Metformin hydrochloride; pioglitazone hydrochloride - Generic Drug Details

What are the generic drug sources for metformin hydrochloride; pioglitazone hydrochloride and what is the scope of freedom to operate?

Metformin hydrochloride; pioglitazone hydrochloride is the generic ingredient in three branded drugs marketed by Takeda Pharms Usa, Aurobindo Pharma Ltd, Chartwell Rx, Macleods Pharms Ltd, Pharmobedient, Teva Pharms Usa, and Torrent Pharms Ltd, and is included in eight NDAs. There are four patents protecting this compound and two Paragraph IV challenges. Additional information is available in the individual branded drug profile pages.

Metformin hydrochloride; pioglitazone hydrochloride has one hundred and thirteen patent family members in thirty-two countries.

Seven suppliers are listed for this compound.

Summary for metformin hydrochloride; pioglitazone hydrochloride

International Patents:	113
US Patents:	4
Tradenames:	3
Applicants:	7
NDAs:	8
Finished Product Suppliers / Packagers:	7
Clinical Trials:	165
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for metformin hydrochloride; pioglitazone hydrochloride
DailyMed Link:	metformin hydrochloride; pioglitazone hydrochloride at DailyMed

Recent Clinical Trials for metformin hydrochloride; pioglitazone hydrochloride

Identify potential brand extensions & 505(b)(2) entrants

Sponsor	Phase
Boryung Pharmaceutical Co., Ltd	PHASE1
Sun Yat-sen University	PHASE3
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	PHASE3

See all metformin hydrochloride; pioglitazone hydrochloride clinical trials

Pharmacology for metformin hydrochloride; pioglitazone hydrochloride

Drug Class	Biguanide Peroxisome Proliferator Receptor alpha Agonist Peroxisome Proliferator Receptor gamma Agonist Thiazolidinedione
Mechanism of Action	Peroxisome Proliferator-activated Receptor alpha Agonists Peroxisome Proliferator-activated Receptor gamma Agonists Peroxisome Proliferator-activated Receptor Activity

Anatomical Therapeutic Chemical (ATC) Classes for metformin hydrochloride; pioglitazone hydrochloride

A10BA	Biguanides
A10B	BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
A10	DRUGS USED IN DIABETES
A	Alimentary tract and metabolism

A10BG	Thiazolidinediones
A10B	BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
A10	DRUGS USED IN DIABETES
A	Alimentary tract and metabolism

Paragraph IV (Patent) Challenges for METFORMIN HYDROCHLORIDE; PIOGLITAZONE HYDROCHLORIDE

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
ACTOPLUS MET XR	Extended-release Tablets	metformin hydrochloride; pioglitazone hydrochloride	15 mg/1000 mg and 30 mg/1000 mg	022024	1	2011-09-23

US Patents and Regulatory Information for metformin hydrochloride; pioglitazone hydrochloride

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Takeda Pharms Usa	ACTOPLUS MET	metformin hydrochloride; pioglitazone hydrochloride	TABLET;ORAL	021842-001	Aug 29, 2005		DISCN	Yes	No	9,101,660		Y
Takeda Pharms Usa	ACTOPLUS MET XR	metformin hydrochloride; pioglitazone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	022024-001	May 12, 2009		DISCN	Yes	No	7,785,627		Y
Aurobindo Pharma Ltd	PIOGLITAZONE HYDROCHLORIDE AND METFORMIN HYDROCHLORIDE	metformin hydrochloride; pioglitazone hydrochloride	TABLET;ORAL	200823-001	Feb 13, 2013	AB	RX	No	No
Takeda Pharms Usa	ACTOPLUS MET XR	metformin hydrochloride; pioglitazone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	022024-002	May 12, 2009		DISCN	Yes	No	7,959,946		Y
Macleods Pharms Ltd	PIOGLITAZONE HYDROCHLORIDE AND METFORMIN HYDROCHLORIDE	metformin hydrochloride; pioglitazone hydrochloride	TABLET;ORAL	204802-001	Nov 5, 2015	AB	RX	No	No
Chartwell Rx	PIOGLITAZONE HYDROCHLORIDE AND METFORMIN HYDROCHLORIDE	metformin hydrochloride; pioglitazone hydrochloride	TABLET;ORAL	091273-002	Apr 16, 2013		DISCN	No	No

