更新于：2024-06-29

Pioglitazone Hydrochloride

盐酸吡格列酮

更新于：2024-06-29

概要

概要

基本信息

药物类型

小分子化药

别名

(±)-5-((4-(2-(5-ethyl-2-pyridinyl)ethoxy)phenyl)methyl)-2,4-thiazolidinedione、5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione、pioglitazone

+ [32]

靶点

PPARγ

作用机制

PPARγ激动剂(过氧化物酶体增长因子活化受体γ激动剂)

治疗领域

内分泌与代谢疾病

在研适应症

2型糖尿病

非在研适应症

阿尔茨海默症心血管疾病冠心病+ [14]

原研机构

Takeda Pharmaceutical Co., Ltd.

在研机构

Takeda Pharmaceuticals U.S.A., Inc.Actavis Group PTC ehf.Accord Healthcare SLU

+ [3]

非在研机构

KRKA ddTeva Pharmaceuticals Europe BV

Strekin AG初创企业

+ [3]

最高研发阶段批准上市

首次获批日期

美国 (1999-07-15),

2型糖尿病

最高研发阶段(中国)批准上市

特殊审评孤儿药 (美国)、孤儿药 (欧盟)

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结构

分子式C19H21ClN2O3S

InChIKeyGHUUBYQTCDQWRA-UHFFFAOYSA-N

CAS号112529-15-4

关联

466

项与盐酸吡格列酮相关的临床试验

NCT06246799 / Not yet recruiting临床3期IIT

Comparative Effectiveness of Two Initial Combination Therapies in Patients With New Onset Diabetes

The goal of this randomized, open labelled clinical trial is to examine the efficacy, durability, and mechanism of HbA1c reduction produced by the combination of pioglitazone plus tirzepatide versus metformin plus sitagliptin in recently diagnosed type 2 diabetes mellitus patients.
The main question[s] it aims to answer are:
How effective is the combination of pioglitazone plus tirzepatide in managing blood sugar levels in people with type 2 diabetes? How does this combination compare to the use of metformin plus sitagliptin in controlling blood sugar levels? Participants will receive Pioglitazone beginning at 15 mg daily and ending 45 mg daily. (15mg month 1, 30mg month 2 and 45mg at month 3 onwards)

开始日期2024-07-01

申办/合作机构

University of Texas Health Science Center At San Antonio

[+1]

NCT06446531 / Recruiting临床1期IIT

Pioneering and Affordable Strategies to Prevent Progression of Prediabetes, Obesity and CV Risk in Hispanics

The investigators are studying how to help people with prediabetes (Pre-DM) and obesity. The goal is to use new and affordable treatments to bring blood sugar levels back to normal and help participants to lose weight. The investigators also want to reduce participants risk of heart problems. The study team will look at how these treatments affect metabolism and other body functions to help find new ways to treat diabetes and obesity in the future.

开始日期2024-07-01

申办/合作机构

University of Texas Health Science Center At San Antonio

NCT05727761 / Not yet recruiting临床2期IIT

Pioglitazone-Metformin Combination Treatment for High Risk Oral Preneoplasia

This is a Phase IIa oral cavity leukoplakia study of pioglitazone 15mg and metformin 500mg BID for 12 weeks. The primary objective is to determine the clinical and histologic changes of leukoplakia from baseline following a 12 week course of twice daily pioglitazone-metformin. Outcomes are defined as are a reduction of the leukoplakia grade in > 50% of treated participants and a partial or complete clinical response defined as 50% or greater reduction in the sum of measured targeted lesions. In addition, participants who show clinical and histologic improvement should correlate with a significant reduction of Ki-67 proliferative indices in lesions of these participants as compared to baseline.

开始日期2024-06-15

申办/合作机构

University of Minnesota

100 项与盐酸吡格列酮相关的临床结果

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100 项与盐酸吡格列酮相关的转化医学

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100 项与盐酸吡格列酮相关的专利（医药）

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6,041

项与盐酸吡格列酮相关的文献（医药）

2024-03-01·Research in veterinary science

The effect of peroxisome proliferator-activated receptor gamma (PPARγ) as a mediator of dietary fatty acids and thiazolidinedione in pulmonary arterial hypertension induced by cold stress of broilers

Article

作者: Masoudi, Ali Akbar ; Grimes, Jesse L ; Rahimi, Mahsa ; Sharafi, Mohsen ; Rahimi, Shaban ; Karimi Torshizi, Mohammad Amir

The objective of this experiment was to evaluate the effects of dietary fish oil and pioglitazone as peroxisome proliferators-activated receptor gamma (PPARγ) activating ligands on the reduction of cold-induced ascites in broiler chickens. A total of 480 one-day-old (Ross 308) male chicks were randomly allocated to four treatment groups with eight replicates of 15 birds each. The following treatments were used: 1) ambient temperature (negative control), with basal diet; 2) cold-induced ascites (positive control), with basal diet; 3) cold-induced ascites, with basal diet +10 mg/kg/day pioglitazone and 4) cold-induced ascites, with basal diet +1% of fish oil. When compared with the positive control, body weight gain was higher (P ≤ 0.05) for broilers fed diets containing fish oil and pioglitazone at 28, 42, and 0-42 d. Broilers under cold-induced ascites had the highest blood pressure at 21 and 42 d, while fish oil and pioglitazone treatment reduced the blood pressure (P ≤ 0.05). Red blood cells, white blood cells, hematocrit, erythrocyte osmotic fragility, bursa of Fabricius and spleen weights were improved (P ≤ 0.05) for chickens fed fish oil diets and pioglitazone compared to the cold-induced ascites (positive control). Exposure to cold temperature resulted in an increase in plasma T₃ and T₃/T₄ ratio and decline in plasma T₄ (P ≤ 0.05). In conclusion, PPARγ agonist pioglitazone and fish oil as source of omega-3 polyunsaturated fatty acid could be used as a strategy to reduce the negative effects of pulmonary arterial hypertension and ascites in broiler chickens.

