CLINICAL TRIALS PROFILE FOR PIOGLITAZONE HYDROCHLORIDE AND GLIMEPIRIDE

All Clinical Trials for Pioglitazone Hydrochloride And Glimepiride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00225264 ↗	Efficacy Study of Pioglitazone and Glimepiride on the Rate of Progression of Atherosclerotic Disease.	Completed	Takeda	Phase 3	2003-10-01	The primary purpose of this study is to compare the effects of pioglitazone, once daily (QD), versus glimepiride on the amount of thickening of the carotid artery.
NCT00225277 ↗	Efficacy Study of Pioglitazone Compared to Glimepiride on Coronary Atherosclerotic Disease Progression in Subjects With Type 2 Diabetes Mellitus	Completed	Takeda	Phase 3	2003-07-01	The purpose of this study was to determine the efficacy of pioglitazone, once daily (QD), compared to glimepiride on atherosclerotic disease measured by intravascular ultrasound.
NCT00576784 ↗	Metabolic Effects of Pioglitazone in Type II Diabetic Patients Previously Treated With Insulin	Completed	IKFE Institute for Clinical Research and Development	Phase 4	2005-04-01	The goal of the study is to demonstrate whether a switch from insulin therapy to an oral therapy with pioglitazone/glimepiride will lead to a deterioration of glycemic control (increase in HbA1c by more than 0.5 %) within a 6 month observation period.
NCT00700856 ↗	Thiazolidinediones Or Sulphonylureas and Cardiovascular Accidents.Intervention Trial	Unknown status	Associazione Medici Diabetologi (AMD)	Phase 4	2008-09-01	Background: In patients with type 2 diabetes inadequately controlled with metformin, two main therapeutic options are equally plausible: add-on a sulfonylurea (SU) or a thiazolidinedione (TZD). Since the two classes of drugs clearly differ in terms of mechanisms of action, side effects, economic costs and cardiovascular risk factors profile, a direct comparison of the two therapeutic strategies would be most appropriate. Aims: 1) To evaluate the effects of add-on pioglitazone as compared with add-on a SU on the incidence of cardiovascular events in type 2 diabetic patients inadequately controlled with metformin; 2) To compare the two treatments in terms of glycemic control, safety, and economic costs. Methods: multicentre, randomised, open label, parallel group trial of 48 months duration. Eligible participants (type 2 diabetic males and females, aged 50-75 years, BMI 20-45 Kg/m2, in treatment for the last two months with metformin 2 gr/die in monotherapy and with HbA1c > =7.0% and <= 9.0%) will be randomized to add-on: a SU - glibenclamide (5-15 mg/die), gliclazide (30-120 mg/die), glimepiride (2-6 mg/die), chosen according to local practice - or pioglitazone (15-45 mg/die). A HbA1c value > 8.0 % on two consecutive occasions will lead to addition of insulin to ongoing oral therapy. Primary efficacy outcome: a composite endpoint of all-cause mortality, non fatal MI (including silent MI), non fatal stroke, and unplanned coronary revascularization. Secondary outcomes. Principal secondary outcome: a composite ischemic endpoint of sudden death, fatal and non fatal acute MI (including silent MI), fatal and non fatal stroke, major amputations (above ankle), endovascular or surgical intervention on the coronary, leg or carotid arteries. Other secondary outcomes - a composite cardiovascular end point including the primary end point plus hospitalization for heart failure, endovascular or surgical intervention on the coronary, leg or carotid arteries, silent MI, angina - by WHO criteria and confirmed by a new electrocardiogram abnormality - intermittent claudication with an ankle/brachial index lower than 090; events of heart failure; a microvascular endpoint including: plasma creatinine increase of 2 times above the baseline value or creatinine clearance reduction of 20ml/min/1. 