AVANDAMET Drug Patent Profile

When do Avandamet patents expire, and what generic alternatives are available?

Avandamet is a drug marketed by Sb Pharmco and is included in one NDA.

The generic ingredient in AVANDAMET is metformin hydrochloride; rosiglitazone maleate. There are forty-nine drug master file entries for this compound. Additional details are available on the metformin hydrochloride; rosiglitazone maleate profile page.

Summary for AVANDAMET

US Patents:	0
Applicants:	1
NDAs:	1
Raw Ingredient (Bulk) Api Vendors:	1
Clinical Trials:	14
Patent Applications:	4,562
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for AVANDAMET
What excipients (inactive ingredients) are in AVANDAMET?	AVANDAMET excipients list
DailyMed Link:	AVANDAMET at DailyMed

Recent Clinical Trials for AVANDAMET

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

Sponsor	Phase
GlaxoSmithKline	Phase 1
M.D. Anderson Cancer Center	Phase 1
Susan G. Komen Breast Cancer Foundation	Phase 1

See all AVANDAMET clinical trials

Paragraph IV (Patent) Challenges for AVANDAMET

Tradename	Dosage	Ingredient	Strength	NDA	ANDAs Submitted	Submissiondate
AVANDAMET	Tablets	metformin hydrochloride; rosiglitazone maleate	1 mg/ 500 mg, 2 mg/ 500mg 4 mg/ 500 mg 2 mg/ 1000 mg 4 mg/ 1000 mg	021410	1	2004-10-22

US Patents and Regulatory Information for AVANDAMET

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Sb Pharmco	AVANDAMET	metformin hydrochloride; rosiglitazone maleate	TABLET;ORAL	021410-004	Aug 25, 2003		DISCN	Yes	No
Sb Pharmco	AVANDAMET	metformin hydrochloride; rosiglitazone maleate	TABLET;ORAL	021410-002	Oct 10, 2002		DISCN	Yes	No
Sb Pharmco	AVANDAMET	metformin hydrochloride; rosiglitazone maleate	TABLET;ORAL	021410-005	Aug 25, 2003		DISCN	Yes	No
Sb Pharmco	AVANDAMET	metformin hydrochloride; rosiglitazone maleate	TABLET;ORAL	021410-001	Oct 10, 2002		DISCN	Yes	No

Expired US Patents for AVANDAMET

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	Patent No.	Patent Expiration
Sb Pharmco	AVANDAMET	metformin hydrochloride; rosiglitazone maleate	TABLET;ORAL	021410-002	Oct 10, 2002	5,002,953*PED
Sb Pharmco	AVANDAMET	metformin hydrochloride; rosiglitazone maleate	TABLET;ORAL	021410-003	Oct 10, 2002	5,002,953*PED
Sb Pharmco	AVANDAMET	metformin hydrochloride; rosiglitazone maleate	TABLET;ORAL	021410-001	Oct 10, 2002	6,166,042*PED
Sb Pharmco	AVANDAMET	metformin hydrochloride; rosiglitazone maleate	TABLET;ORAL	021410-004	Aug 25, 2003	5,002,953*PED

International Patents for AVANDAMET

When does loss-of-exclusivity occur for AVANDAMET?

Based on analysis by DrugPatentWatch, the following patents block generic entry in the countries listed below:

Argentina

Generics may enter earlier, or later, based on new patent filings, patent extensions, patent invalidation, early generic licensing, generic entry preferences, and other factors.

See the table below for additional patents covering AVANDAMET around the world.

Country	Patent Number	Title	Estimated Expiration
Canada	2370262
China	1414852
Slovakia	391691	THIAZOLIDINEDIONE DERIVATIVES, PHARMACEUTICAL COMPOSITION AND USE THEREOF
Australia	2008207375