2024-03-01·Molecular and cellular endocrinology

Canagliflozin improves fatty acid oxidation and ferroptosis of renal tubular epithelial cells via FOXA1-CPT1A axis in diabetic kidney disease

Article

作者: Fan, Xunjie ; Wang, Qingzhu ; Song, Yi ; Wang, Shanshan ; Chen, Duo ; Gan, Tian ; Shao, Mingwei ; Zhang, Wei ; Guo, Feng ; Qin, Guijun ; Luo, Yuanyuan ; Wei, Fangyi ; Zhao, Yanyan

Impaired fatty acid oxidation (FAO) is a metabolic hallmark of renal tubular epithelial cells (RTECs) under diabetic conditions. Disturbed FAO may promote cellular oxidative stress and insufficient energy production, leading to ferroptosis subsequently. Canagliflozin, an effective anti-hyperglycemic drug, may exert potential reno-protective effects by upregulating FAO and inhibiting ferroptosis in RTECs. However, the mechanisms involved remain unclear. The present study is aimed to characterize the detailed mechanisms underlying the impact of canagliflozin on FAO and ferroptosis. Type 2 diabetic db/db mice were administrated daily by gavage with canagliflozin (20 mg/kg/day, 40 mg/kg/day) or positive control drug pioglitazone (10 mg/kg/day) for 12 weeks. The results showed canagliflozin effectively improved renal function and structure, reduced lipid droplet accumulation, enhanced FAO with increased ATP contents and CPT1A expression, a rate-limiting enzyme of FAO, and relieved ferroptosis in diabetic mice. Moreover, overexpression of FOXA1, a transcription factor related with lipid metabolism, was observed to upregulate the level of CPT1A, and further alleviated ferroptosis in high glucose cultured HK-2 cells. Whereas FOXA1 knockdown had the opposite effect. Mechanistically, chromatin immunoprecipitation assay and dual-luciferase reporter gene assay results demonstrated that FOXA1 transcriptionally promoted the expression of CPT1A through a sis-inducible element located in the promoter region of the protein. In conclusion, these data suggest that canagliflozin improves FAO and attenuates ferroptosis of RTECs via FOXA1-CPT1A axis in diabetic kidney disease.

2024-03-01·Therapie

Drug-induced tumoral disease: A global pharmacovigilance database analysis

Article

作者: Despas, Fabien ; Zelmat, Yoann

INTRODUCTION:

Cancer remains a worldwide threat, having caused almost 10 million deaths in 2020. The American Cancer Society has identified both known and probable carcinogens, including commonly used drugs. The aim of this study is to describe the drugs most frequently reported in the occurrence of cancer.

METHODS:

Among all individual case safety reports (ICSRs) in the global pharmacovigilance database VigiBase, we searched for the 50 most reported drugs with an adverse drug reaction term belonging to the query "Malignant or unspecified tumors" until June 30, 2023. Then, we extracted the disproportionality measurement data, information component (IC), and reporting odds ratio (ROR) in order to assess a disproportionality signal.

RESULTS:

Among all ICSRs in VigiBase, 871,925 contained an ADR belonging to the SMQ "Malignant or unspecified tumors". Ranitidine was the drug with the most reported ADRs related to cancer (n=106,484), followed by lenalidomide (n=13,466), and etanercept (n=8014). The drugs with the highest IC were ranitidine (IC=5.2, 95% confidence interval [95% CI]=5.2-5.2), pioglitazone (1353 ICSRs, IC=4.2, 95% CI=4.2-4.2), and regorafenib (1272 ICSRs, IC=2.8, 95% CI=2.8-2.8).

DISCUSSION:

Our results show that the main pharmacological mechanisms are associated with ranitidine (link with levels of N-nitrosodimethylamine in ranitidine-based drugs), gene-activating drugs (pioglitazone: link with agonist effects on PPAR-γ gene activation), various pharmacological families with immunosuppressive effects (protein kinase inhibitors, immunomodulators, azathioprine, etc.), certain types of protein kinase inhibitors whose oncogenic mechanisms remain unclear (regorafenib, sorafenib, imatinib, ibrutinib, etc.), and hormone antagonists (tamoxifen, letrozole). Special monitoring of patients exposed to these drugs may be required. Further studies are needed to assess the risk with certain drugs in this ranking.

