二甲双胍马来酸罗格列酮(Metformin Hydrochloride/Rosiglitazone Maleate) - 药物靶点：PPARγ x PRKAB1_在研适应症：2型糖尿病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Avandamet、Avandamet XR、Metformin Hydrochloride and Rosiglitazone Maleate

+ [5]

靶点

PPARγ x PRKAB1

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)、PRKAB1激活剂(腺苷酸活化蛋白激酶亚基β1激活剂)

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-

原研机构

GSK Plc

在研机构

Glenmark Pharmaceuticals Ltd.Glaxosmithkline Australia Pty Ltd.

非在研机构

GSK PlcSmithkline Beecham PlcSB Pharmco Puerto Rico, Inc.

+ [1]

最高研发阶段批准上市

首次获批日期

美国 (2002-10-10),

2型糖尿病

最高研发阶段(中国)批准上市

特殊审评-

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结构/序列

分子式C26H35ClN8O7S

InChIKeyUABJPASVFPMIGE-KWZUVTIDSA-N

CAS号622402-70-4

关联

17

项与二甲双胍马来酸罗格列酮相关的临床试验

NCT01332071

/ Completed临床1期

Assessment of Relative Bioavailability of Avandamet 4 mg + 1000 mg (GSK) in the Form of Film Coated Tablets Versus Avandamet 2 mg + 500 mg (GSK) in the Form of Film Coated Tablets, in Healthy Volunteers After Feeding Standardized, Using Liquid Chromatography.

The study is prospective, open-label, randomized, crossover, with 02 treatments, 02 sequences, and 02 periods. The volunteers received, in each period, the reference or the test formulation after standardized meals.

开始日期2009-11-24

申办/合作机构

GSK Plc

ChiCTR-TRC-13003776

/ Completed临床4期IIT

Efficacy and safety of avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone

开始日期2009-11-19

申办/合作机构-

NCT00933309

/ Completed临床1期IIT

The Impact of Obesity and Obesity Treatments on Breast Cancer: A Phase I Trial of Exemestane With Metformin and Rosiglitazone for Postmenopausal Obese Women With ER+ Metastatic Breast Cancer

The goal of this clinical research study is to find the highest tolerable dose of Avandamet that can be given in combination with exemestane to patients who are obese and postmenopausal with hormone-receptive-positive breast cancer that has spread to other parts of the body.

开始日期2009-07-01

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

100 项与二甲双胍马来酸罗格列酮相关的临床结果

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100 项与二甲双胍马来酸罗格列酮相关的转化医学

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100 项与二甲双胍马来酸罗格列酮相关的专利（医药）

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15

项与二甲双胍马来酸罗格列酮相关的文献（医药）

2019-12-01·Cancer Cell International3区 · 医学

Rosiglitazone metformin adduct inhibits hepatocellular carcinoma proliferation via activation of AMPK/p21 pathway

3区 · 医学

ArticleOA

作者: Chen, Ke ; Hu, Xiangnan ; Shan, Xuefeng ; Tang, Hua ; Liu, Yuyang

BACKGROUNDRosiglitazone metformin adduct (RZM) is a novel compound, synthesized from rosiglitazone (Ros) and metformin (Met) combined at a molar mass ratio of 1:1. Met and Ros are widely used together for treating type 2 diabetes to improve drug effectiveness and reduce adverse drug reactions. Recent studies reported that both Met and Ros may possess antineoplastic properties in several cancers, including hepatocellular carcinoma (HCC). However, the effects of RZM in HCC and its underlying mechanisms remain unknown.METHODSRZM was synthesized from Ros and Met at an equal molar ratio and identified by infrared spectroscopy. MTS and colony formation assays were performed to detect proliferative repression of RZM, the mixture, Met and Ros, respectively. Tumorigenesis assay in vivo was used to confirm the anti-tumorigenesis potential of RZM and Met. Moreover, cellular apoptosis caused by RZM was analyzed by hoechst staining assay and flow cytometry. RT-qPCR and western blotting were performed to reveal mechanisms for the function of RZM.RESULTSBoth in vitro and in vivo data showed that low doses of RZM enhanced inhibitory effect on HCC cells growth compared with Met. Flow cytometry analysis confirmed that treatment with RZM at 1 mM for 48 h triggered HCC cells apoptosis. RT-qPCR and western blotting analyses showed that p21 was upregulated in response to 1 mM RZM treatment. Furthermore, RZM could increase AMPK activation compared with Met. The increased p21 expression induced by RZM treatment was attenuated by an AMPK inhibitor compound C.CONCLUSIONSAll these observations demonstrate that RZM increases the antiproliferative effect of Met in HCC via upregulating p21 expression in an AMPK-dependent manner. Our results suggest that RZM has the potential to be an adjuvant for HCC therapy.

