Delving into the Latest Updates on Metformin Hydrochloride/Pioglitazone Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

ACTOplus met, Competact, Glubrava

+ [16]

Target

PPARγ x PRKAB1

Action

agonists, activators

Mechanism

PPARγ agonists(Peroxisome proliferator-activated receptor γ agonists), PRKAB1 activators(Protein kinase AMP-activated non-catalytic subunit beta 1 activators)

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication

Diabetes Mellitus, Type 2

Inactive Indication

DyslipidemiasInfectious DiseasesMetabolic Syndrome+ [1]

Originator Organization

Takeda Pharmaceutical Co., Ltd.

Active Organization

CHEPLAPHARM Arzneimittel GmbH

Hangzhou Zhongmeihuadong Pharmaceutical Co., Ltd.T’s Pharma Co., Ltd.

+ [2]

Inactive Organization

Takeda Pharma A/S

License Organization-

Drug Highest PhaseApproved

First Approval Date

United States (29 Aug 2005),

Diabetes Mellitus, Type 2

Regulation-

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Structure/Sequence

Molecular FormulaC23H33Cl2N7O3S

InChIKeyQQPUCHJKWMHONF-UHFFFAOYSA-N

CAS Registry737811-27-7

北京太洋药业股份有限公司研制的吡格列酮二甲双胍片（15 mg/500 mg）与武田テバ薬品株式会社持证的吡格列酮二甲双胍片（メタクト配合錠LD®，15 mg/500 mg）在中国健康受试者中进行的随机、开放、单剂量、两周期、双交叉设计的空腹及餐后状态下的生物等效性研究

[Translation] A randomized, open-label, single-dose, two-period, double-crossover bioequivalence study was conducted in healthy Chinese subjects between pioglitazone-metformin tablets (15 mg/500 mg) developed by Beijing Taiyang Pharmaceutical Co., Ltd. and pioglitazone-metformin tablets (Metact LD®, 15 mg/500 mg) licensed by Takeda Teba Pharmaceutical Co., Ltd., under fasting and fed conditions.

以北京太洋药业股份有限公司研制的吡格列酮二甲双胍片（规格：15 mg/500 mg）为受试制剂，持证商为武田テバ薬品株式会社的吡格列酮二甲双胍片（商品名：メタクト配合錠LD®，规格：15 mg/500 mg）为参比制剂，考察两制剂在空腹及餐后状态下单次给药的药代动力学参数及相对生物利用度，评价两制剂是否具有生物等效性。同时评价两种制剂在健康人体中的安全性和耐受性。

[Translation]

The test formulation, pioglitazone-metformin tablets (15 mg/500 mg) developed by Beijing Taiyang Pharmaceutical Co., Ltd., and the reference formulation, pioglitazone-metformin tablets (Metact LD®, 15 mg/500 mg) from Takeda Teba Pharmaceuticals, were used. The pharmacokinetic parameters and relative bioavailability of the two formulations following single administration in the fasting and fed states were investigated to evaluate their bioequivalence. The safety and tolerability of the two formulations in healthy volunteers were also evaluated.

Start Date26 Sep 2025

Sponsor / Collaborator

Beijing Taiyang Pharmaceutical Co. Ltd.

CTR20252899

/ CompletedNot Applicable

吡格列酮二甲双胍片人体生物等效性研究

[Translation] Study on the bioequivalence of pioglitazone and metformin tablets in healthy volunteers

本试验旨在研究单次空腹和餐后口服浙江诺得药业有限公司研制、生产的吡格列酮二甲双胍片（15 mg/500 mg）的药代动力学特征；以武田テバ薬品株式会社持证、生产的吡格列酮二甲双胍片（メタクト配合錠LD®，15 mg/500 mg）为参比制剂，比较两制剂中药动学参数Cmax、AUC0-t、AUC0-∞，评价两制剂的人体生物等效性。

[Translation]

This study aimed to investigate the pharmacokinetic characteristics of a single fasting and postprandial oral administration of pioglitazone metformin tablets (15 mg/500 mg) developed and produced by Zhejiang Nordex Pharmaceutical Co., Ltd.; using pioglitazone metformin tablets (Metact® LD®, 15 mg/500 mg) licensed and produced by Takeda Teba Pharmaceutical Co., Ltd. as the reference preparation, to compare the pharmacokinetic parameters Cmax, AUC0-t, and AUC0-∞ of the two preparations, and to evaluate the bioequivalence of the two preparations in humans.