项与盐酸吡格列酮相关的新闻（医药）

2024-06-25

·药渡

武田制药药物交易风云：近年数据透视其战略布局新动向

来源：药渡撰文：天际微步编辑：哦呼武田制药（武田药品工业株式会社，Takeda）是一家位于日本东京的老牌药企，从中草药销售起步已经拥有243年历史，如今已成为亚洲最大的制药公司，在全球MNC药企中排名TOP20之列。2023财年武田制药的营收为4.26万亿日元，同比增长5.9%，在全球药企中的排名为第13位。与强生、辉瑞等其他大MNC有较强自研能力不同，武田制药从药物销售贸易起步，积攒了原始资本，后在仿制美国药上布局，凭借四大me too品种（亮丙瑞林微球、兰索拉唑、坎地沙坦、吡格列酮）崛起。在这过程中虽有布局自主研发管线，但效果不佳，只得不断地并购或者交易来拓展管线，因此武田制药的交易事件相当频繁。从2005年第一次海外收购美国syrrx inc，武田逐渐形成了以肿瘤、消化、罕见病和神经为主，疫苗和血制品为辅的业务版图。从近两年武田的药物交易事件来看一下武田的重点方向和布局策略变化。 2023年以来武田的药物交易事件盘点从2023年初开始武田制药就一直在进行内部调整，以应对重磅产品专利到期（替度鲁肽、利右苯丙胺等）带来的业绩冲击。一方面，砍掉尚未见效的早期管线、收缩战线，据公开资料，2023年武田制药共有包括肺癌产品Exkivity、阿尔茨海默病药物DNL-919等18款药物从管线中剔除，还终止了与JCR制药公司的AAV基因治疗，与Noile-Immune的新一代实体瘤CAR-T疗法等的项目合作。在其362个药物管线中，135个已经处于终止状态。图1.武田制药的管线进展情况（来源：药渡数据）但另一方面，武田仍继续购进具有上市潜力的管线来形成新增长力。据不完全统计，2023年至2024年6月份，武田制药产生的药物交易有12笔。表1.2023年以来武田制药的药物交易事件（来源：药渡数据及公开资料整理） 2024年6月14日，武田制药引进亚盛医药的奥雷巴替尼，用于治疗慢性髓性白血病（CML），获得其中国以外的商业化权利。此前，武田已有CML治疗药物泊那替尼，但即将在2026年专利到期，引进奥雷巴替尼可以继续利用此前积累的市场方面优势将新产品大卖，保持在CML治疗领域的领先地位。 2024年5月23日，与上海达歌生物达成独家许可协议，以发现和开发用于肿瘤学、神经科学和炎症领域多个靶点的新型分子胶降解剂。达歌生物将利用其研发平台，针对武田选定的特定疾病靶点，发现、验证和优化分子胶降解剂，在达到一定进展阶段后，这些项目将移交给武田进行进一步开发和商业化。此次主要利用达歌生物的研发创新能力来帮助武田在分子胶降解剂这一类新型药物上进行探索。 2024年5月13日，武田制药引进AC Immune的阿尔茨海默症Aβ疫苗疗法ACI-24.060，阿尔茨海默症也属于武田重点布局的神经性疾病范畴，需要一款重磅新药来塑造竞争力。 2024年4月16日，与Kumquat生物科学达成战略合作和独家全球许可协议，推进新型口服免疫肿瘤药物，武田承担并资助除了由Kumquat主导的1期试验活动之外的所有开发和商业化活动。 2024年1月31日，与Protagonist达成全球许可和合作协议，共同开发罕见血液病药物Rusfertide（其基于多肽的新化学实体），目前正处于关键的 3 期试验，用于治疗真性红细胞增多症。 2023年期间，先后引进和黄医药的用于治疗经治转移性结直肠癌的呋喹替尼， Nimbus Lakshmi的银屑病药物TYK2抑制剂NDI-034858，中国生物制药子公司F-star的肿瘤多特异性抗体免疫疗法，ImmunoGen针对铂耐药卵巢癌的FRα ADC新药ELAHERE，以及AcuraStem的用于治疗肌萎缩性侧索硬化症（ALS）的创新反义寡核苷酸（ASO）疗法AS-202，信念医药治疗B型血友病的AAV基因治疗BBM-H901注射液…… 武田的布局重点和变化？从2023年以来的交易情况看，武田的布局焦点，仍然是围绕其四大核心疾病业务领域，包括肿瘤药物（亚盛医药的奥雷巴替尼、Kumquat合作的肿瘤药物、F-star的肿瘤多特异性抗体、ImmunoGen的FRα ADC新药），偏爱和引进了当下热点的ADC和多抗药物；胃肠道药物（和黄的呋喹替尼），通过引进销量不错的呋喹替尼来延续消化疾病领域的优势；罕见病药物（罕见血液病药物Rusfertide、肌萎缩性侧索硬化症的ASO疗法、血友病的AAV基因治疗）。神经疾病药物（AC Immune的阿尔茨海默症Aβ疫苗）、还有自免疾病（银屑病药物TYK2抑制剂）。从药物类型看，引进新技术、新型疗法如分子胶降解剂、AAV基因疗法、多肽药物分子、ADC等，这些新药物能解决传统药物难以解决的问题，更具明显疗效和价值。总之，武田近两年的布局仍然是主要基于其多年来在肿瘤、胃肠道、罕见病和神经等疾病领域所积累的市场销售优势，引进相应的新产品管线，来延续和保持公司的领先优势。在布局疾病适应症上肿瘤已成为重量板块，相关产品数量最多，这也是因为当下肿瘤仍是需求空间最大的疾病类型。在药物类型上新兴技术的引进也是围绕前述疾病类型，可见武田深耕的决心。编者按：近年来，武田制药通过不断引进新的药物管线和技术，以应对市场挑战，保持公司的领先优势。在疾病领域方面，武田制药始终围绕上述四大核心业务领域进行布局。在技术引进方面，武田制药注重新兴技术和新型疗法的研发与应用。未来，随着科技的不断进步和市场需求的不断变化，武田制药能否继续保持敏锐的市场洞察力和创新能力？药渡将持续关注。 *声明：本文仅是介绍医药疾病领域研究进展或简述研究概况或分享医药相关讯息，并非也不会进行治疗或诊断方案推荐，也不对相关投资构成任何建议。内容如有疏漏，欢迎沟通指出！点击下方“药渡“，关注更多精彩内容 100%预防艾滋！吉利德科学创新药物Lenacapavir 3期临床结果喜人欧洲杯来了！哪些国家最有望夺得“最佳药物管道”奖杯？美国Arthrosi公司创新药AR882溶解痛风石，2期临床试验成果亮相2024欧洲风湿病学大会点击下方关注，聚焦医药创新一手资讯

