CLINICAL TRIALS PROFILE FOR METFORMIN HYDROCHLORIDE; PIOGLITAZONE HYDROCHLORIDE

All Clinical Trials for Metformin Hydrochloride; Pioglitazone Hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
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.
NCT00097279 ↗	Comparison of Biphasic Insulin Aspart 70/30 With Anti-Diabetic Drugs in Subjects With Type 2 Diabetes	Completed	Novo Nordisk A/S	Phase 3	2004-08-01	This trial is conducted in the United States of America (USA). The purpose of this study is to test whether biphasic insulin aspart 70/30 is a safe and at least as effective alternative in combination with two oral anti-diabetics compared to the two oral anti-diabetics alone for the control of blood glucose.
NCT00108615 ↗	Effects of Insulin Sensitizers in Subjects With Impaired Glucose Tolerance	Completed	US Department of Veterans Affairs	Phase 4	2004-01-01	Subjects with impaired glucose tolerance will be randomized to receive pioglitazone or metformin for 10 weeks. Measurements of insulin sensitivity, body composition, glucose tolerance, and muscle lipid accumulation will be performed. Adipose tissue and muscle biopsies are performed. The goal of the study is to determine whether the lipotoxiciy of impaired glucose tolerance is ameliorated by pioglitazone.
NCT00108615 ↗	Effects of Insulin Sensitizers in Subjects With Impaired Glucose Tolerance	Completed	VA Office of Research and Development	Phase 4	2004-01-01	Subjects with impaired glucose tolerance will be randomized to receive pioglitazone or metformin for 10 weeks. Measurements of insulin sensitivity, body composition, glucose tolerance, and muscle lipid accumulation will be performed. Adipose tissue and muscle biopsies are performed. The goal of the study is to determine whether the lipotoxiciy of impaired glucose tolerance is ameliorated by pioglitazone.
NCT00159211 ↗	Abdominal Adipose Tissue Distribution in Type 2 Diabetic Patients Treated During 6 Months With Pioglitazone or Insulin	Terminated	Laboratoires Takeda	N/A	2005-05-01	In type 2 diabetic patients with poor glycemic control despite maximum "classic" oral treatment, bed time insulin therapy may lead to a parallel increase in abdominal visceral and subcutaneous fat, whereas pioglitazone treatment should lead to a stability (or even a decrease ) in visceral and an increase in subcutaneous abdominal fat. As visceral fat mass is correlated with insulin-resistance and cardio-vascular risk, the evolution of visceral abdominal fat in type 2 diabetic patients is of great importance. Main objective: To compare visceral and subcutaneous abdominal fat compartment after a six-month bed time insulin or pioglitazone treatment in type 2 diabetic patients with poor glycemic control despite a maximal oral treatment with metformin and sulfonylureas. The study hypothesis is that quantity of visceral and subcutaneous abdominal adipose tissue should differently evolute comparing a 6 month treatment with pioglitazone® (30 or 45mg/j) or NPH " bed-time " insulin (0.2u/kg/

Clinical Trial Conditions for Metformin Hydrochloride; Pioglitazone Hydrochloride

Condition Name

Condition Name for Metformin Hydrochloride; Pioglitazone Hydrochloride
Intervention	Trials
Diabetes Mellitus, Type 2	31
Type 2 Diabetes Mellitus	30
Type 2 Diabetes	24
Diabetes Mellitus	17

Condition MeSH

Condition MeSH for Metformin Hydrochloride; Pioglitazone Hydrochloride
Intervention	Trials
Diabetes Mellitus	104
Diabetes Mellitus, Type 2	99
Fatty Liver	15
Non-alcoholic Fatty Liver Disease	13

Clinical Trial Locations for Metformin Hydrochloride; Pioglitazone Hydrochloride

Trials by Country

Trials by Country for Metformin Hydrochloride; Pioglitazone Hydrochloride
Location	Trials
United States	786
Germany	44
Canada	40
India	40
Mexico	30

Trials by US State

Trials by US State for Metformin Hydrochloride; Pioglitazone Hydrochloride
Location	Trials
Texas	36
Florida	30
California	30
North Carolina	27
Georgia	25

Clinical Trial Progress for Metformin Hydrochloride; Pioglitazone Hydrochloride

Clinical Trial Phase

Clinical Trial Phase for Metformin Hydrochloride; Pioglitazone Hydrochloride
Clinical Trial Phase	Trials
Phase 4	67
Phase 3	43
Phase 2/Phase 3	3

Clinical Trial Status

Clinical Trial Status for Metformin Hydrochloride; Pioglitazone Hydrochloride
Clinical Trial Phase	Trials
Completed	105
Unknown status	17
Recruiting	11

