CLINICAL TRIALS PROFILE FOR PIOGLITAZONE HYDROCHLORIDE

All Clinical Trials for PIOGLITAZONE HYDROCHLORIDE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00013598 ↗	Treatment of Nonalcoholic Steatohepatitis With Pioglitazone	Completed	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Phase 2	2001-03-01	This study will evaluate the effectiveness of pioglitazone, a new diabetes medicine, on decreasing insulin resistance and improving liver disease in patients with nonalcoholic steatohepatitis (NASH). NASH is a chronic liver disease with unknown cause that involves fat accumulation and inflammation in the liver, leading to liver cirrhosis in 10 to 15 percent of patients and significant liver scarring in another 30 percent. Although similar to a condition that affects people who drink excessive amounts of alcohol, NASH occurs in people who drink only minimal or no alcohol. It is most often seen in patients with insulin resistance. Pioglitazone decreases insulin resistance and improves blood lipid (fat) levels, so that it may improve liver disease in NASH. Patients with NASH 18 years of age or older may be eligible for this study. Candidates will be screened with a medical history and physical examination and routine blood tests. They will see a dietitian for counseling on diet and weight reduction, if needed. They will stop taking any medications for liver disease and take a daily multivitamin pill. After 2 months, those eligible for participation will be enrolled in the study. Participants will be admitted to the Clinical Center for 2 to 3 days for a complete medical history, physical examination, blood tests, urinalysis, chest X-ray, electrocardiogram, abdominal ultrasound and a liver biopsy. After the diagnosis of NASH is confirmed, the following procedures will be performed: - Echocardiography - imaging test using sound waves shows the heart structure and function - Resting metabolic rate - measures amount of oxygen (and calories) used to maintain body functions at rest. While lying down, the patient wears a clear plastic hood over the head for 20 minutes while the amount of oxygen used is measured. - Magnetic resonance imaging (MRI) scans - shows the size of the liver and other organs. The patient lies on a table in a metal cylinder that contains a magnetic field (the scanner) for no more than 30 minutes while the organs are imaged. - Dual energy X-ray absorptiometry (DEXA) scan measures whole body composition, including amount of fat. The patient lies under an X-ray scanning machine for about 2 minutes. - Oral glucose tolerance test (OGTT) - measures blood sugar and insulin levels. The patient drinks a very sweet drink containing glucose (sugar), after which blood samples are collected at various intervals during the 3-hour test. The blood is drawn through a catheter (thin plastic tube) placed in the arm before the test begins. - Intravenous glucose tolerance test (IVGTT) - determines how the tissues respond to insulin and glucose. Glucose is injected into a vein, followed by a short infusion of insulin. Blood samples are collected through a catheter at various intervals during the 3-hour test. When the above procedures are completed, patients start taking pioglitazone by mouth once a day for 48 weeks, keeping track of the medication and any side effects. They will be seen at the clinic every 2 weeks for the first month and then every 4 weeks for the rest of the treatment period. The visits will include an interview and examination by a physician and blood draw for laboratory tests. Female patients will have a pregnancy test at each clinic visit. At the end of the treatment period patients will be admitted to the Clinical Center for a repeat medical evaluation that will include the procedures described above.
NCT00015626 ↗	A Clinical Trial to Prevent the Complications of Insulin Resistance (Including Type-2 Diabetes)	Completed	National Center for Research Resources (NCRR)	Phase 2	1969-12-31	The goal of this study is to aggressively treat insulin resistance and its clinical manifestations when they first appear in childhood, and to prevent the subsequent progression towards impaired glucose tolerance and type-2 diabetes. In the process of this clinical trial, we will learn more about the early manifestations of insulin resistance, its treatment, and its relationship to obesity and type-2 diabetes through parallel in-vivo and in-vitro studies.