并购专利到期细胞疗法基因疗法疫苗

2024-06-05

·GlobeNewswire-Health Care

Late Breaking Poster Shows a Novel Oral Insulin Sensitizer Azemiglitazone (MSDC-0602K) Could Substantially Preserve Lean Muscle in Combination with Weight-Loss GLP1s

Azemiglitazone (MSDC-0602K) working through a newly identified mitochondrial target adds cardiometabolic benefit to GLP-1 receptor agonists Benefit includes preservation of lean muscle, which could expand the usefulness of the new class of GLP-1 weight loss drugs Recent paper in press in Hepatology emphasizes the important effect of reducing fasting insulin and posters at ADA in Orlando later in June KALAMAZOO, Mich., June 05, 2024 (GLOBE NEWSWIRE) -- Cirius Therapeutics, a privately-held clinical stage biopharmaceutical company, is presenting new data demonstrating the unique potential of combining their second-generation insulin sensitizer azemiglitazone (MSDC-0602K) with GLP-1 receptor agonists (GLP-1s). Cirius Therapeutics together with the Dr. Kyle McCommis lab of St. Louis University are presenting a late breaking poster at the European Association for the Study of Liver Disease (EASL) annual meeting, June 5-8 in Milan, Italy, that describes how the second generation insulin sensitizer azemiglitazone may address body composition issues caused by GLP-1s. The poster presents both a post-hoc analysis of the 23 patients with biopsy-proven MASH in the 52-week Phase 2B EMMINENCE trial who also had concomitant type 2 diabetes and were already on a stable dose of a GLP-1, and data from a pre-clinical study in diabetic db/db mice with GLP-1 liraglutide. These data show: The addition of any dose of azemiglitazone to patients on a GLP-1 improved all circulating parameters, especially HbA1c and liver histology.In the accompanying preclinical study in diabetic db/db mice: The combination of azemiglitazone and the GLP-1 liraglutide, new body composition measurements demonstrated a significant preservation of lean body mass (or muscle) in the combined presence of azemiglitazone, whereas liraglutide alone decreased lean body mass.Together, the combination also produced a synergistic improvement in glucose tolerance that occurred with less elevation of circulating insulin and an increase in pancreatic insulin content.Azemiglitazone also increased the amount of brown adipose tissue (BAT) alone and in combination with liraglutide. BAT is known for its ability to burn calories and store energy. GLP-1s are highly effective weight loss drugs, but they do not directly affect the underlying insulin resistance, are usually used for finite periods of time, and cause loss of both adipose and lean mass, which may limit their use in certain patient populations. Together these new data suggest this combination could optimize metabolic control and produce healthier weight loss and weight maintenance. Dr. Jerry Colca, Chief Scientific Officer of Cirius Therapeutics, said, “This second-generation insulin sensitizer was designed to take advantage of the newly discovered mitochondrial target of the thiazolidinediones (TZDs), which is the mitochondrial pyruvate carrier (MPC). Azemiglitazone avoids the direct activation of PPAR-γ, which has resulted in a significantly improved safety profile versus the first-generation insulin sensitizers. The aha realization here is that this novel identified mechanism of action of TZDs could provide a differentiated solution to the limitations with GLP-1 receptor agonists. Based on these new preclinical results, azemiglitazone could allow patients to lose fat without having to lose muscle. This finding together with the additive benefit on all other parameters could make azemiglitazone the optimal partner for the GLP-1s.” Dr. Kyle McCommis, Assistant Professor in Biochemistry and Molecular Biology at St. Louis University, said, “Our lab has been interested in the implications of this newly identified MPC target, which sits at the crossroads of regulating metabolism in many cell types. We have only recently recognized the positive effects on skeletal muscle and body composition, and we look forward to more detailed studies into the potential of this newly identified mechanism of action.” EASL Annual Meeting Title: Azemiglitazone in Combination with GLP1 Agonists Increases Benefit and Could Preserve Lean MassLate Breaking Poster LB-10, June 5-9 2024Discussions Late Breaking poster allows for discussions throughout the meetingPresenting author: Jerry R. Colca, PhD Additional New Publication and Posters at American Diabetes Association Meeting in Orlanda, Florida: Harrison SA, Dubourg J, Knott M, Colca J. Hyperinsulinemia, an overlooked clue and potential way forward in metabolic dysfunction-associated steatotic liver disease. Hepatology, online and in press. 2024-1582-P Fasting Insulin as an Independent Predictor of Metabolic Dysfunction–Associated Steatohepatitis (MASH) Severity. Authors: Stephen A. Harrison, Julie Dubourg, Sophie Jeannin, Jerry R. Colca, and Vlad Ratzu.2024-892-P: Potential for New Oral Insulin Sensitizers in Combination with GLP-1 Agonists. Author: Jerry R. Colca About Azemiglitazone Azemiglitazone is a novel once-daily, oral second-generation insulin sensitizer that was designed to exert pharmacology similar to pioglitazone without directly activating the transcription factor PPAR-γ. This allows dosing to full effect on the recently identified mitochondrial target, the mitochondrial pyruvate carrier (MPC), and directly impacts the underlying dysmetabolism of chronic metabolic disease. Azemiglitazone has completed all preclinical studies including 2-year carcinogenicity studies and 7 US clinical trials, including a 52-week dose-ranging study in subjects with MASH with and without type 2 diabetes (and mostly overweight and obese). Phase 3 clinical development will examine the potential of azemiglitazone to fulfill the original promise of insulin sensitizing pharmacology, which is the underlying pathophysiology of chronic metabolic disease. Of particular interest will be the ability to work in combination with weight loss approaches such as the GLP-1s. About Cirius Therapeutics Cirius is a clinical-stage biopharma company focused on the development and commercialization of innovative therapies for the treatment of metabolic diseases. Its lead product candidate, azemiglitazone (MSDC-0602K), is a potential best-in-class small molecule being developed as a once-daily oral therapy, selectively designed to modulate the mitochondrial target MPC, which mediates at the cellular level the effects of overnutrition, a major cause of Type 2 Diabetes, Obesity, MASH, and other metabolic disorders. Contacts: Jerry R. Colca, PhD; jcolca@ciriustx.comMina Sooch, MBA, msooch@ciriustx.com Forward looking Statements: This press release contains "forward-looking statements" within the meaning of the federal securities laws. These forward looking statements are not facts, but rather are based on current expectations. Forward-looking statements can be identified by words such as: "could", "believe," "project," and similar references to future results. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements.

