligible to receive upfront and near-term milestone payments of up to $75 million. In total, Lexicon will be eligible to receive $1 billion in upfront and potential development, regulatory and sales milestone payments. Lexicon is also entitled to tiered royalties on net sales of LX9851. LX9851, discovered and developed by Lexicon, is a potent and selective oral small molecule inhibitor of Acyl-CoA Synthetase 5 (ACSL5). ACSL5 plays a key role in the metabolic pathway which regulates fat accumulation and energy balance. Additionally, LX9851 may activate the ileal brake mechanism leading to increased satiety by delaying gastric emptying and suppressing appetite. Preclinical in vivo efficacy data presented at Obesity Week 2024 show that LX9851, when combined with semaglutide, significantly reduced weight, food intake and fat mass compared to semaglutide alone. Separately, LX9851 mitigated weight regain and had positive effects on liver steatosis when introduced after semaglutide discontinuation. "We are thrilled that Novo Nordisk, a global leader in diabetes care and obesity management, has recognized the potential of LX9851," said Mike Exton, Ph.D., chief executive officer and director of Lexicon. "This arrangement decisively strengthens our financial position, providing optionality as we further invest and accelerate our R&D portfolio.” “Novo Nordisk is committed to serving the diverse needs of people living with obesity and other metabolic diseases and to build a pipeline of differentiated drug candidates in this space,” Jacob Sten Petersen, Senior Vice President, Diabetes, Obesity and MASH therapeutic area at Novo Nordisk. “We are pleased to enter this agreement with Lexicon as it will allow us to explore a novel biology and potential treatment paradigm further, and we look forward to building on the great work Lexicon has already done with the development of LX9851.” About LX9851LX9851 is an orally delivered small molecule drug candidate for the treatment of obesity and associated cardiometabolic disorders. Lexicon is investigating the pharmacology of LX9851 as a stand-alone therapy and in combination with GLP-1 agonists such as semaglutide. Lexicon scientists identified the function of ACSL5, the target of LX9851, based on their discovery that knockout mice lacking the target enzyme exhibited favorable phenotypes across multiple measures of metabolic syndrome in preclinical models, including resistance to diet-induced obesity and improved body composition. About Lexicon PharmaceuticalsLexicon is a biopharmaceutical company with a mission of pioneering medicines that transform patients’ lives. Through the Genome5000™ program, Lexicon’s unique genomics target discovery platform, Lexicon scientists studied the role and function of nearly 5,000 genes and identified more than 100 protein targets with significant therapeutic potential in a range of diseases. Through the precise targeting of these proteins, Lexicon is pioneering the discovery and development of innovative medicines to treat disease safely and effectively. Lexicon has a pipeline of promising drug candidates in discovery and clinical and preclinical development in cardiology, neuropathic pain, metabolism and other indications. For additional information, please visit www.lexpharma.com. 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. Safe Harbor Statement This press release contains “forward-looking statements,” including statements relating to Lexicon’s financial position and long-term outlook on its business, growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management’s current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including Lexicon’s ability to meet its capital requirements, conduct preclinical and clinical development and obtain necessary regulatory approvals of pilavapadin (LX9211), LX9851, sotagliflozin and its other drug candidates on its anticipated timelines, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug candidates. Any of these risks, uncertainties and other factors may cause Lexicon’s actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2024 and other subsequent disclosure documents filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise. For Investor and Media Inquiries:Lisa DeFrancesco Lexicon Pharmaceuticals, Inc.lexinvest@lexpharma.com