73m2 or development of overt nephropathy (dialysis or plasma creatinine >3,3 mg/dl) or macroalbuminuria; glycemic control (changes from baseline in HBA1c, time to failure of glycemic control, i.e., HBA1c >8.0% on two consecutive occasions three months apart); major CV risk factors (lipids, blood pressure, microalbuminuria, inflammation markers, waist circumference); safety and side effects; direct and indirect costs. Data regarding CV endpoints, safety, tolerability, and study conduct will be monitored and analyzed by an independent committee, and will be not available to the study investigators until the closing of data collection. Efficacy end points will be analyzed on an intention-to-treat basis.
NCT00700856 ↗	Thiazolidinediones Or Sulphonylureas and Cardiovascular Accidents.Intervention Trial	Unknown status	Associazione Nazionale Medici Cardiologi Ospedalieri	Phase 4	2008-09-01	Background: In patients with type 2 diabetes inadequately controlled with metformin, two main therapeutic options are equally plausible: add-on a sulfonylurea (SU) or a thiazolidinedione (TZD). Since the two classes of drugs clearly differ in terms of mechanisms of action, side effects, economic costs and cardiovascular risk factors profile, a direct comparison of the two therapeutic strategies would be most appropriate. Aims: 1) To evaluate the effects of add-on pioglitazone as compared with add-on a SU on the incidence of cardiovascular events in type 2 diabetic patients inadequately controlled with metformin; 2) To compare the two treatments in terms of glycemic control, safety, and economic costs. Methods: multicentre, randomised, open label, parallel group trial of 48 months duration. Eligible participants (type 2 diabetic males and females, aged 50-75 years, BMI 20-45 Kg/m2, in treatment for the last two months with metformin 2 gr/die in monotherapy and with HbA1c > =7.0% and <= 9.0%) will be randomized to add-on: a SU - glibenclamide (5-15 mg/die), gliclazide (30-120 mg/die), glimepiride (2-6 mg/die), chosen according to local practice - or pioglitazone (15-45 mg/die). A HbA1c value > 8.0 % on two consecutive occasions will lead to addition of insulin to ongoing oral therapy. Primary efficacy outcome: a composite endpoint of all-cause mortality, non fatal MI (including silent MI), non fatal stroke, and unplanned coronary revascularization. Secondary outcomes. Principal secondary outcome: a composite ischemic endpoint of sudden death, fatal and non fatal acute MI (including silent MI), fatal and non fatal stroke, major amputations (above ankle), endovascular or surgical intervention on the coronary, leg or carotid arteries. Other secondary outcomes - a composite cardiovascular end point including the primary end point plus hospitalization for heart failure, endovascular or surgical intervention on the coronary, leg or carotid arteries, silent MI, angina - by WHO criteria and confirmed by a new electrocardiogram abnormality - intermittent claudication with an ankle/brachial index lower than 090; events of heart failure; a microvascular endpoint including: plasma creatinine increase of 2 times above the baseline value or creatinine clearance reduction of 20ml/min/1. 73m2 or development of overt nephropathy (dialysis or plasma creatinine >3,3 mg/dl) or macroalbuminuria; glycemic control (changes from baseline in HBA1c, time to failure of glycemic control, i.e., HBA1c >8.0% on two consecutive occasions three months apart); major CV risk factors (lipids, blood pressure, microalbuminuria, inflammation markers, waist circumference); safety and side effects; direct and indirect costs. Data regarding CV endpoints, safety, tolerability, and study conduct will be monitored and analyzed by an independent committee, and will be not available to the study investigators until the closing of data collection. Efficacy end points will be analyzed on an intention-to-treat basis.