临床2期临床3期临床结果

2024-06-05

·药时代

降糖药研发去向何方？

错过了「星起点」宣讲会？问答实录拿走不谢～正文共： 3885字 11图预计阅读时间： 10分钟国际糖尿病联盟(IDF)发布的《2021全球糖尿病地图》显示，我国已成为全球糖尿病患者最多的国家，中国糖尿病患病人数已经达到1.4亿，且增长速度逐年递增。巨大的临床需求需要更有效的治疗措施，大批企业围绕血糖控制热门靶点展开研究。GLP-1RA无疑是当前最热门的靶点之一。降糖药研发如何避免因靶点集中带来的内卷？第二届中国糖尿病和代谢性疾病药物器械创新研发大会上，中国医药创新促进会糖尿病与代谢性疾病药物临床研究专业委员会主任委员、北京大学人民医院内分泌科主任纪立农从CKM（心血管-肾脏-代谢三联症）入手，结合临床需求，带来新药研发启示。 CKM齐发，驱动研发需求糖尿病、CVD和CKD是全球范围内威胁人类健康的三大慢性疾病。IDF数据显示，2021年全球20-79岁糖尿病患者数量已达约5亿。2018年全球疾病负担（GBD）研究显示，2017年全球心力衰竭患者约6400万。而2020年GBD研究则指出，同年全球CKD患者约为7亿。当前我国心血管疾病的患病人数达3.3亿，慢性肾脏病患病人群1.2亿，糖尿病患病人群1.41亿，是不可忽视的三大慢病。流行病学研究显示，糖尿病、心血管疾病和慢性肾病之间存在诸多交互联系。患者在发现其中一种疾病后，应引起对其他疾病的重视和预防。数据显示，患有心血管疾病的患者，出现慢性肾病的概率较普通人增加了2倍；有慢性肾病的患者，出现慢性心血管疾病的风险也增加了20%-40%。同时，患有慢性肾病患者出现血糖代谢紊乱的概率也在明显增高。“根据临床数据库的分析，糖尿病患者最常出现的并发疾病就是心衰和慢性肾病，二者发生的风险和严重程度，远高于我们熟悉的卒中、心梗或是外周动脉病变。”纪立农教授介绍。一项关于美国人群的心脏代谢和肾脏特征的演变（1988-2018年）的研究表明，糖尿病、痴呆症、心血管疾病和慢性肾病已成为多个国家的主要死亡原因，与肥胖、高血压、高血糖等多种危险因素紧密相关。纪立农教授指出，通过上述临床证据可以发现，2型糖尿病、心血管疾病和慢性肾病并非各自独立，三者之间互相影响甚至互为因果。针对这种关联密切的综合征，2023年10月，美国心脏协会提出了CKM（心血管-肾脏-代谢综合征）概念，并将其定义为由肥胖、糖尿病、慢性肾脏疾病和心血管疾病（包括心力衰竭、心房颤动、冠心病、脑卒中和外周动脉疾病）之间病理生理相互作用导致的全身性疾病。CKM的病理生理机制复杂，由肥胖导致的病理生理机制可能促进代谢性疾病、心血管疾病和慢性肾病之间相互作用，导致CKM的恶性循环。在临床治疗中，CKM患者已经有了多种选择，STENO-2的多年随访结果展示了联合干预的可行性。但由于CKM“牵一发而动全身”的病理特性，治疗药物需具有对多靶点同时进行干预的功能。数据显示，目前使用的药物干预手段即使在理想临床试验环境下仍存有44%的剩余风险，更有效的减重、控糖和心肾保护的治疗药物和策略正是临床上未被满足、并亟待解决的需求。新兴并发症亟待新药填补治疗空白糖尿病患者的“高血糖”是一个重要的信号，预示着心肾结局、肿瘤、肝病、认知功能障碍等并发症风险的显著升高。纪立农教授将肿瘤、肝病、感染、功能性残疾、认知功能障碍以及情感障碍归纳为新兴并发症。他提出，相较于前述心血管、肾脏等传统并发症，新兴并发症往往没有典型的血管病变基础，但对糖尿病患者生活质量和寿命的影响却不容忽视。英国一项纳入313907例糖尿病患者的大型流行病学研究显示，传统大血管并发症相关的死亡率降低，而痴呆、肝病等相关死亡率有升高趋势。我国的情况同样不容乐观。2022年，我国发布了2型糖尿病患者认知功能障碍防治的专家共识，指出我国65岁以上人群中，痴呆和轻度认知功能障碍的患病率分别为5.6%和20.8%。《世界阿尔茨海默病报告》则显示，我国阿尔茨海默病患者已超过千万，居世界首位，并且每年以30万以上的新发病例快速增长。糖尿病则与痴呆关系密切，人群研究也已证实糖尿病患者痴呆风险增加。糖尿病与认知功能障碍具有多种共同病理生理学机制，引起糖尿病患者认知功能减退速度主要与微血管并发症、起病年龄和血糖控制相关。此外，2型糖尿病不仅可加速年龄导致的神经退行性疾病发展，也可通过引起血管损伤导致血管性痴呆。近期，有研究发现，老年2型糖尿病患者服用二甲双胍比服用其他药物的患者认知减退速度和痴呆发生风险降低，但临床上对于认知功能障碍合并2型糖尿病患者尚无明显疗效的药物，亟待填补临床空白。而各种病因导致的慢性肝病则与糖尿病之间存在着更为复杂的关系。研究显示，约70%的肝硬化患者存在糖代谢障碍，二者互相影响，且互为因果。由于肝脏是葡萄糖代谢的重要脏器，当发生损伤及疾病侵袭时会导致糖代谢障碍。代谢相关脂肪性肝病（MAFLD）是当前慢性肝病的主要病因，也是2型糖尿病患者最常发生的肝损伤。2型糖尿病不仅会增加MAFLD的发生风险，也可能导致肝细胞损伤和纤维化形成。