引进/卖出

2025-03-11

·医学新视点

专家对话：降脂、降糖、减重等药物，如何改善心血管代谢健康？

高血压、血脂异常和肥胖是现代生活中常见的慢性疾病，它们不仅相互关联，还常常共同导致心血管疾病等严重健康问题。密西根大学Eugene Chen（陈育庆）教授与中南大学湘雅二医院彭道泉教授、上海交通大学附属瑞金医院王继光教授为我们分享了关于心血管代谢疾病的最新研究成果与临床治疗进展，并深入探讨了代谢综合征、心血管疾病的风险管理以及最新药物在血脂、血糖、肥胖等方面的应用。陈育庆教授：代谢与心血管健康密不可分陈育庆教授详细探讨了代谢综合征的概念以及其对心血管健康的影响：代谢综合征是一组与肥胖、糖尿病、高血压等疾病相关的病理状态，通常会导致心血管疾病的高发。尤其在中国，心血管代谢疾病的流行情况严峻，据统计，高血压、糖尿病和肥胖分别影响着2.45亿、1.09亿和1.72亿中国人口，而高血压前期、糖尿病前期和超重人群也呈现出更为严重的增长趋势。胰岛素抵抗被认为是多种心血管危险因素的关键驱动因素，它在肥胖、糖尿病和高血压等疾病的发生和发展中起着核心作用。过氧化物酶体增殖物激活受体γ（PPAR-γ）的激活通过控制脂肪、糖类、能量的代谢在疾病的发生中发挥着核心作用，尤其在肥胖和糖尿病患者中影响显著。1997年首次发现的PPAR-γ激动剂[如曲格列酮（troglitazone）、吡格列酮（pioglitazone）和罗格列酮（rosiglitazone）]都成为研究和治疗这些疾病的重要药物。然而，这些药物也有副不良作用，如可能出现体重增加、水潴留、浮肿及肝毒性等。近年来针对糖尿病及心血管疾病的药物研发不断取得进展，钠-葡萄糖共转运体1/2 (SGLT1/2）抑制剂（如sotagliflozin）因其显著的临床效果和低不良反应，成为了治疗糖尿病及心衰患者的热点药物。多项临床试验证明该药物能够降低心血管死亡率，并且对心脏功能恢复具有积极作用。通过全新的药物治疗方法可以同时改善心血管和代谢健康，这一发现进一步认识了心血管疾病与代谢疾病之间的关系，并为临床治疗提供了新的方向。在胰岛素抵抗、高血压、血脂紊乱与肥胖的综合管理中，药物与生活方式干预的结合尤为重要。通过使用新的药物[如胰高血糖素样肽-1（GLP-1）受体激动剂、SGLT2抑制剂、前蛋白转化酶枯草溶菌素9（PCSK9）抑制剂等]并结合健康饮食和适当的运动，能够更有效地控制血脂、血压和胰岛素抵抗，更有助于提高心血管疾病的预防和治疗效果，改善患者的整体健康状况。陈育庆教授特别提到，良好的生活习惯对于心血管健康至关重要，尤其是在控制代谢性疾病方面。通过遵循“Life’s Essential 8”这一健康生活指南，可以显著改善心血管健康。这包括保持充足的睡眠（每天7~9小时）、健康饮食、定期的中等强度运动（每周150分钟），不吸烟，保持健康体重，控制血压、胆固醇水平以及空腹血糖。王继光教授：高血压分期、分级、分型管理的理论与实践在此次讲座中，王继光教授探讨了高血压的防治与管理，强调了早期干预和个体化治疗的重要性。王继光教授表示，通过精确的血压监测与药物调控，结合生活方式的改善，可以有效降低高血压患者的心血管事件风险。近年来，老龄患者尤其是60岁以上人群的高血压患病率显著上升，从2012年的44.6%增至55.7%。王继光教授指出，高血压的管理应该重视分级、分期和分型。分级诊断根据患者的血压水平，分期根据血压对血管和器官的影响来评估，而分型则结合高血压的病因和病理学特征，为患者提供个体化的治疗方案。其次，动态血压监测推动了智能化高血压诊疗中心的建设，提高了血压测量的准确性，支持了个体化治疗的实施。尤其是家庭血压监测的普及，极大地改善了患者自我管理血压的能力，确保了治疗方案的及时调整。此外，王继光教授还深入分析了高血压与肾脏疾病、阻塞性睡眠呼吸暂停综合征（OSAS）等病症的关系，展示了高血压与其他疾病的共性临床表现，尤其是与肾脏疾病的交叉影响。其团队的研究也涉及到高血压患者合并OSAS的治疗，通过持续气道正压（CPAP）治疗，进一步探讨了如何通过改善睡眠呼吸状况来降低高血压患者的心血管风险，为综合治疗提供了新的视角和依据。随着新型药物的不断涌现，王继光教授展示了药物如baxdrostato和沙库巴曲缬沙坦/阿利沙坦在临床试验中的降压效果，特别是在长期管理高血压中的优势。通过对比不同的药物治疗方案，王继光教授强调，当前降压治疗所取得的巨大进步及其潜在的广阔前景。这些新型药物不仅为高血压的治疗提供了更多选择，还可能改善患者的长期预后。通过逐步提高治疗率和达标率，高血压的控制率有望达到50%，这一目标的实现，将为中国心血管疾病的防治奠定坚实的基础。彭道泉教授：血脂剩余风险治疗进展在本次讲座中，彭道泉教授深入探讨了血脂剩余风险的识别与治疗策略，重点介绍如何利用最新的药物和治疗方法进一步减少动脉粥样硬化性心血管疾病（ASCVD）风险。彭道泉教授指出，尽管常规降脂治疗可以有效降低低密度脂蛋白胆固醇（LDL-C），但仍有部分患者存在血脂剩余风险，表现为甘油三酯（TG）、高密度脂蛋白（HDL）及其他脂质异常。为此，他强调了分层治疗的重要性，通过评估LDL-C、TG、脂蛋白（a）等指标，判断是否需要使用新型药物，如PCSK9抑制剂，这种精准的治疗方法有助于更有效地管理血脂异常。接着，彭道泉教授详细介绍了bempedoic酸的作用机制。Bempedoic酸可以通过抑制肝脏的ATP柠檬酸裂解酶（ACL）降低胆固醇合成，从而显著降低LDL-C水平。研究显示，bempedoic酸在临床应用中效果显著，尤其是在60个月的追踪中，LDL-C水平持续降低，心血管事件的发生率也有所减少。另外，bempedoic酸对心血管事件的预防同样有效果，特别是在不耐受他汀类药物的患者中，这些研究结果为bempedoic酸的临床应用提供了重要依据。