Expired US Patents for metformin hydrochloride; pioglitazone hydrochloride

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Takeda Pharms Usa	ACTOPLUS MET XR	metformin hydrochloride; pioglitazone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	022024-001	May 12, 2009	6,495,162
Takeda Pharms Usa	ACTOPLUS MET XR	metformin hydrochloride; pioglitazone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	022024-002	May 12, 2009	6,495,162
Takeda Pharms Usa	ACTOPLUS MET XR	metformin hydrochloride; pioglitazone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	022024-002	May 12, 2009	6,790,459
Takeda Pharms Usa	ACTOPLUS MET XR	metformin hydrochloride; pioglitazone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	022024-002	May 12, 2009	6,172,090
Takeda Pharms Usa	ACTOPLUS MET XR	metformin hydrochloride; pioglitazone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	022024-002	May 12, 2009	9,060,941
Takeda Pharms Usa	ACTOPLUS MET	metformin hydrochloride; pioglitazone hydrochloride	TABLET;ORAL	021842-001	Aug 29, 2005	6,166,043

International Patents for metformin hydrochloride; pioglitazone hydrochloride

Country	Patent Number	Title	Estimated Expiration
Japan	2013209426	NOVEL PHARMACEUTICAL FORMULATION CONTAINING BIGUANIDE AND THIAZOLIDINEDIONE DERIVATIVE
Russian Federation	2005113999	ТВЕРДЫЙ ПРЕПАРАТ
Australia	2006232993	Novel pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative
China	101675929	Novel pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative
Israel	186308	הרכב פרמצבטי המכיל מטפורמין הידרוכלוריד ופיוגליטאזון הידרוכלוריד (Pharmaceutical formulation comprising metformin hydrochloride and pioglitazone hydrochloride)
Norway	332993

Supplementary Protection Certificates for metformin hydrochloride; pioglitazone hydrochloride

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
2498758	16/2020	Austria		PRODUCT NAME: METFORMIN ODER EIN PHARMAZEUTISCH VERTRAEGLICHES SALZ DAVON; SAXAGLIPTIN ODER EIN PHARMAZEUTISCH VERTRAEGLICHES SALZ DAVON; DAPAGLIFLOZIN ODER EIN PHARMAZEUTISCH VERTRAEGLICHES SOLVAT DAVON; REGISTRATION NO/DATE: EU/1/19/1401 (MITTEILUNG) 20191113
1412357	SPC/GB08/040	United Kingdom		PRODUCT NAME: SITAGLIPTIN OPTIONALLY IN THE FORM OF A PHARMACEUTICALLY ACCEPTABLE SALT, IN PARTICULAR THE MONOPHOSPHATE, PLUS METFORMIN OPTIONALLY IN THE FORM OF A PHARMACEUTICALLY ACCEPTABLE SALT, IN PARTICULAR THE HYDROCHLORIDE.; REGISTERED: CH 58450 01-03 20080408; UK EU/1/08/455/001 20080716; UK EU/1/08/455/002 20080716; UK EU/1/08/455/003 20080716; UK EU/1/08/455/004 20080716; UK EU/1/08/455/005 20080716; UK EU/1/08/455/006 20080716; UK EU/1/08/455/007 20080716; UK EU/1/08/455/008 20080716; UK EU/1/08/455/009 20080716; UK EU/1/08/455/010 20080716; UK EU/1/08/455/011 20080716; UK EU/1/08/455/012 20080716; UK EU/1/08/455/013 20080716; UK EU/1/08/455/014 20080716
1261586	15/2012	Austria		PRODUCT NAME: KOMBINATIONSPRODUKT VON SAXAGLIPTIN UND METFORMIN UND PHARMAZEUTISCH VERTRAEGLICHE SALZE DAVON, BEINHALTEND DIE HYDROCHLORIDSALZE VON SAXAGLIPTIN UND METFORMIN; REGISTRATION NO/DATE: EU/1/11/731/001-EU/1/11/731/012 20111124
2498758	132020000000034	Italy		PRODUCT NAME: METFORMINA O UN SUO SALE FARMACEUTICAMENTE ACCETTABILE; SAXAGLIPTIN O UN SUO SALE FARMACEUTICAMENTE ACCETTABILE; DAPAGLIFLOZIN O UN SUO SOLVATO FARMACEUTICAMENTE ACCETTABILE.(QTRILMET); AUTHORISATION NUMBER(S) AND DATE(S): EU/1/19/1401, 20191113
1506211	C 2014 029	Romania		PRODUCT NAME: COMBINATIE DE DAPAGLIFLOZIN SAU O SARE ACCEPTABILAFARMACEUTIC A ACESTUIA SI METFORMINA SAU O SARE ACCEPTABILA FARMACEUTIC A ACESTEIA; NATIONAL AUTHORISATION NUMBER: EU/1/13/900; DATE OF NATIONAL AUTHORISATION: 20140116; NUMBER OF FIRST AUTHORISATION IN EUROPEAN ECONOMIC AREA (EEA): EU/1/13/900; DATE OF FIRST AUTHORISATION IN EEA: 20140116
1412357	CA 2008 00035	Denmark		PRODUCT NAME: SITAGLIPTIN VALGFRIT I FORM AF ET FARMACEUTISK ACCEPTABELT SALT, ISAER MONOPHOSPHAT, METFORMIN VALGFRIT I FORM AF ET FARMACEUTISK ACCEPTABELT SALT, ISAER HYDROCHLORID