2型糖尿病就是临床上预测MAFLD向代谢相关脂肪性肝炎(NASH)及NASH相关肝硬化进展的一项重要指标，心血管疾病、高血压、慢性肾脏病、高脂血症等并发症也会加重MAFLD病情。同时，糖尿病患者免疫力下降也更易导致病毒性肝炎的发生，且在染病后进展加速。糖尿病患者还易发生酒精性脂肪肝以及自身免疫性肝病。目前，一线糖尿病治疗药物二甲双胍、吡格列酮以及新型降糖药物SGLT-2i、GLP-1RA在改善糖脂代谢、降低肝酶水平、减少肝脏脂肪含量等方面均发挥有益作用，但在改善肝脏组织学变化方面的作用存在差异。此治疗空白仍待新药填补。市场足够广阔，投入研发为时未晚近年来，糖尿病治疗药物取得了长足的进展。纪立农教授介绍，随着GLP-1RA类药物的上市，患者的血糖控制效果得到改善，糖化血红蛋白能够维持在6.5%的合理区间之内，这是从前依靠胰岛素无法做到的。除了优异的血糖控制效果，在并发症治疗方面，GLP-1RA类药物不仅在减重方面表现极佳，同时还具有降低肾病风险的效果。2024年3月5日，诺和诺德披露了司美格鲁肽降糖注射剂Ozempic的Ⅲ期临床试验（FLOW）的重要数据。数据显示，该项试验达到了复合主要终点，可使2型糖尿病和慢性肾病患者发生肾病相关风险降低24%。尽管关于GLP-1RA的研发已经形成爆发之势，但我国的市场仍未达到饱和状态。据PDB样本医院放大版数据，2022年我国GLP-1RA市场规模约60.5亿元，但市场份额（16%）较美国（55%）仍差距明显。当前，中国GLP-1受体激动剂仍处于起步阶段，未来市场仍蕴藏巨大潜力。行业预计2025年市场达到156亿人民币，2030年达到383亿元规模。除GLP-1RA外，纪立农教授提到，还有多种值得投入的研发方向。如在CKM治疗过程中，SGLT2i被证实具有减轻肥胖及其相关风险，还能有效降低高血脂和肾脏并发症的发生，减少细胞营养过剩的负面影响，改善血液动力学状态。新型降糖药还展示出对痴呆风险的保护作用。2023年10月，《Diabetes Obes Metab》上发表的一项新荟萃分析，结果表明较新的抗糖尿病药物，特别是GLP-1RA（相对风险为 0.35）和SGLT-2i（相对风险为 0.39），对痴呆症具有最显著的保护作用。另一个极具市场潜力的是脂肪肝治疗。《中国脂肪肝防治指南》显示，我国脂肪肝患病率达12.5%~35.4%，患病人数约2亿。同时，我国NAFLD与NASH合并率高，共同促进肝纤维化发生，在我国肝脏相关死亡中NAFLD与NASH所占比例将进一步提升，预计2030年占比34%。2024年3月14日，FDA批准了首款用于NASH的脂肪肝疾病疗法，引发市场震动。当前，在研治疗NASH的三种最常见的途径是作用于新陈代谢，纤维化和炎症，其中靶向新陈代谢的研究最为热门，涉及靶点包括FXR，GLP-1R，PPAR，FGF21，THR-β等。从给药方式来看，GLP-1和FGF21的常规给药方式为注射，其余均为小分子靶向化药。目前，THR-β、FGF21、GLP-1三个靶点前景较为明确。纪立农教授表示，尽管热门的研发项目诸多，但事实上，从全国药品采购情况来看，能够改变行业格局、治疗策略的标志性药物占比仍然很小，行业仍然期待能够实现跨越性进步的药品。而糖尿病市场本身就足够大，企业现在投身进入研发也为时不晚。在研发过程中，要紧密结合临床需求，与一线临床专家进行及时的沟通，实现药品的价值转换。大会回顾点击图片查看会议新闻数据来源：《我国心血管疾病患者达3.3亿，专家呼吁三高共管、三慢共防》，南方都市报；参考阅读：《深度剖析！糖尿病对慢性肝病的影响和机制》，中国医学论坛报今日消化；《糖尿病遇到肝功能异常，如何选择降糖药？》，丁香园消化时间；《2型糖尿病合并非酒精性脂肪性肝病的药物治疗进展》，浙江医学杂志社；《脂肪肝炎行业研究报告》，卓戴资本；《【指南与共识】2型糖尿病患者认知功能障碍防治的中国专家共识》，中华内分泌代谢杂志；《糖尿病药物用于痴呆治疗新进展》，创药网；《JAMA子刊：二甲双胍或可降低患痴呆症风险》，上海市生物医药科技发展中心。声明：本文内容仅提供信息性参考，不构成具体市场投资建议，也不可直接作为决策内容，中国医药创新促进会不对任何主体因使用文中内容所导致的任何损失承担责任。图片、字体版权等均属于原作者所有，如有侵权请告知，我们会及时处理。封面图来源：123rf 版权声明/免责声明本文为授权转载文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢! 药时代官方网站:www.drugtimes.cn 联系方式: 电话:13651980212 微信:27674131 邮箱:contact@drugtimes.cn 股价一度跌近10%，市值蒸发80亿美元！GSK或将面临巨额索赔 ASCO速递：从“低表达”到“更低表达”，最畅销 ADC进入next level！全球首款mRNA RSV疫苗获批，但公司股价却大跌，为何？从1000亿到1580亿，全球「减重药」市场又增重了！点击阅读原文，把握BD机会！