近几年涌现的几种新型药物，如zodasiran和plozasiran，在临床试验中也表现出了良好的疗效。Zodasiran通过RNA干扰降低TG，最大降低幅度为63%，非高密度脂蛋白胆固醇（non-HDL-C）也减少了36%，载脂蛋白B（ApoB）下降了22%。Plozasiran则在24周的研究中显著减少了TG（62.4%）及ApoB（20%）。这些结果表明，这些新药在治疗高脂血症方面具有巨大的潜力。此外，还有ApoCIII抑制剂可以通过降低TG及apoB水平，在改善相关脂质代谢紊乱中表现出积极的作用，为患者提供了进一步的治疗选项。在治疗过程中，患者的脂质水平变化明显，且未见显著副作用。随着新药的不断推出，siRNA技术也开始在脂质代谢领域展现其强大的潜力。通过干扰特定的基因表达，这些小分子药物能够直接影响脂质的合成与代谢，为高脂血症的治疗提供了新的方向，尤其是在提高高密度脂蛋白（HDL）功能方面表现突出。总的来说，这些新型降脂药物的出现，为高脂血症患者提供了更多的治疗选择，且具有显著的疗效和良好的安全性。这些药物不仅能有效降低血脂，还能进一步降低心血管疾病的风险，为患者带来更好的生活质量。随着研究的深入，未来这些药物的临床应用将更加广泛，进一步推动心血管疾病治疗的进步。相关阅读 3年持续降脂，预防心血管疾病！JAMA子刊：无需高强度他汀，替代方案安全有效降脂至少80%，1年多内持续降低！JAMA：RNAi疗法为心血管疾病患者带来新希望预防心血管疾病，健康老年人停用阿司匹林安全吗？重磅研究带来启示中国人群新证据：无论高血压病史长短，达到<130 mmHg就能降低心血管疾病风险！挑战认知？没接受治疗，42%患者血压恢复正常，心血管疾病风险还降低34%！欢迎投稿：学术成果、前沿进展、临床干货等主题均可，点此了解投稿详情。参考资料（可上下滑动查看） [1]Saklayen MG. The Global Epidemic of the Metabolic Syndrome. Curr Hypertens Rep. 2018;20(2):12. Published 2018 Feb 26. doi:10.1007/s11906-018-0812-z [2]国家心血管病中心阜外医院鲁向锋教授 [3]Li Y, Zhou D, Ren Y, et al. Mir223 restrains autophagy and promotes CNS inflammation by targeting ATG16L1. Autophagy. 2019;15(3):478-492. doi:10.1080/15548627.2018.1522467 [4]Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes [published correction appears in N Engl J Med. 2007 Jul 5;357(1):100.]. N Engl J Med. 2007;356(24):2457-2471. doi:10.1056/NEJMoa072761 [5]王继光.内科理论与实践.2014;9(6):365-368. [6]王继光.高血压数字平台与数字疗法.临床心血管病杂志,2022;38(8):606-609. [7]Wang JG. Annals of Translational Medicine 2018; 6(15):296. [8]Writing Committee, Lloyd-Jones DM, Morris PB, et al. 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Solution Set Oversight Committee [published correction appears in J Am Coll Cardiol. 2023 Jan 3;81(1):104. doi: 10.1016/j.jacc.2022.11.016.]. J Am Coll Cardiol. 2022;80(14):1366-1418. doi:10.1016/j.jacc.2022.07.006 [9]Terlizzi M, Bossi A. ProtecT trial: What's new after 15 years of follow-up: Re: Hamdy FC and colleagues; N Engl J Med. 2023 Apr 27. Urologia. 2024;91(1):3-4. doi:10.1177/03915603231225604 [10]Teo YH, Chia AZQ, Teo YN, et al. The impact of sodium-glucose cotransporter inhibitors on blood pressure: a meta-analysis and metaregression of 111 randomized-controlled trials. J Hypertens. 2022;40(12):2353-2372. doi:10.1097/HJH.0000000000003280 [11]Stroes ESG, Alexander VJ, Karwatowska-Prokopczuk E, et al. Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome. N Engl J Med. 2024;390(19):1781-1792. doi:10.1056/NEJMoa2400201 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。分享，点赞，在看，传递医学新知