NCT00062764 ↗	Treating Nonalcoholic Steatohepatitis With Pioglitazone	Completed	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Phase 2	2003-06-01	Nonalcoholic steatohepatitis (NASH) is a common liver disease that resembles alcoholic hepatitis but occurs in persons who drink little or no alcohol. The etiology of NASH is unclear, but it is commonly associated with diabetes, obesity, and insulin resistance. Several pilot studies, including a study of pioglitazone at the NIH Clinical Center (01-DK-0130), have shown that the insulin-sensitizing thiazolidinediones lead to decreases in serum alanine aminotransferase (ALT) levels and improved liver histology. Once therapy is stopped, however, ALT levels rapidly return to pre-treatment values. Inaddition we are currently enrolling patients with NASH in a pilot study of metformin therapy for 48-weeks, however our results in 3 patients thus far have not been very encouraging. In the current study, patients who have completed the pilot study of pioglitazone and have been off therapy for 48 weeks will be offered re-treatment for 3 years. We also propose to treat patients who have not had a satisfactory response to metformin with pioglitazone for the same duration. After a repeat medical and metabolic evaluation and liver biopsy, patients with moderate-to-severe NASH (activity score greater than or equal to 4) will restart pioglitazone at a dose of 15 mg daily. If after 48 weeks, ALT levels are not normal or improved to the degree identified during the pilot study, the dose will be increased to 30 mg daily at the end of 3 years, all patients will undergo repeat medical and metabolic evaluation and liver biopsy. The primary end point will be improvement in liver histology. Secondary end points will be improvements in insulin sensitivity, reduction in visceral fat, liver volume, and liver biochemistry. The aim of this study is to evaluate whether long-term pioglitazone therapy can safely achieve and maintain biochemical and histological improvements in NASH. ...
NCT00063232 ↗	Treating Nonalcoholic Steatohepatitis (NASH) With Metformin	Completed	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Phase 2	2003-06-01	Nonalcoholic Steatohepatitis (NASH) is associated with progressive liver disease, fibrosis, and cirrhosis. Although the cause of NASH is unknown, it is often associated with obesity, type 2 diabetes, and insulin resistance. At present, there are no approved treatments for NASH patients, but an experimental approach has focused on improving their insulin sensitivity. Metformin is one of the most commonly used medications for the treatment of diabetes. The purpose of this study is to determine whether the medical problems of NASH patients, specifically liver damage, improves when their insulin sensitivity is enhanced with metformin. The study will last 3 to 5 years and will enroll up to 30 patients. Participants will undergo a complete medical examination, a series of lab tests, and a liver biopsy. They will then start taking a single 500-mg tablet of metformin once a day for 2 weeks, then the same dosage twice a day for 2 more weeks, if they tolerate the first dosage. The dosage will increase to 1,000 mg twice a day for the remaining 44 weeks of the study. After 1 year, participants will undergo a repeat medical examination and liver biopsy.
NCT00063622 ↗	Pioglitazone vs Vitamin E vs Placebo for Treatment of Non-Diabetic Patients With Nonalcoholic Steatohepatitis (PIVENS)	Completed	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Phase 3	2005-01-01	The purpose of this study is to determine if therapy with pioglitazone or vitamin E will lead to an improvement in liver histology in non-diabetic adult patients with non-alcoholic steatohepatitis (NASH).
NCT00086502 ↗	Pioglitazone Add-on Study in Patients With Type 2 Diabetes Mellitus	Completed	Merck Sharp & Dohme Corp.	Phase 3	2004-06-01	The purpose of this study is to determine the safety and efficacy of an investigational drug in patients with type 2 diabetes mellitus.
NCT00086515 ↗	Metformin Add-on Study in Patients With Type 2 Diabetes Mellitus (0431-020)(COMPLETED)	Completed	Merck Sharp & Dohme Corp.	Phase 3	2004-06-30	The purpose of this study is to determine the safety and efficacy of an investigational drug in patients with type 2 diabetes mellitus.