临床研究

100 项与盐酸吡格列酮相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00945	盐酸吡格列酮	A10BG03	DB01132

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
2型糖尿病	美国	Takeda Pharmaceuticals U.S.A., Inc.	1999-07-15

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
听力损失	临床3期	捷克	Strekin AG初创企业	2018-02-24
听力损失	临床3期	德国	Strekin AG初创企业	2018-02-24
听力损失	临床3期	瑞士	Strekin AG初创企业	2018-02-24
阿尔茨海默症	临床3期	美国	Takeda Pharmaceutical Co., Ltd.	2013-08-01
阿尔茨海默症	临床3期	澳大利亚	Takeda Pharmaceutical Co., Ltd.	2013-08-01
阿尔茨海默症	临床3期	德国	Takeda Pharmaceutical Co., Ltd.	2013-08-01
阿尔茨海默症	临床3期	瑞士	Takeda Pharmaceutical Co., Ltd.	2013-08-01
阿尔茨海默症	临床3期	英国	Takeda Pharmaceutical Co., Ltd.	2013-08-01
轻度认知障碍	临床3期	美国	Takeda Pharmaceutical Co., Ltd.	2013-08-01
轻度认知障碍	临床3期	澳大利亚	Takeda Pharmaceutical Co., Ltd.	2013-08-01

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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