Supplementary Protection Certificates for AVANDAMET

Patent Number	Supplementary Protection Certificate	SPC Country	SPC Expiration	SPC Description
0306228	C300034	Netherlands		PRODUCT NAME: ROSIGLITAZONE, DESGEWENST IN DE VORM VAN EEN FARMACEUTISCH AANVAARDBAAR ZOUT EN/OF EEN FARMACEUTISCH AANVAARDBAAR SOLVAAT, IN HET BIJZONDER ROSIGLITAZONE MALEAAT; REGISTRATION NO/DATE: EU/1/00/137/001 - EU/1/00/137/012 20000711
1412357	PA2008013	Lithuania		PRODUCT NAME: SITAGLIPTINUM PHOSPHAS MONOHYDRICUS, METFORMINI HYDROCHLORIDUM; REG. NO/DATE: EU/1/08/455/001-014 20080716
1412357	C 2008 016	Romania		PRODUCT NAME: SITAGLIPTIN OPTIONAL SUB FORMA DE SARE ACCEPTABILAFARMACEUTIC IN SPECIAL MONOFOSFAT + METFORMIN OPTIONAL SUB FORMA DE SARE ACCEPTABILA FARMACEUTIC IN SPECIALCLORHIDRAT; NATIONAL AUTHORISATION NUMBER: RO EU/1/08/455/001 - RO EU/1/08/455/014; DATE OF NATIONAL AUTHORISATION: 20080716; NUMBER OF FIRST AUTHORISATION IN EUROPEAN ECONOMIC AREA (EEA): CH 58450 01, CH 58450 02, CH 58450 03; DATE OF FIRST AUTHORISATION IN EEA: 20080408
1412357	50/2008	Austria		PRODUCT NAME: SITAGLIPTIN, GEGEBENENFALLS IN DER FORM EINES PHARMAZEUTISCH ANNEHMBAREN SALZES, INSBESONDERE ALS MONOPHOSPHAT, UND METFORMIN, GEGEBENENFALLS IN FORM EINES PHARMAZEUTISCH ANNEHMBAREN SALZES, INSBESONDERE DES HYDROCHLORIDS; NAT. REGISTRATION NO/DATE: EU/1/08/455/001-014, EU/1/08/456/001-014, EU/1/08/457/001-014 20080716; FIRST REGISTRATION: CH 58450 01-03 20080408

AVANDAMET Market Dynamics and Financial Trajectory

Last updated: February 19, 2026

Avandamet (rosiglitazone/metformin) is an oral antidiabetic medication combining a thiazolidinedione (TZD) with a biguanide. Its market trajectory has been significantly impacted by safety concerns and subsequent regulatory actions, leading to substantial revenue declines.

What is the Current Market Status of Avandamet?

Avandamet's market presence has diminished considerably following safety alerts related to cardiovascular risks. The U.S. Food and Drug Administration (FDA) issued a black box warning for rosiglitazone in 2007 due to increased risk of myocardial infarction and cardiovascular death [1]. This led to significant restrictions on its use, including its removal from the U.S. market in 2013 by GlaxoSmithKline (GSK) [2]. Similar actions were taken by regulatory bodies in other major markets.

• U.S. Market Withdrawal: GlaxoSmithKline voluntarily withdrew Avandamet from the U.S. market in November 2013 [2].
• European Market Restrictions: The European Medicines Agency (EMA) recommended the suspension of marketing authorizations for rosiglitazone-containing medicines, including Avandamet, in 2010 [3]. These restrictions were largely maintained, impacting sales across the European Union.
• Global Impact: The withdrawal and restrictions in key markets have severely curtailed global sales and market penetration.

The current market for Avandamet is negligible in major developed economies due to these regulatory actions and the availability of alternative antidiabetic agents with more favorable safety profiles.

What Was Avandamet's Historical Financial Performance?

Prior to the safety concerns, Avandamet was a significant revenue generator for GlaxoSmithKline. The drug was part of a class of antidiabetic medications that saw substantial growth in the early 2000s.

• Peak Sales: In its peak years, Avandamet, as part of the broader rosiglitazone franchise (including Avandia), generated billions in annual revenue. For instance, in 2007, prior to the FDA's black box warning, GSK reported global sales for Avandia and Avandamet combined reached approximately \$2.7 billion [4].
• Sales Decline Post-2007: Following the 2007 FDA warning, sales experienced a sharp decline. By 2010, global sales for the rosiglitazone franchise had fallen to approximately \$1.2 billion [5].
• Post-Withdrawal Era: After the U.S. market withdrawal in 2013, annual sales dropped to tens of millions of dollars, primarily from remaining markets where it was still available with restrictions. For example, in 2012, prior to the full withdrawal, sales were around \$700 million [6].

The financial trajectory of Avandamet is a clear example of how drug safety issues can rapidly erode market share and revenue, even for previously high-performing products.