2025-03-11

·化学经纬

索格列净的合成研究路线汇总

索格列净(1) 的化学结构包含5 个连续手性中心的糖基部分、1 个芳基疏水片段和1 个甲硫醚基团。通过逆合成分析可知，1 的合成有3 个重点：①手性中心的构建；②芳基片段与糖基的连接；③甲硫基的引入。对1 的合成路线进行总结，归纳了以L- 木糖为起始原料的5 条合成路线、以L- 葡萄糖为起始原料的1 条合成路线和以达格列净乙酸酯为起始原料的1 条路线。合成路线一：合成路线二：合成路线三：合成路线四：合成路线五：合成路线六：合成路线七：本文总结了7条合成路线，路线一至路线五均以L-木糖为起始原料，其中路线一是醛直接与芳基片段偶联，路线二至路线五是得到L-木糖Weinreb酰胺的替代体吗啉酰胺后，与芳基片段偶联，再引入甲硫醚片段，其中路线二是1的原研工艺路线。路线六虽是以L-葡萄糖为起始原料，实则与路线二相似,也是先得到吗啉酰胺,再与芳基片段偶联。路线七是一种全新的方法，但是否可以放大生产有待进一步验证。 1合成的最优策略为糖环部分根据构型选择L-木糖作为原料，芳环片段与糖环的偶联采用格氏试剂与吗啉酰胺偶联，甲硫基的引入采用先硫脲试剂硫代、再甲基化的方法。3位羟基是否需要保护，有待商榷。随着1的专利保护期到期时间的临近，相信会出现更多高效、绿色的合成路线报道。