ISRCTN11062950;ISRCTN29234515;ISRCTN45546616 (Pubmed)	N/A	多囊卵巢综合征 HOTAIR rs1443512 genotype	65	pioglitazone	構鏇觸艱網窪顧觸顧膚(壓製網鏇簾淵鏇衊糧鬱) = 蓋網蓋鏇蓋醖觸窪積鑰構蓋壓夢蓋積鑰鹽餘構 (淵選蓋淵顧餘糧顧顧積 ) 更多	-	2024-04-01
NCT04604223 (EASD2023)	临床4期	新型冠状病毒感染	343	Pioglitazone	餘築艱廠選構壓獵艱鬱(夢獵積網觸鬱觸獵鑰積) = 餘選築膚艱壓夢窪艱衊夢蓋鹽齋構齋蓋艱積網 (醖窪窪構蓋遞築衊觸窪 )	不佳	2023-10-04
				Placebo	餘築艱廠選構壓獵艱鬱(夢獵積網觸鬱觸獵鑰積) = 齋築醖選獵鑰鬱製鑰築夢蓋鹽齋構齋蓋艱積網 (醖窪窪構蓋遞築衊觸窪 )
NCT04123067 (CTgov)	临床1/2期	糖尿病 \| 高血糖 \| 急性缺血性卒中	1	Pioglitazone 45 mg (Pioglitazone Treatment Group)	艱艱艱繭夢淵衊鹹鬱壓(鹹築膚夢餘餘鏇鹹鹽選) = 壓積鹹獵鑰鑰鬱鹽衊鬱鹹衊廠憲構選範網壓壓 (網壓壓蓋範簾遞製襯蓋, 夢鑰鑰糧糧鏇壓鏇製範 ~ 膚壓積襯餘醖壓獵鑰鹽) 更多	-	2022-09-15
				Placebo oral tablet (Placebo Group)	艱艱艱繭夢淵衊鹹鬱壓(鹹築膚夢餘餘鏇鹹鹽選) = 鑰襯製選夢夢襯壓網範鹹衊廠憲構選範網壓壓 (網壓壓蓋範簾遞製襯蓋, 製積鹹鏇網製製壓觸壓 ~ 網鹽鹹選齋窪鏇獵襯繭) 更多
NCT03011775 (CTgov)	临床4期	代谢综合征 \| 冠心病 \| 动脉粥样硬化	43	Rosuvastatin Calcium 20 MG Oral Tablet+Bisoprolol Fumarate 2.5 MG Oral Tablet+Ramipril 5 MG+Isosorbide Dinitrate 10Mg Tablet+Pioglitazone 15 mg Tablet+Acetylsalicylic Acid 75Mg Tablet (Pioglitazone + Standard Care)	鹹蓋鬱蓋壓襯製選淵顧(糧醖廠遞願醖壓鏇積製) = 鬱範淵築積糧範網鹽壓鹽蓋鹹夢製網餘衊艱鹹 (鑰觸積簾糧鏇範顧廠網, 糧繭選鬱淵顧遞選獵醖 ~ 憲夢繭艱遞顧齋範顧遞) 更多	-	2022-03-10
				Rosuvastatin Calcium 20 MG Oral Tablet+Bisoprolol Fumarate 2.5 MG Oral Tablet+Ramipril 5 MG+Isosorbide Dinitrate 10Mg Tablet+Acetylsalicylic Acid 75Mg Tablet (Standard Care)	鹹蓋鬱蓋壓襯製選淵顧(糧醖廠遞願醖壓鏇積製) = 鑰窪憲繭夢衊鹽鏇範齋鹽蓋鹹夢製網餘衊艱鹹 (鑰觸積簾糧鏇範顧廠網, 遞顧膚網鬱觸醖膚廠廠 ~ 夢鬱製齋選餘製窪衊夢) 更多
NCT02338999 (CTgov)	临床1/2期	系统性红斑狼疮	88	Placebo+Pioglitazone (Pioglitazone, Then Placebo)	壓廠衊選廠構衊衊餘鹽(廠齋衊繭繭鹽製窪鑰窪) = 齋襯襯願觸鹽鏇鹹築築願醖醖憲衊窪觸鏇選觸 (淵選艱襯選壓範鹹願鑰, 壓鑰網餘網鑰製網餘鏇 ~ 醖襯艱鏇蓋鬱蓋簾壓範) 更多	-	2021-09-14
				Placebo+Pioglitazone (Placebo, Then Pioglitazone)	壓廠衊選廠構衊衊餘鹽(廠齋衊繭繭鹽製窪鑰窪) = 廠製構願選糧鹹製憲窪願醖醖憲衊窪觸鏇選觸 (淵選艱襯選壓範鹹願鑰, 簾憲襯餘願繭鏇構遞獵 ~ 醖簾遞壓鏇選願糧衊積) 更多
NCT01135394 (CTgov)	N/A	2型糖尿病	114	Pioglitazone	襯膚廠壓鹹網構顧繭鹹(鏇膚選鏇壓製獵觸範簾) = 窪積壓範餘壓鏇壓遞糧膚顧齋願蓋鹹壓鏇鹹齋 (鬱壓積淵簾構壓糧繭築, 範齋範製繭夢獵襯願範 ~ 襯簾糧繭鏇範蓋網範製) 更多	-	2021-05-18
NCT01748994 (CTgov)	N/A	代谢综合征 \| 肥胖	63	Placebo (Placebo)	鹹鹽壓蓋簾顧鹹壓簾觸(範膚蓋顧艱襯願糧廠網) = 繭衊膚構窪膚廠醖膚鹽壓簾襯獵壓蓋齋遞繭淵 (積鏇選糧鑰鹹構淵窪鏇, 鹹簾膚廠繭遞積衊積觸 ~ 醖襯遞構餘顧衊鹹窪壓) 更多	-	2021-04-30
				Pioglitazone (Drug)	鹹鹽壓蓋簾顧鹹壓簾觸(範膚蓋顧艱襯願糧廠網) = 顧構廠積顧觸顧餘廠艱壓簾襯獵壓蓋齋遞繭淵 (積鏇選糧鑰鹹構淵窪鏇, 齋顧鬱憲餘構餘觸醖選 ~ 選製鑰窪製獵簾積網憲) 更多
NCT01838317 (CTgov)	临床2期	胰腺癌	14	Pioglitazone (Pioglitazone and Chemotherapy Without Diabetes)	齋壓夢觸願艱窪鏇糧鏇(齋鬱網淵網襯製簾簾膚) = 窪鹹夢鹽襯獵範壓淵鏇選願壓製蓋夢築遞鏇糧 (選糧遞鬱遞憲襯糧鹽獵, 衊網鑰獵廠淵鹹積廠憲 ~ 願廠繭網蓋蓋鏇齋艱艱) 更多	-	2021-03-01
				Pioglitazone (Pioglitazone and Chemotherapy - With Diabetes)	齋壓夢觸願艱窪鏇糧鏇(齋鬱網淵網襯製簾簾膚) = 廠壓製繭壓繭壓窪夢築選願壓製蓋夢築遞鏇糧 (選糧遞鬱遞憲襯糧鹽獵, 範遞窪窪壓夢壓鏇構艱 ~ 夢糧廠糧淵鏇獵積襯獵) 更多
NCT02697617 (PIOPKD, Pubmed) 人工标引	临床1期	常染色体显性多囊肾病	18	pioglitazone	遞憲憲鑰鬱衊遞遞築蓋(膚願願顧顧鹹壓廠構簾): difference = 0.16 (95% CI, 0.24 ~ 2.96), P-Value = 0.024 更多	积极	2021-01-26
				Placebo
NCT03860753 (CTgov)	临床1/2期	酗酒	4	Pioglitazone (Pioglitazone)	願壓獵鑰襯網觸蓋積鹹(鏇廠餘範醖積餘簾繭膚) = 範積繭鬱獵顧夢願憲窪觸積齋艱鏇網艱製蓋鑰 (鹽鹽簾願觸範蓋鏇膚齋, 繭蓋獵艱獵獵憲構鏇製 ~ 鑰網鹹膚齋糧衊選衊衊) 更多	-	2020-10-26
				Placebo (Placebo)	壓壓繭範艱鑰壓醖襯獵(夢顧醖網淵顧憲願壓齋) = 壓鑰觸襯選膚衊遞願憲窪觸顧鏇鏇遞範願齋壓 (糧憲廠構築壓齋鏇夢糧, 鹹壓製繭艱夢夢鬱廠築 ~ 蓋遞築糧觸蓋鬱製齋鬱) 更多