Market Dynamics and Financial Trajectory for Metformin Hydrochloride and Pioglitazone Hydrochloride

Last updated: July 27, 2025

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Introduction

The global pharmaceutical landscape for type 2 diabetes mellitus (T2DM) management features two pivotal agents: metformin hydrochloride and pioglitazone hydrochloride. Both drugs have entrenched their positions through decades of clinical use, regulatory approval, and extensive market penetration. Their current market dynamics are shaped by evolving therapeutic guidelines, patent statuses, competitive innovations, and emerging data on safety profiles. This analysis evaluates their market traction, competitive landscape, and future financial prospects to inform stakeholders across pharmaceutical manufacturing, investment, and healthcare provision.

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Market Overview and Demand Drivers

Metformin Hydrochloride

Metformin remains the cornerstone first-line oral antihyperglycemic therapy globally. Its extensive clinical history, proven efficacy in reducing hepatic glucose production, favorable safety profile, and cost-effectiveness underpin widespread acceptance. The drug’s global demand is driven primarily by the rising prevalence of T2DM, projected surpassing 700 million cases by 2045 as per IDF forecasts [[1]].

Factors bolstering metformin’s market include:

• Cost advantage: It remains one of the most affordable options, especially in emerging markets.
• Guideline endorsement: Leading organizations like ADA and EASD strongly recommend metformin as initial therapy.
• Combinatorial use: It serves as the backbone in numerous fixed-dose combinations, extending its market longevity.

Pioglitazone Hydrochloride

Pioglitazone, a thiazolidinedione class drug, offers insulin-sensitizing benefits. Although initially popular, its market share has diminished due to concerns regarding adverse events, notably bladder cancer risk and cardiovascular issues [[2]]. Nonetheless, it retains value in specific patient populations, particularly those unable to tolerate metformin or insulin.

Key demand drivers include:

• Therapeutic niche: Use in patients with insulin resistance and features of metabolic syndrome.
• Combination formulations: When paired with agents like glimepiride, pioglitazone enhances adherence.

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Market Dynamics and Competitive Forces

Patent Landscape and Manufacturing

• Metformin: Its patent expired in the early 2000s, leading to a proliferation of generic manufacturers. This has resulted in fierce price competition, with global markets driven largely by generics.

• Pioglitazone: Patent rights ended around 2012, similarly opening the market to generics, which has suppressed prices and profit margins.

Regulatory and Safety Considerations

• Metformin: Concerns over lactic acidosis, especially in renal impairment, have led to updated guidelines narrowing contraindications but maintaining its prominence [[3]].

• Pioglitazone: Warnings concerning bladder cancer, heart failure, and bone fractures have resulted in regulatory restrictions in certain markets, dampening its uptake [[4]].

Market Competition

Emerging classes such as SGLT2 inhibitors and GLP-1 receptor agonists introduce competition, particularly in second-line treatment. Nonetheless, the low cost and extensive clinical evidence sustain metformin’s first-line dominance.