专利到期

100 项与索格列净相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10669	索格列净	A10BK06	DB12713

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
心脏衰竭	美国	Lexicon Pharmaceuticals, Inc.	2023-05-26
1型糖尿病	欧盟	NCI Healthcare LLC	2019-04-26
1型糖尿病	冰岛	NCI Healthcare LLC	2019-04-26
1型糖尿病	列支敦士登	NCI Healthcare LLC	2019-04-26
1型糖尿病	挪威	NCI Healthcare LLC	2019-04-26

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
慢性肾病	申请上市	美国	Lexicon Pharmaceuticals, Inc.	2024-06-21
非梗阻性肥厚型心肌病	临床3期	美国	Lexicon Pharmaceuticals, Inc.	2024-09-24
非梗阻性肥厚型心肌病	临床3期	阿根廷	Lexicon Pharmaceuticals, Inc.	2024-09-24
非梗阻性肥厚型心肌病	临床3期	英国	Lexicon Pharmaceuticals, Inc.	2024-09-24
梗阻性肥厚型心肌病	临床3期	美国	Lexicon Pharmaceuticals, Inc.	2024-09-24
梗阻性肥厚型心肌病	临床3期	阿根廷	Lexicon Pharmaceuticals, Inc.	2024-09-24
梗阻性肥厚型心肌病	临床3期	英国	Lexicon Pharmaceuticals, Inc.	2024-09-24
2型糖尿病	临床3期	美国	Lexicon Pharmaceuticals, Inc.	2016-11-01
2型糖尿病	临床3期	美国	Sanofi	2016-11-01
2型糖尿病	临床3期	加拿大	Sanofi	2016-11-01