Start Date16 Aug 2025

Sponsor / Collaborator

Zhejiang NuoDe Pharmaceutical Co., Ltd.

CTR20252801

/ CompletedNot Applicable

石家庄市普力制药有限公司研制的吡格列酮二甲双胍片（15 mg/500 mg）与武田テバ薬品株式会社持证的吡格列酮二甲双胍片（メタクト配合錠LD®，15 mg/500 mg）在中国健康受试者中进行的随机、开放、单剂量、两周期、双交叉设计的空腹及餐后状态下的生物等效性研究

[Translation] A randomized, open-label, single-dose, two-period, double-crossover design bioequivalence study of pioglitazone-metformin tablets (15 mg/500 mg) developed by Shijiazhuang Puli Pharmaceutical Co., Ltd. and pioglitazone-metformin tablets (Metact LD®, 15 mg/500 mg) licensed by Takeda Teba Pharmaceutical Co., Ltd. in Chinese healthy subjects under fasting and fed conditions

以石家庄市普力制药有限公司研制的吡格列酮二甲双胍片（规格：15 mg/500 mg）为受试制剂，持证商为武田テバ薬品株式会社的吡格列酮二甲双胍片（商品名：メタクト配合錠LD®，规格：15 mg/500 mg）为参比制剂，考察两制剂在空腹及餐后状态下单次给药的药代动力学参数及相对生物利用度，评价两制剂是否具有生物等效性。同时评价两种制剂在健康人体中的安全性和耐受性。

[Translation]

Pioglitazone metformin tablets (specification: 15 mg/500 mg) developed by Shijiazhuang Puli Pharmaceutical Co., Ltd. were used as the test preparation, and pioglitazone metformin tablets (trade name: Metact LD®, specification: 15 mg/500 mg) from Takeda Teba Pharmaceutical Co., Ltd. were used as the reference preparation. The pharmacokinetic parameters and relative bioavailability of the two preparations after single administration in the fasting and postprandial states were investigated to evaluate whether the two preparations were bioequivalent. At the same time, the safety and tolerability of the two preparations in healthy humans were evaluated.

Start Date09 Aug 2025

Sponsor / Collaborator

Shijiazhuang Puli Pharmaceutical Co Ltd.

100 Clinical Results associated with Metformin Hydrochloride/Pioglitazone Hydrochloride

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100 Translational Medicine associated with Metformin Hydrochloride/Pioglitazone Hydrochloride

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100 Patents (Medical) associated with Metformin Hydrochloride/Pioglitazone Hydrochloride

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11

Literatures (Medical) associated with Metformin Hydrochloride/Pioglitazone Hydrochloride

01 Jan 2017·Journal of clinical medicine research

Effect of Switching From an Anti-Diabetic Loose Dose Combination to a Fixed Dose Combination Regimen at Equivalent Dosage for 6 Months on Glycemic Control in Japanese Patients With Type 2 Diabetes: A Pilot Study

Article

Author: Oka, Masanao ; Kamiyama, Hiroshi ; Aoki, Kazutaka ; Masumura, Makoto ; Nagakura, Mieko ; Taguri, Masataka ; Furuie, Tadashi ; Terauchi, Yasuo ; Akema, Noriko ; Nakajima, Shigeru ; Kamiko, Kazunari

BACKGROUND:

Patients with type 2 diabetes mellitus often take multiple anti-diabetic drugs for a long period. Fixed dose combination (FDC) therapy is expected to improve drug adherence for patients with diabetes. The effect of switching from a loose dose combination (LDC) regimen to an FDC regimen at equivalent dosage on glycemic control has not been evaluated fully. Therefore, we investigated the effect of switching from LDC to FDC at equivalent dosage for 6 months on glycemic control in Japanese patients with type 2 diabetes.