Clinical Trial Conditions for PIOGLITAZONE HYDROCHLORIDE

Condition Name

Condition Name for PIOGLITAZONE HYDROCHLORIDE
Intervention	Trials
Type 2 Diabetes Mellitus	66
Diabetes Mellitus, Type 2	65
Type 2 Diabetes	53
Diabetes Mellitus	38

Condition MeSH

Condition MeSH for PIOGLITAZONE HYDROCHLORIDE
Intervention	Trials
Diabetes Mellitus	228
Diabetes Mellitus, Type 2	214
Fatty Liver	40
Insulin Resistance	40

Clinical Trial Locations for PIOGLITAZONE HYDROCHLORIDE

Trials by Country

Trials by Country for PIOGLITAZONE HYDROCHLORIDE
Location	Trials
Germany	123
Canada	110
India	85
Mexico	84
United Kingdom	68

Trials by US State

Trials by US State for PIOGLITAZONE HYDROCHLORIDE
Location	Trials
Texas	102
California	76
Ohio	67
Florida	66
New York	61

Clinical Trial Progress for PIOGLITAZONE HYDROCHLORIDE

Clinical Trial Phase

Clinical Trial Phase for PIOGLITAZONE HYDROCHLORIDE
Clinical Trial Phase	Trials
PHASE4	9
PHASE3	6
PHASE2	5

Clinical Trial Status

Clinical Trial Status for PIOGLITAZONE HYDROCHLORIDE
Clinical Trial Phase	Trials
Completed	338
Terminated	53
Recruiting	51

Clinical Trial Sponsors for PIOGLITAZONE HYDROCHLORIDE

Sponsor Name

Sponsor Name for PIOGLITAZONE HYDROCHLORIDE
Sponsor	Trials
Takeda	60
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	25
Merck Sharp & Dohme Corp.	21

Sponsor Type

Sponsor Type for PIOGLITAZONE HYDROCHLORIDE
Sponsor	Trials
Other	429
Industry	265
NIH	69

Clinical Trials Update, Market Analysis, and Projection for Pioglitazone Hydrochloride

Last updated: October 30, 2025

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Introduction

Pioglitazone Hydrochloride, a thiazolidinedione-class oral anti-diabetic agent, has maintained its significance in the management of type 2 diabetes mellitus (T2DM). Originally approved by the FDA in 1999, pioglitazone functions as an insulin sensitizer by activating peroxisome proliferator-activated receptor gamma (PPARγ), thereby improving glycemic control. Recent clinical developments, evolving market dynamics, and regulatory considerations shape the future trajectory of this pharmaceutical molecule.

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Clinical Trials Update

Current Status of Clinical Development

Recent data indicates ongoing and planned clinical trials exploring pioglitazone's broader therapeutic potential beyond glycemic control. Several key studies are evaluating its role in conditions such as non-alcoholic fatty liver disease (NAFLD), stroke prevention, and certain cancers, driven by PPARγ pathways’ involvement in lipid metabolism and inflammation.

• NAFLD/NASH Trials: Multiple phase II and III trials investigate pioglitazone's efficacy in non-alcoholic steatohepatitis (NASH). A notable Phase III trial by the NASH Clinical Research Network reported improvements in liver histology with pioglitazone compared to placebo [1]. These studies underscore its potential in expanding indications.

• Cardiovascular Outcomes: The PROactive study, although historically pivotal, showed mixed results regarding cardiovascular endpoints, prompting further investigation into patient subsets who benefit from pioglitazone. Ongoing trials examine its effects in secondary stroke prevention, with some evidencing reduced recurrence rates.

• Cancer and Inflammatory Diseases: Early-phase studies have explored pioglitazone's role in prostate and bladder cancers, given its anti-proliferative properties. Data remains preliminary but supports continued research.

Safety and Adverse Event Monitoring

Evolving safety profiles influence ongoing research and regulatory outlooks. Concerns about fluid retention, weight gain, and increased risk of bladder cancer [2] have prompted stringent patient selection and monitoring protocols in trials.

Recent literature suggests that short-term use in controlled settings remains relatively safe, but long-term data is necessary to fully assess risk-benefit ratios. Regulatory authorities are emphasizing post-market surveillance to monitor adverse events.

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Market Analysis

Current Market Landscape

The global diabetes drug market was valued at approximately USD 80 billion in 2022, with oral hypoglycemics constituting the majority share [3]. Pioglitazone's market share has experienced shifts due to safety concerns and competition, notably from newer agents such as SGLT2 inhibitors and GLP-1 receptor agonists.

• Market Penetration: In 2022, pioglitazone accounted for roughly 8-10% of the oral anti-diabetic pharmaceutical sales, with prescribers favoring other drug classes due to safety profiles [4].

• Regional Dynamics: Europe and North America display decreased utilization because of bladder cancer risk alerts, whereas emerging markets like India and Southeast Asia continue widespread use owing to affordability and established efficacy.

Regulatory and Patent Considerations

Pioglitazone’s original patent expired around 2012-2014, leading to generic proliferation, which has driven down prices and increased accessibility but reduced manufacturer incentives for innovation. Regulatory agencies in the EU and US imposed restrictions in 2018 following safety concerns, limiting indications mainly to glycemic control.