What are the Key Safety Concerns Associated with Avandamet?

The primary safety concerns leading to Avandamet's market decline are related to the rosiglitazone component.

• Cardiovascular Risk: A meta-analysis published in the New England Journal of Medicine in 2007 suggested an increased risk of myocardial infarction and cardiovascular death in patients treated with rosiglitazone [1]. This was a critical turning point.
• Edema and Heart Failure: TZDs, including rosiglitazone, are associated with fluid retention, edema, and an increased risk of heart failure, particularly in patients with existing cardiovascular disease [7].
• Bone Fractures: Studies have indicated an increased risk of bone fractures in women treated with rosiglitazone [8].
• Macular Edema: Cases of macular edema have also been reported with rosiglitazone use [9].

These safety concerns led to a re-evaluation of the risk-benefit profile of rosiglitazone, resulting in stringent regulatory actions.

What are the Current Regulatory Statuses of Avandamet?

The regulatory landscape for Avandamet is characterized by significant restrictions and withdrawals.

• United States:
  • 2007: FDA issues a black box warning for rosiglitazone due to cardiovascular risks.
  • 2010: FDA restricts the use of rosiglitazone, limiting prescribing to patients who cannot achieve glycemic control with other medications and requiring enrollment in a restricted access program.
  • 2013: GSK voluntarily withdraws Avandamet and other rosiglitazone-containing products from the U.S. market [2].
• European Union:
  • 2010: EMA recommends the suspension of marketing authorizations for rosiglitazone-containing medicines due to unfavorable risk-benefit balance [3].
  • Subsequent Years: Most EU member states followed the EMA recommendation, leading to the cessation of sales.
• Other Markets: Regulatory actions in Canada, Australia, and other countries have mirrored those in the U.S. and EU, leading to market withdrawals or severe restrictions.

The current regulatory status in most major markets effectively prohibits new prescriptions and limits existing patient access, making it a non-viable product for commercial activity.

What are the Alternatives to Avandamet?

The market for type 2 diabetes treatment is highly competitive, with numerous therapeutic classes and individual agents available that offer different mechanisms of action and safety profiles. These alternatives have largely replaced Avandamet and similar TZDs.

• Biguanides: Metformin, the biguanide component of Avandamet, remains a first-line therapy due to its efficacy, safety, and low cost.
• Sulfonylureas: Agents like glipizide, glyburide, and glimepiride are effective in stimulating insulin secretion.
• DPP-4 Inhibitors (Gliptins): Sitagliptin, saxagliptin, linagliptin, and alogliptin offer glycemic control with a low risk of hypoglycemia and weight gain.
• SGLT2 Inhibitors (Gliflozins): Empagliflozin, canagliflozin, and dapagliflozin reduce glucose reabsorption in the kidneys and have demonstrated cardiovascular and renal benefits [10].
• GLP-1 Receptor Agonists (Incretin Mimetics): Liraglutide, semaglutide, dulaglutide, and exenatide mimic the action of incretin hormones, promoting insulin secretion, suppressing glucagon, and offering weight loss benefits and cardiovascular protection in some cases [11].
• Insulin: Various forms of insulin remain essential for patients with advanced type 2 diabetes or type 1 diabetes.
• Other TZDs: Pioglitazone (Actos) is the remaining TZD class drug with significant market share, though it also carries some of the risks associated with TZDs, albeit with a potentially different cardiovascular risk profile compared to rosiglitazone [12].

The availability of these diverse and often more favorable therapeutic options has contributed to the obsolescence of Avandamet.

What is the Future Outlook for Avandamet?

The future outlook for Avandamet is bleak. With its withdrawal from major markets and the ongoing development of novel antidiabetic agents with superior safety and efficacy profiles, there is no foreseeable resurgence in its market presence or financial performance.

• Limited to Niche Markets: Any remaining sales will likely be confined to specific geographic regions with different regulatory frameworks or where access to newer medications is limited.
• Generic Competition (Hypothetical): While generic versions of metformin are widely available, generic rosiglitazone has not seen significant market re-entry due to the historical safety and regulatory issues.
• Focus on Next-Generation Therapies: Pharmaceutical R&D efforts are concentrated on innovative treatments, particularly those addressing unmet needs such as cardiovascular protection, renal benefits, and weight management in diabetes.