METHODS:

Thirty-eight Japanese patients with type 2 diabetes who were taking anti-diabetic drugs including pioglitazone + metformin, pioglitazone + alogliptin, or pioglitazone + glimepiride were enrolled. These drugs were switched to an FDC of Metact^®, Liobel^® or Sonias^®, respectively, at equivalent dosage. Other anti-diabetic drugs and units of insulin were not changed during the study if possible. HbA1c and body weight were measured 0, 2, 4 and 6 months after switching from an LDC to FDC. We also conducted a questionnaire survey 2 months after the start of the FDC regimen.

RESULTS:

HbA1c levels at 2, 4, and 6 months were not significantly changed compared with prior to switching from an LDC to FDC regimen. Moreover, 74.2% of patients considered decreasing the number of drugs to be "very good" or "good".

CONCLUSION:

HbA1c levels did not differ between patients receiving LDC and FDC therapy at equivalent dosage in this study.

01 Dec 2016·Die PharmazieQ4 · MEDICINE

A guide for using experimental design in chromatographic method development: applied to the analysis of selected anti-diabetic pharmaceutical combinations.

Q4 · MEDICINE

Article

Author: Abdel-Aziz, O. ; Ayoub, B. M.

A guide experimental design in chromatographic method development was described and applied successfully to the analysis of different recently approved anti-diabetic pharmaceutical combinations. Enhancement of UHPLC analysis of alogliptin benzoate either with pioglitazone hydrochloride or with metformin hydrochloride was achieved. The optimal chromatographic conditions were not attained by trial and error that requires a large number of experiments. Alternatively, a computer program was used as a systematic optimization strategy for the design of the experiment which accurately predicts the combined effect of different factors simultaneously. Resolution between peaks was studied by the proposed fractional factorial design approach performed by the Minitab® Program using screening and optimization steps. Application of the central composite design was implemented. A Pareto chart was used to exclude the insignificant variables. Linearity ranges were found to be 0.5-40 μg ml-1, 1-20 μg ml-1 and 1-32 μg ml-1 for alogliptin benzoate, pioglitazone hydrochloride and metformin hydrochloride, respectively. The proposed method is applicable for the analysis of six pharmaceutical dosage forms namely, Nesina®, Actos®, Glucophage®, Oseni®, Kazano® and Actoplus MET® tablets.

01 Jul 2011·Regulatory toxicology and pharmacology : RTPQ4 · MEDICINE

Evaluation of carcinogenicity studies of medicinal products for human use authorised via the European centralised procedure (1995–2009)

Q4 · MEDICINE

Article

Author: Olejniczak, Klaus ; Friedrich, Anita

Carcinogenicity data of medicinal products for human use that have been authorised via the European centralised procedure (CP) between 1995 and 2009 were evaluated. Carcinogenicity data, either from long-term rodent carcinogenicity studies, transgenic mouse studies or repeat-dose toxicity studies were available for 144 active substances contained in 159 medicinal products. Out of these compounds, 94 (65%) were positive in at least one long-term carcinogenicity study or in repeat-dose toxicity studies. Fifty compounds (35%) showed no evidence of a carcinogenic potential. Out of the 94 compounds with positive findings in either carcinogenicity or repeat-dose toxicity studies, 33 were positive in both mice and rats, 40 were positive in rats only, and 21 were positive exclusively in mice. Long-term carcinogenicity studies in two rodent species were available for 116 compounds. Data from one long-term carcinogenicity study in rats and a transgenic mouse model were available for eight compounds. For 13 compounds, carcinogenicity data were generated in only one rodent species. One compound was exclusively tested in a transgenic mouse model. Six compounds were tumourigenic in repeat-dose toxicity studies in rats. The majority of tumour findings observed in rodent carcinogenicity studies were considered not to be relevant for humans, either due to a rodent-specific mechanism of carcinogenicity, a high safety margin between exposures at the NOAEL (No Observed Adverse Effect Level) in rodents and recommended therapeutic doses in humans, or based on historical control data, a small effect size and lack of dose-response relationship and tumours typically observed in rodent strains used, or were considered not to be relevant for humans based on literature and clinical data or likely differences in metabolism/local concentrations between rodents and humans. Due to the high number of rodent tumour findings with unlikely relevance for humans, the value of the currently used testing strategy for carcinogenicity appears questionable. A revision of the carcinogenicity testing paradigm is warranted.