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03315143 (SCORED, Lancet) 人工标引	临床3期	缺血	10,584	Sotagliflozin	窪鏇獵觸淵繭夢簾遞顧(壓遞醖壓範鹽顧糧襯糧) = 膚範夢艱鏇顧獵鹹範遞醖艱糧糧夢窪築顧夢遞 (願衊觸憲醖製襯窪鹽範 ) 更多	积极	2025-02-14
				Placebo	窪鏇獵觸淵繭夢簾遞顧(壓遞醖壓範鹽顧糧襯糧) = 鏇製選壓簾鹹遞遞網襯醖艱糧糧夢窪築顧夢遞 (願衊觸憲醖製襯窪鹽範 ) 更多
NCT02531035 \| NCT02384941 \| NCT02421510 (Pubmed) 人工标引	N/A	1型糖尿病 \| 慢性肾病	-	Sotagliflozin 200mg (CKD)	鹽窪窪膚憲簾廠積築選(齋顧鏇網遞顧襯夢繭範) = 繭淵憲範獵鹹鏇艱衊鏇鑰夢餘廠壓艱遞壓壓壓 (鹹範遞艱獵糧願願憲繭 ) 更多	积极	2024-11-01
				Sotagliflozin 400mg (CKD)	鹽窪窪膚憲簾廠積築選(齋顧鏇網遞顧襯夢繭範) = 獵膚鏇壓糧顧蓋淵製遞鑰夢餘廠壓艱遞壓壓壓 (鹹範遞艱獵糧願願憲繭 ) 更多
NCT03285594 (SOTA-INS, GlobeNewswire) 人工标引	临床3期	2型糖尿病	-	Sotagliflozin 400 mg	積簾選醖夢醖範餘淵艱(餘鬱襯選願鬱廠願膚糧) = 顧醖壓襯憲鹽膚憲鹹壓築積鏇醖範窪鹹醖醖構 (餘鑰觸憲餘齋膚鏇醖糧 )	积极	2024-09-10
				Sotagliflozin 200 mg	積簾選醖夢醖範餘淵艱(餘鬱襯選願鬱廠願膚糧) = 膚夢鑰壓膚築觸鹹衊壓築積鏇醖範窪鹹醖醖構 (餘鑰觸憲餘齋膚鏇醖糧 )
NCT03521934 (SOLOIST-WHF, Pubmed \| J Am Coll Cardiol)	临床3期	2型糖尿病 \| 心脏衰竭	-	Sotagliflozin	觸製鏇艱製鑰鬱淵膚廠(淵壓蓋顧鏇糧壓遞觸夢) = The baseline KCCQ-12 score was low overall (median: 41.7; Q1-Q3: 27.1-58.3) and improved by 4 months in both groups 獵鬱構構鏇製鹽獵顧淵 (鏇醖鏇簾憲構膚簾構願 )	积极	2024-09-01
				Placebo
ESC2024	N/A	糖尿病	-	Sotagliflozin	選艱鑰膚構憲齋膚餘願(鬱窪壓繭廠簾構鏇窪糧) = 餘膚範衊膚積夢製構膚艱簾鹹遞醖窪製窪願構 (艱積鑰範積遞膚壓鏇積 ) 更多	-	2024-08-30
				Placebo	選艱鑰膚構憲齋膚餘願(鬱窪壓繭廠簾構鏇窪糧) = 觸鏇襯鬱簾鏇獵簾顧鏇艱簾鹹遞醖窪製窪願構 (艱積鑰範積遞膚壓鏇積 ) 更多
924-P (ADA2024)	临床3期	2型糖尿病追加	570	Sotagliflozin 400 mg	蓋願鏇夢選鬱壓廠積壓(廠顧觸餘餘網鏇構憲壓) = 衊夢蓋餘齋艱顧觸糧構膚鹹醖選蓋構觸獵築廠 (願構簾選憲淵壓艱壓鑰 )	积极	2024-06-14
				Sotagliflozin 200 mg	蓋願鏇夢選鬱壓廠積壓(廠顧觸餘餘網鏇構憲壓) = 鬱簾淵衊積積築膚範憲膚鹹醖選蓋構觸獵築廠 (願構簾選憲淵壓艱壓鑰 )
917-P (ADA2024)	临床3期	2型糖尿病	770	Sotagliflozin 400 mg	醖蓋齋夢獵艱遞鑰願鬱(觸繭願蓋衊夢鏇鑰廠蓋) = Other adverse events in the SOTA group aligned with expectations associated with SGLTi therapy 廠簾蓋觸願醖顧蓋廠膚 (廠顧鹹齋醖餘範觸憲範 ) 更多	积极	2024-06-14
				Empagliflozin 25 mg
NCT03315143 (SCORED, GlobeNewswire) 人工标引	临床3期	心脏衰竭	1,932	INPEFA® (sotagliflozin)	願築築顧鑰窪鏇顧鹹壓(顧遞憲糧遞遞醖襯窪築) = 網鑰簾蓋夢蓋壓積膚獵壓醖衊鑰鏇憲觸糧鏇鹽 (窪淵積窪鑰網積願廠構 )	积极	2024-05-14
SOLOIST-WHF and SCORED (ESC2024)	N/A	obesity \| type 2 diabetes (T2D)	-	Sotagliflozin	憲願齋餘範獵夢簾獵鹽(蓋積夢積鑰窪憲顧築蓋) = 鏇鏇觸網蓋繭積憲蓋顧艱簾構觸艱醖鏇艱襯襯 (鏇蓋糧醖齋願願膚遞壓 )	积极	2024-05-14
NCT03315143 (SCORED, ACC2024) 人工标引	临床3期	心血管疾病 \| 2型糖尿病 \| 慢性肾病	10,584	Sotagliflozin	鬱積蓋鬱構壓積艱鬱艱(鑰齋網蓋鹽網築襯鏇簾) = 願鹹積繭蓋鏇網襯淵鏇窪鬱範繭艱糧鏇構醖艱 (窪窪築選願艱鏇鑰壓鏇 ) 更多	积极	2024-03-25
				Placebo	鬱積蓋鬱構壓積艱鬱艱(鑰齋網蓋鹽網築襯鏇簾) = 鬱襯壓憲鏇獵齋選鹽夢窪鬱範繭艱糧鏇構醖艱 (窪窪築選願艱鏇鑰壓鏇 ) 更多