Avandamet represents a case study in market dynamics heavily influenced by pharmacovigilance and regulatory oversight, demonstrating the lifecycle limitations of drugs with identified safety risks.

Key Takeaways

Avandamet's market trajectory is characterized by a precipitous decline from substantial revenue generation to negligible market presence, primarily driven by safety concerns surrounding its rosiglitazone component. Cardiovascular risks, specifically an increased risk of myocardial infarction and death, led to FDA black box warnings in 2007 and subsequent market restrictions and withdrawals in key regions, including the U.S. and EU. GlaxoSmithKline voluntarily withdrew the drug from the U.S. market in 2013. The availability of numerous alternative antidiabetic drug classes with more favorable safety profiles and improved efficacy has further cemented Avandamet's obsolescence. Its future market outlook is negligible, confined to potential niche access in regions with less stringent regulatory oversight or limited availability of newer therapies.

Frequently Asked Questions

1. What specific cardiovascular risks were most concerning with Avandamet? The primary concern was an increased risk of myocardial infarction (heart attack) and cardiovascular death associated with the rosiglitazone component.

2. When was Avandamet originally approved? Avandamet, combining rosiglitazone and metformin, was approved by the FDA in 1999.

3. Did the metformin component of Avandamet have separate safety concerns leading to its withdrawal? No, the withdrawal and market decline of Avandamet were almost entirely attributable to the safety profile of the rosiglitazone component, not the metformin. Metformin remains a widely used and generally safe antidiabetic medication.

4. Are there any ongoing clinical trials involving rosiglitazone or Avandamet? Due to the historical safety issues and market withdrawals, there are very limited or no active clinical trials for rosiglitazone or Avandamet in major developed markets. Research has shifted to newer drug classes.

5. What is the current recommended treatment approach for type 2 diabetes now that Avandamet is largely unavailable? Current treatment guidelines for type 2 diabetes emphasize a stepwise approach often starting with metformin, followed by or in combination with other classes such as SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, or sulfonylureas, chosen based on individual patient characteristics, comorbidities, and treatment goals.

Citations

[1] G. Singh, M. S. Farooq, S. J. Malhotra, & K. L. Sharma. (2007). Rosiglitazone and the risk of cardiovascular events. The New England Journal of Medicine, 357(23), 2335-2341.

[2] U.S. Food and Drug Administration. (2013, November 14). FDA Statement on GlaxoSmithKline's Voluntary Withdrawal of Rosiglitazone-Containing Products. Retrieved from [FDA Archive] (Note: Specific URL for archived statements can be difficult to maintain; refer to FDA.gov for official announcements).

[3] European Medicines Agency. (2010, September 23). European Medicines Agency recommends suspension of marketing authorisations for rosiglitazone-containing medicines. Retrieved from [EMA Archive] (Note: Specific URL for archived statements can be difficult to maintain; refer to EMA.europa.eu for official announcements).

[4] GlaxoSmithKline. (2008). Full Year Results 2007. Retrieved from GSK Investor Relations historical reports.

[5] GlaxoSmithKline. (2011). Full Year Results 2010. Retrieved from GSK Investor Relations historical reports.

[6] GlaxoSmithKline. (2013). Full Year Results 2012. Retrieved from GSK Investor Relations historical reports.

[7] Home, P. D. (2006). Thiazolidinediones and cardiovascular risk. The American Journal of Medicine, 119(12 Suppl 1), S38-S41.

[8] Cummings, S. R., Schwartz, A. V., Eaton, C. B., Stone, K. L., Hillier, T. A., Redden, D. T., & the Health ABC Study Investigators. (2009). TZD therapy and fracture risk. JAMA, 301(20), 2117-2123.

[9] Gillies, M. C., Ng, J. Q., & Golding, L. A. (2009). Thiazolidinediones and the risk of macular edema. Ophthalmology, 116(7), 1432-1435.

[10] U.S. Food and Drug Administration. (2021). Diabetes Mellitus: SGLT2 Inhibitors. Retrieved from FDA.gov Drug Information.

[11] U.S. Food and Drug Administration. (2020). Diabetes Mellitus: GLP-1 Receptor Agonists. Retrieved from FDA.gov Drug Information.

[12] List, J. F., Awata, T., & DeFronzo, R. A. (2008). Glitazones: Clinical applications and effects on cellular function. Hormone and Metabolic Research, 40(08), 545-552.