2015-05-20·Chinese Medical Journal3区 · 医学

Efficacy and Safety of Avandamet or Uptitrated Metformin Treatment in Patients with Type 2 Diabetes Inadequately Controlled with Metformin Alone

3区 · 医学

ArticleOA

作者: Jia-Jun Zhao ; Ying-Li Chen ; Wei Gu ; Xiao-Ling Cai ; Jin-Kui Yang ; Cheng-Jiang Li ; Hua-Zhang Yang ; Li-Nong Ji ; Zhong-Yan Shan ; Hao-Ming Tian ; Tian-Pei Hong ; Ming-Cai Qiu ; Yao-Ming Xue

BACKGROUNDAt present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone.METHODSThis study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment.RESULTSAt week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 μU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 μU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups.CONCLUSIONSCompared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated.REGISTRATION NUMBERChiCTR-TRC-13003776.

2013-01-01·Folia Biologica4区 · 医学

Correlated Increase of Omentin-1 and Adiponectin by Exenatide, Avandamet and Dietary Change in Diet-Induced Obese Rats

4区 · 医学

Article

作者: Yuan, X-W ; Zhu, D-L ; Wang, W-M ; Feng, W-H ; Yang, D-H ; Xiang, S-K ; Bi, Y ; Liu, Y-Q ; Hu, J ; Tong, G-Y ; Shao, L-L ; Li, P ; Hu, Y ; Dai, Y-Y ; Shen, S-M

Adipokines omentin-1 and adiponectin have been reported to improve insulin resistance. It is known that insulin sensitizers exenatide, avandamet, or diet change from high-fat to normal chow ameliorate metabolic disorders. However, whether these treatments increase omentin-1 levels in high fat-diet animals and the relationship between omentin-1 and adiponectin remain largely unknown. We investigated the effect of insulin sensitizers exenatide and avandamet, and of dietary change on these adipokine levels, body weight, and insulin sensitivity in diet-induced obese rats. Obesity was induced in rats by high-fat diet feeding for 8 weeks, and then the rats were given exenatide, avandamet and diet change to normal chow, respectively, for additional 8 weeks. Compared to the high-fat control group, exenatide and avandamet treatment significantly induced adipose gene expression and elevated the circulation levels of omentin-1 and adiponectin, whereas they decreased the leptin gene expression and circulation level, which is associated with improvement of systemic insulin sensitivity and the glucose and lipid profile. Notably, there was a significant positive correlation between omentin-1 and adiponectin in the above regimens, suggesting that omentin-1 and adiponectin may contribute to the insulin-sensitizing effect of exenatide and avandamet.

100 项与二甲双胍马来酸罗格列酮相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	A10BD03	-

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	印度	Glenmark Pharmaceuticals Ltd.	2004-01-22

未上市

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适应症	最高研发状态	国家/地区	公司	日期
2型糖尿病	临床前	美国	SB Pharmco Puerto Rico, Inc.	2002-10-10

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临床结果

适应症

分期

评价

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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


NCT00131664 (AVALANCHE, CTgov)	临床3期	2型糖尿病	391	Amaryl (Avandia and Amaryl)	選選憲艱網簾鏇鏇簾膚(淵艱鏇齋壓衊壓膚繭膚) = 醖衊蓋網膚艱窪艱糧廠膚窪顧積積壓網範鏇願 (廠蓋觸醖壓遞蓋衊廠窪, 膚廠膚壓鹽壓選餘淵齋 ~ 醖選壓憲範憲齋夢範積) 更多	-	2013-04-17
				Avandamet (Avandamet)	選選憲艱網簾鏇鏇簾膚(淵艱鏇齋壓衊壓膚繭膚) = 糧夢簾鬱糧壓顧顧遞鑰膚窪顧積積壓網範鏇願 (廠蓋觸醖壓遞蓋衊廠窪, 網膚繭遞遞觸鹽窪蓋鏇 ~ 淵窪鑰艱鑰艱製鏇餘鏇) 更多
NCT01332071 (CTgov)	临床1期	2型糖尿病	26	Rosiglitazone Maleate (Test Product)	憲簾醖積醖觸蓋製製蓋(鹹襯鏇積襯選觸製膚壓) = 齋鏇繭鬱範積構襯糧鹹製鑰衊觸願壓鏇衊艱鬱 (築壓觸範製糧廠築構艱, 遞蓋餘鏇夢膚遞選繭製 ~ 鹽鏇構餘襯簾觸夢齋範) 更多	-	2011-04-08
				Rosiglitazone Maleate (Reference Product)	憲簾醖積醖觸蓋製製蓋(鹹襯鏇積襯選觸製膚壓) = 壓鬱蓋夢齋構淵製積鹹製鑰衊觸願壓鏇衊艱鬱 (築壓觸範製糧廠築構艱, 網淵鹹鬱艱艱網襯窪繭 ~ 觸糧淵淵築願鏇艱簾醖) 更多