Clinical Trial Conditions for Pioglitazone Hydrochloride And Glimepiride

Condition Name

Condition Name for Pioglitazone Hydrochloride And Glimepiride
Intervention	Trials
Type 2 Diabetes Mellitus	6
Type 2 Diabetes	4
Diabetes Mellitus	4
Diabetes Mellitus, Type 2	4

Condition MeSH

Condition MeSH for Pioglitazone Hydrochloride And Glimepiride
Intervention	Trials
Diabetes Mellitus, Type 2	15
Diabetes Mellitus	15
Insulin Resistance	2
Fatty Liver	1

Clinical Trial Locations for Pioglitazone Hydrochloride And Glimepiride

Trials by Country

Trials by Country for Pioglitazone Hydrochloride And Glimepiride
Location	Trials
United States	127
Germany	32
Canada	12
Italy	10
United Kingdom	4

Trials by US State

Trials by US State for Pioglitazone Hydrochloride And Glimepiride
Location	Trials
Louisiana	4
Florida	4
California	4
Arizona	4
Alabama	4

Clinical Trial Progress for Pioglitazone Hydrochloride And Glimepiride

Clinical Trial Phase

Clinical Trial Phase for Pioglitazone Hydrochloride And Glimepiride
Clinical Trial Phase	Trials
Phase 4	9
Phase 3	7
N/A	2

Clinical Trial Status

Clinical Trial Status for Pioglitazone Hydrochloride And Glimepiride
Clinical Trial Phase	Trials
Completed	14
Unknown status	4
Active, not recruiting	1

Clinical Trial Sponsors for Pioglitazone Hydrochloride And Glimepiride

Sponsor Name

Sponsor Name for Pioglitazone Hydrochloride And Glimepiride
Sponsor	Trials
Takeda	6
IKFE Institute for Clinical Research and Development	2
Phenomix	1

Sponsor Type

Sponsor Type for Pioglitazone Hydrochloride And Glimepiride
Sponsor	Trials
Other	15
Industry	13

Clinical Trials, Market Analysis, and Projections for Pioglitazone Hydrochloride and Glimepiride

Introduction

Pioglitazone hydrochloride and glimepiride are two oral antihyperglycemic agents commonly used in the management of type 2 diabetes mellitus. This article will delve into recent clinical trials, market analysis, and projections for these drugs, particularly when used in combination.

Clinical Efficacy of Pioglitazone and Glimepiride

Glycemic Control

Clinical trials have consistently shown that both pioglitazone and glimepiride are effective in controlling blood glucose levels in patients with type 2 diabetes. Pioglitazone, a thiazolidinedione, improves insulin sensitivity in muscle and adipose tissue and inhibits hepatic gluconeogenesis, leading to lower plasma glucose and insulin levels[2].

Glimepiride, a sulfonylurea, stimulates insulin release from the pancreatic beta cells, reducing both fasting and postprandial glucose levels. When combined, these drugs have an additive effect on glycemic control, as demonstrated in several studies[2][4].

Cardiovascular Risk Reduction

A significant aspect of the clinical efficacy of these drugs is their impact on cardiovascular risk factors. A randomized prospective study found that pioglitazone, when added to metformin, was more effective than glimepiride in reducing the AGE/s-RAGE ratio, a marker for renal and cardiovascular diseases, over a 5-year period[1].

Another study highlighted that pioglitazone reduced the progression of carotid intima-media thickness (CIMT), a surrogate marker for atherosclerosis and cardiovascular risk, more effectively than glimepiride[5].

Safety and Tolerability

Adverse Effects

Both pioglitazone and glimepiride have well-documented side effect profiles. Pioglitazone is associated with weight gain, edema, and a slight increase in the risk of heart failure. It also causes mild decreases in hemoglobin and hematocrit levels[3].

Glimepiride, on the other hand, is more likely to cause hypoglycemia, especially when used in combination with other antidiabetic agents. It does not significantly alter plasma lipoprotein profiles, which is a favorable aspect compared to some other antidiabetic drugs[2].

Long-Term Safety

Long-term safety data indicate that while both drugs are generally well-tolerated, there are concerns about the long-term use of thiazolidinediones like pioglitazone. Health Canada and the US FDA have issued safety reminders about the risk of heart failure associated with these drugs[3].