1

News (Medical) associated with Metformin Hydrochloride/Pioglitazone Hydrochloride

12 Aug 2024

·www.echemi.com

The Race for China's Next Top Diabetes Drug: Winsunny Pharmaceutical and Yiheng Pharma Vie for Pioglitazone and Metformin Combination

On August 8, the official website of China Medical Science and Technology Achievements Transformation Center (CDE) released a news that Beijing Winsunny Pharmaceutical and Nanjing EASEHEAL Pharmaceutical two companies of pioglitazone metformin tablet generic drug listing application has been officially accepted. The news quickly garnered widespread attention as it heralded the arrival of a new player in a high-profile drug market competition. Pioglitazone metformin tablets are a drug widely used to improve blood sugar control in people with type 2 diabetes. In 2023, the drug's sales in the national hospital market have exceeded 1 billion yuan, a year-on-year increase of 14.09%, ranking 12th in the diabetes treatment drug market, according to data from Yaofongyun. At present, only two companies in the market, Jiangsu Deyuan Pharma and Hangzhou Huadong Medicine, have been approved for production and passed the consistency evaluation. Pioglitazone metformin tablets are a diabetes treatment made from a combination of two active ingredients: metformin and pioglitazone. It is primarily used to treat type 2 diabetes. Its dual action mechanism is embodied in the following two aspects: First, pioglitazone effectively promotes the conversion and utilization of glucose in muscle and adipose tissue by improving the body's sensitivity to insulin, thereby improving the body's ability to regulate blood sugar. Secondly, metformin further reduces blood sugar levels by inhibiting the production of glucose in the liver, thus achieving effective control of blood sugar. The drug is effective, can effectively control fasting blood glucose and postprandial blood glucose, improve the metabolic disorders of diabetes. It can also delay the development of type 2 diabetes and prevent and reduce the occurrence of complications. Pioglitazone metformin tablets have a good safety profile, do not cause common insulin treatment side effects such as hypoglycemia, and can reduce the risk of cardiovascular disease, cardiometabolic protection. In addition, the drug only needs to be taken once a day and is convenient to administer, helping to improve patient compliance. The application of Beijing Winsunny Pharmaceutical and Nanjing EASEHEAL Pharmaceutical was accepted, indicating that China will have a third pharmaceutical company qualified to produce this diabetes treatment drug. This will undoubtedly provide more options for patients and could increase competition among Chinese pharmaceutical companies. In recent years, Beijing Winsunny Pharmaceutical has been active in the application of new drugs, including 18 varieties including bromohexine hydrochloride oral solution, Lansoprazole enteric capsules, etc., are being declared. Nanjing EASEHEAL Pharmaceutical also recently has a number of generic drugs in the review stage, such as voriconazole dry suspension, Indapamide sustained-release tablets. With the addition of more players, the pioglitazone metformin tablet market is expected to become more diversified, offering more quality treatment options for patients with diabetes. This will undoubtedly drive continued innovation in the field and let us look forward to the future.

Drug Approval

100 Deals associated with Metformin Hydrochloride/Pioglitazone Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	A10BD05	-

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Infectious Diseases	United States	Takeda Pharmaceuticals U.S.A., Inc.	12 May 2009
Weight Loss	United States	Takeda Pharmaceuticals U.S.A., Inc.	12 May 2009
Diabetes Mellitus, Type 2	United States	Takeda Pharmaceuticals U.S.A., Inc.	29 Aug 2005

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Dyslipidemias	Phase 3	Germany	Takeda Pharmaceutical Co., Ltd.	01 Apr 2007
Metabolic Syndrome	Phase 3	-	Takeda Pharmaceutical Co., Ltd.	01 Jan 2007