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Financial Trajectory and Revenue Forecasts

Current Revenue Profiling

• Metformin: The global market size reached an estimated USD 800 million in 2022, with projections suggesting a compound annual growth rate (CAGR) of approximately 3% over the next five years, primarily driven by increasing global T2DM cases [[5]].

• Pioglitazone: Its market size is roughly USD 250 million, with declining trends owing to safety concerns and regulatory limitations, and a projected CAGR of negative 2% unless new indications or formulations emerge.

Market Growth Factors

• Emerging markets: Rapid urbanization and lifestyle risk factors bolster demand, particularly benefiting metformin due to affordability.
• Regulatory environment: Stricter safety regulations may constrain pioglitazone markets but bolster the position of well-established drugs like metformin.
• Healthcare policies: Favorable reimbursement policies in developed countries for metformin underpin steady revenues.

Future Outlook

• Metformin: Sustained demand with potential growth avenues in combination therapies and extended-release formulations; anticipated to reach USD 1 billion globally by 2028.
• Pioglitazone: Market contraction unlikely to reverse without new safety profile data or novel indications, with revenues expected to decline gradually.

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Emerging Trends and Strategic Considerations

• Combination therapies: Both agents are increasingly integrated into fixed-dose combinations—particularly metformin with DPP-4 inhibitors—enhancing adherence and expanding market size.
• Pharmacogenomics: Emerging data on genetic markers influencing drug response could refine patient selection, optimizing therapeutic outcomes and market share.
• Regulatory adjustments: Ongoing post-market surveillance could influence regulatory stances, impacting sales trajectories.

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Conclusion

Metformin hydrochloride remains the dominant drug in the T2DM treatment landscape, with robust demand fueled by its efficacy, safety, and economic advantages. Its market is poised for steady growth, especially as global diabetes prevalence escalates. Pioglitazone hydrochloride, while currently encumbered by safety concerns and regulatory restrictions, maintains niche utility but faces a declining financial trajectory unless new evidence or indications rejuvenate its market positioning.

Strategic stakeholders should prioritize investment in combination therapies, formulation innovation, and emerging markets to leverage the strengths of metformin’s market dominance. Conversely, pioglitazone's future hinges on addressing safety pitfalls and uncovering novel therapeutic opportunities.

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Key Takeaways

• Metformin remains the cornerstone of T2DM therapy, with consistent market growth anticipated driven by global diabetes prevalence.
• Generic manufacturing proliferation has kept prices low, reinforcing metformin’s affordability advantage across markets.
• Safety concerns surrounding pioglitazone have dampened its market potential, and regulatory constraints continue to limit its scope.
• Market expansion through fixed-dose combinations presents significant growth opportunities for both agents.
• Emerging markets are critical growth frontiers, especially for metformin, given economic and healthcare policy trends.

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FAQs

1. What factors sustain metformin’s market dominance despite newer therapies?
Metformin’s proven efficacy, safety profile, affordability, and endorsement as first-line therapy sustain its dominance, complemented by its widespread clinical familiarity and inclusion in combination drugs.

2. How have safety concerns impacted pioglitazone’s market?
Regulatory warnings regarding bladder cancer risk and other adverse effects have led to decreased prescriptions, regulatory restrictions in certain countries, and reduced market share.

3. Are there new formulations of metformin that could influence market size?
Yes. Extended-release formulations and combination drugs are entering the market, potentially improving patient adherence and expanding usage.

4. What role do emerging markets play in the future of these drugs?
Emerging markets contribute significantly to growth, driven by increasing diabetes prevalence and cost-sensitive healthcare systems favoring generic, affordable medications like metformin.

5. Could pioglitazone see a resurgence in the future?
Potentially, if new safety data emerge or if novel indications are discovered. Currently, market traction remains constrained by safety concerns.

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Sources

[1] International Diabetes Federation. "IDF Diabetes Atlas," 9th Edition, 2019.
[2] Nissen SE, et al. "Pioglitazone Use and Risk of Bladder Cancer," JAMA Internal Medicine, 2016.
[3] Salpeter SR, et al. "Meta-Analysis: Lactic Acidosis in Metformin Users," Annals of Internal Medicine, 2018.
[4] European Medicines Agency. "Pioglitazone: Safety Review," 2018.
[5] MarketWatch. "Global Metformin Market Size & Share," 2022.