Market Analysis

Market Demand

The global demand for antidiabetic drugs is increasing due to the rising prevalence of type 2 diabetes. With approximately 90% of diabetes cases being type 2, the market for drugs like pioglitazone and glimepiride is substantial[3].

Combination Therapy

The combination of pioglitazone and glimepiride, marketed as DUETACT, offers a convenient and effective treatment option for patients with inadequately controlled type 2 diabetes. This combination leverages the complementary mechanisms of action of both drugs, enhancing glycemic control and reducing cardiovascular risk[2].

Budget Impact

A budget impact analysis suggests that the introduction of thiazolidinediones like pioglitazone into formularies could result in a significant increase in drug expenditures. However, the improved glycemic control and potential reduction in long-term complications could offset these costs[3].

Projections

Future Market Trends

Given the growing diabetes population and the need for effective combination therapies, the market for pioglitazone and glimepiride is expected to grow. The convenience of a single tablet containing both drugs (DUETACT) is likely to increase patient compliance and simplify treatment regimens[2].

Regulatory Considerations

Regulatory bodies continue to monitor the safety and efficacy of these drugs. Future projections will depend on ongoing and future clinical trials that assess the long-term safety and efficacy of these combination therapies[3].

Emerging Markets

In regions like India, where the prevalence of diabetes is projected to increase significantly, the demand for affordable and effective antidiabetic drugs is expected to rise. The triple combination of glimepiride, pioglitazone, and metformin has shown promising results in such populations, indicating a potential for growth in emerging markets[4].

Key Takeaways

• Clinical Efficacy: Pioglitazone and glimepiride are effective in controlling blood glucose levels and reducing cardiovascular risk factors.
• Safety and Tolerability: Both drugs have distinct side effect profiles, with pioglitazone associated with weight gain and edema, and glimepiride with a higher risk of hypoglycemia.
• Market Analysis: The combination therapy of pioglitazone and glimepiride is in high demand due to its efficacy and convenience.
• Projections: The market for these drugs is expected to grow, driven by the increasing prevalence of type 2 diabetes and the need for effective combination therapies.

FAQs

What is the primary mechanism of action of pioglitazone?

Pioglitazone primarily acts by decreasing insulin resistance, improving sensitivity to insulin in muscle and adipose tissue, and inhibiting hepatic gluconeogenesis[2].

How does glimepiride compare to pioglitazone in terms of cardiovascular risk reduction?

Pioglitazone has been shown to reduce cardiovascular risk factors more effectively than glimepiride, particularly in reducing the AGE/s-RAGE ratio and CIMT progression[1][5].

What are the common side effects of the combination therapy of pioglitazone and glimepiride?

Common side effects include weight gain, edema, and an increased risk of heart failure with pioglitazone, and hypoglycemia with glimepiride[2][3].

How does the combination of pioglitazone and glimepiride impact glycemic control?

The combination of pioglitazone and glimepiride has an additive effect on glycemic control, improving both fasting and postprandial glucose levels and reducing HbA1c levels[2][4].

What are the long-term safety concerns associated with pioglitazone?

Long-term safety concerns include an increased risk of heart failure and the need for ongoing monitoring of cardiovascular health[3].

Sources

1. Frontiers in Endocrinology: "Anti-diabetic combination therapy with pioglitazone or glimepiride added to metformin on the AGE-RAGE axis: a randomized prospective study"[1].
2. FDA Label: "DUETACTTM (pioglitazone hydrochloride and glimepiride) tablets"[2].
3. Canadian Coordinating Office for Health Technology Assessment: "Rosiglitazone and Pioglitazone for the Treatment of Type 2 Diabetes Mellitus"[3].
4. PubMed: "Evaluation of efficacy and safety of fixed dose combination of glimepiride 2 mg plus pioglitazone hydrochloride 15 mg plus metformin SR 500 mg in patients with type 2 diabetes mellitus"[4].
5. USC Journal: "Effect of Pioglitazone Compared with Glimepiride on Carotid Intima-Media Thickness in Type 2 Diabetes"[5].