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ChiCTR1900028606 (OP 43, EASD2023)	Phase 4	Diabetes Mellitus, Type 2 First line	-	Pioglitazone/metformin FDC	eytnafohor(kgglcmkyre) = jlrexhvcpv gprrqanadk (spinqcrhac, 0.08) View more	Positive	06 Oct 2023
				Uptitrated metformin	eytnafohor(kgglcmkyre) = meyhoecwye gprrqanadk (spinqcrhac, 0.08) View more
NCT02917629 (CTgov)	Phase 2	Squamous Cell Carcinoma of the Oropharynx \| Squamous cell carcinoma of the oral cavity \| Squamous Cell Carcinoma	6	Pharmacological Study+Metformide Hydrochloride/Pioglitazone Hydrochloride Extended-Release Tablet (Group I (ACTOplus Met XR))	aykeooclwn(gadsklennj) = cibwyejtjc zwycwaulaa (kdynilozbl, juthkecoya - nbagmxstsr) View more	-	08 Mar 2023
				Placebo (Group II (Placebo))	aykeooclwn(gadsklennj) = snaolccnyz zwycwaulaa (kdynilozbl, fwjsmetbqa - ugkjvtempr) View more
NCT00362440 (CTgov)	Phase 2	Metabolic Syndrome \| Lipodystrophy	9	Leptin+Pioglitazone or metformin (Leptin)	booiowkral(mtufayceck) = mqfyhkqbbe bptutmnyvb (ggisoyezfa, 0.5) View more	-	23 Mar 2017
				Placebo+Pioglitazone or metformin (Pioglitazone or Metformin)	booiowkral(mtufayceck) = iogqvausni bptutmnyvb (ggisoyezfa, 0.8) View more
NCT02099838 (CTgov)	Phase 4	Diabetes Mellitus, Type 2	98	Pioglitazone and Metformin (Pioglitazone and Metformin)	htuduijfyt(btjikbmcjm) = mdsuwirokv siefzwfexa (qbsrsvjgfh, 0.12) View more	-	10 Jun 2014
				Placebo (Placebo)	htuduijfyt(btjikbmcjm) = iukmnxdsek siefzwfexa (qbsrsvjgfh, 0.14) View more
NCT00770653 (PIOfix, Pubmed \| Diabetes Technol Ther)	Phase 3	Dyslipidemias	288	Pioglitazone/Metformin Fixed Combination	tridlrwram(bwgwindzzq) = oiqipktohx akchmterbi (wuzjycxodc ) View more	-	01 Jun 2011
				Combination of Metformin with Glimepiride	tridlrwram(bwgwindzzq) = idfbujnszw akchmterbi (wuzjycxodc ) View more
NCT00770653 (PIOfix, CTgov)	Phase 3	Diabetes Mellitus, Type 2 \| Dyslipidemias	305	Pioglitazone and Metformin (Pioglitazone 15 mg and Metformin 850 mg BID)	sbtgiasczw(gbrlfxdnpw) = gqmqmjucfi mhetveayao (pfkxfxqsil, 9.7) View more	-	06 Oct 2010
				Metformin+Glimepiride (Glimepiride 2 mg and Metformin 850 mg BID)	sbtgiasczw(gbrlfxdnpw) = crqqexxqnp mhetveayao (pfkxfxqsil, 11.0) View more
NCT00727857 (ClinicalTrials.gov, CTgov)	Phase 3	Diabetes Mellitus, Type 2	600	Pioglitazone (Pioglitazone 15 mg BID)	qcvlvcqbal(nvimcajapa) = cdcjporszb teuuedioht (axlfatrbed, 0.131) View more	-	09 Mar 2010
				Metformin (Metformin 850 mg BID)	qcvlvcqbal(nvimcajapa) = asniuixagv teuuedioht (axlfatrbed, 0.120) View more
NCT00727857 (ClinicalTrials.gov, Pubmed \| Curr Med Res Opin)	Phase 3	Diabetes Mellitus, Type 2	600	Pioglitazone/metformin FDC	agzebpcctn(zgybovqncw) = pwffrvjufi zqcqpybocx (emfjldnhbu ) View more	Positive	01 Dec 2009
				Pioglitazone	agzebpcctn(zgybovqncw) = qcyrcycbgs zqcqpybocx (emfjldnhbu )