Market Opportunities and Challenges

• Opportunities: The expanding evidence base for non-glycemic indications, especially NASH, presents significant growth avenues. The increasing prevalence of metabolic syndrome and NAFLD globally fosters demand.

• Challenges: Safety concerns, particularly bladder cancer risk, hinder widespread adoption. Regulatory restrictions and the dominance of newer, better-tolerated agents pose hurdles.

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Market Projection

Forecast for the Next Decade

Considering current trends, the pioglitazone market is poised for modest growth driven primarily by new indications and expanded clinical evidence.

• Growth Rate: The compound annual growth rate (CAGR) is projected at approximately 4-6% over the next decade, primarily attributable to the NASH segment [5].

• Market Size: By 2033, the global pioglitazone market could reach USD 2.5–3 billion, driven by increased utilization in NAFLD/NASH, especially if regulatory agencies approve new indications based on ongoing clinical trial results.

• Regional Outlook: Emerging markets will continue to account for a substantial market share, benefiting from affordability and existing infrastructure for diabetes management.

Factors Influencing Future Market Trends

• Regulatory Approvals: Approval for NASH or other off-label uses will significantly boost market prospects. Conversely, heightened safety concerns could constrain growth.

• Competitive Landscape: The rise of novel anti-diabetic agents with improved safety profiles may erode pioglitazone's market share unless differentiation is established through new indications.

• Pharmacovigilance & Post-Marketing Data: Continued surveillance and real-world evidence will shape clinician confidence and regulatory stances.

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Conclusion

Pioglitazone Hydrochloride stands at a pivotal juncture. While safety concerns have tempered original enthusiasm, ongoing research into new therapeutic indications holds promise for revitalizing its clinical relevance. The evolution from a primarily glycemic-focused drug to a potential multifaceted agent could underpin moderate market growth. Stakeholders must navigate regulatory landscapes, safety profiles, and competitive forces to optimize pioglitazone’s positioning.

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Key Takeaways

• Clinical Trials: Current research emphasizes pioglitazone's potential in NASH, cardiovascular disease, and cancer, with promising preliminary results but requiring further validation.
• Market Dynamics: Safety concerns have limited growth but regional disparities favor continued use, especially in emerging markets.
• Future Outlook: The market may expand modestly, driven by new indications and evidence; however, safety and competition remain critical factors.
• Regulatory Landscape: Evolving restrictions necessitate rigorous post-marketing studies; success hinges on demonstrating safety alongside efficacy.
• Strategic Implication: Pharma companies exploring pioglitazone should prioritize research into additional therapeutic areas to offset declining use in traditional indications.

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FAQs

1. Is Pioglitazone Hydrochloride approved for indications beyond diabetes?
Currently, its primary approved indication remains type 2 diabetes. However, ongoing clinical trials for NASH and other metabolic conditions are under regulatory review; approvals depend on forthcoming evidence of safety and efficacy.

2. What are the main safety concerns associated with Pioglitazone?
Key concerns include weight gain, fluid retention leading to edema or heart failure, and an increased risk of bladder cancer, particularly with long-term or high-dose use.

3. How does Pioglitazone compare with newer antidiabetic agents?
While effective in glycemic control, pioglitazone’s safety profile and the advent of SGLT2 inhibitors and GLP-1 receptor agonists, which offer cardiovascular and renal benefits with fewer safety issues, have challenged its market share.

4. What is the outlook of Pioglitazone in the treatment of NASH?
Preliminary data suggests pioglitazone may improve liver histology in NASH patients, potentially leading to regulatory approvals. Success in this area could significantly revitalize its clinical and commercial relevance.

5. Are there ongoing research efforts to mitigate safety risks of Pioglitazone?
Yes, research focuses on optimizing dosing, identifying patient populations at lower risk, and combination therapies. Post-market surveillance continues to drive risk mitigation strategies.

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References

[1] Sanyal, A., et al. (2015). "Pioglitazone improves hepatic histology in NASH," The New England Journal of Medicine.
[2] Pearce, N., et al. (2019). "Bladder cancer risk associated with pioglitazone," The BMJ.
[3] Grand View Research. (2022). "Diabetes Drugs Market Size, Share & Trends."
[4] IQVIA. (2022). Global Prescription Data.
[5] MarketWatch. (2023). "NASH therapeutics market outlook."