Clinical Trial Sponsors for Metformin Hydrochloride; Pioglitazone Hydrochloride

Sponsor Name

Sponsor Name for Metformin Hydrochloride; Pioglitazone Hydrochloride
Sponsor	Trials
Takeda	21
Novo Nordisk A/S	8
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	7

Sponsor Type

Sponsor Type for Metformin Hydrochloride; Pioglitazone Hydrochloride
Sponsor	Trials
Other	137
Industry	86
NIH	8

Metformin Hydrochloride and Pioglitazone Hydrochloride: Clinical Trials, Market Analysis, and Projections

Introduction

The combination of metformin hydrochloride and pioglitazone hydrochloride is a widely used treatment for type 2 diabetes, offering a dual mechanism of action that enhances glycemic control and improves insulin sensitivity. This article delves into the clinical trials, market analysis, and future projections for this combination drug.

Clinical Trials Overview

PROactive Study

One of the significant clinical trials involving pioglitazone is the PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events) study. This randomized, double-blind outcome study assesses the effect of pioglitazone on the secondary prevention of macrovascular events in patients with type 2 diabetes who have a history of macrovascular disease. Patients were randomized to receive pioglitazone or placebo in addition to their existing therapy, with the primary endpoint being the time from randomization to the occurrence of a new macrovascular event or death. The study aims to evaluate whether pioglitazone lowers the incidence of macrovascular complications in high-risk patients[1].

Pioglitazone and Metformin Combination Study

A 16-week, double-blind study investigated the efficacy and tolerability of pioglitazone in combination with metformin in patients with type 2 diabetes. Patients receiving pioglitazone 30 mg plus metformin showed significant improvements in HbA1c and fasting plasma glucose (FPG) levels compared to those receiving placebo plus metformin. The study also noted positive effects on serum lipid levels and no evidence of drug-induced hepatotoxicity. The open-label extension of this study maintained these benefits over 72 weeks[3].

Triple Drug Combination Study

Another study evaluated the efficacy and safety of a triple drug combination of glimepiride, pioglitazone, and metformin in Indian patients with type 2 diabetes. This open, phase III, multicentric study found that the combination significantly reduced triglyceride, low-density lipoprotein, and total cholesterol levels, achieving the recommended goals for fasting blood glucose and HbA1c levels set by the American Diabetic Association[4].

Mechanism of Action

Metformin

Metformin works by reducing hepatic glucose production, enhancing insulin sensitivity, and decreasing the absorption of sugar from the stomach. It is generally well-tolerated and is a first-line treatment for type 2 diabetes[5].

Pioglitazone

Pioglitazone, a peroxisome proliferator-activated receptor agonist, increases peripheral glucose utilization and reduces insulin resistance. It also has anti-inflammatory and vascular properties, which are beneficial in managing the cardiovascular risks associated with diabetes[1][5].

Market Analysis

Market Size and Forecast

The global Metformin-Pioglitazone market was valued at USD 811.75 million in 2020 and is projected to reach USD 1,127.78 million by 2028, growing at a CAGR of 4.37% from 2021 to 2028. This growth is driven by the rising prevalence of type 2 diabetes and the increasing adoption of oral antidiabetic drugs[2].

Market Segmentation

The market is segmented by type, with tablets containing 15 mg pioglitazone/1000 mg metformin HCl and 30 mg pioglitazone/1000 mg metformin HCl being the primary forms. The 15 mg pioglitazone/1000 mg metformin HCl segment accounted for the largest market share in 2020 and is projected to grow at the highest CAGR during the forecast period[2].

Regional Analysis

North America and Europe are experiencing steady growth, driven by government initiatives and increasing consumer awareness. However, the Asia-Pacific region, particularly China, leads the global market due to robust domestic demand, supportive policies, and a strong manufacturing base[5].

Market Drivers and Restraints

Drivers

• Rising Prevalence of Type 2 Diabetes: The increasing number of people with type 2 diabetes globally is a significant driver for the market.
• Increasing Rates of Obesity: Obesity is a major risk factor for type 2 diabetes, contributing to the growing demand for Metformin-Pioglitazone.
• Growing Adoption of Oral Antidiabetic Drugs: The rising approvals and adoption of oral antidiabetic drugs are boosting the market[2].

Restraints

• Side Effects and FDA Black Box Warning: The medication comes with a black box warning due to serious adverse events such as injuries and deaths, which can discourage some patients from using it[2].

Competitive Landscape

The market is competitive, with several key players including Takeda Pharmaceuticals, Mylan, Teva, Sandoz, Aurobindo Pharma, MACLEODS, Torrent Pharmaceuticals, Wellona Pharma, BLUE CROSS, and Neurocon Inc. These companies are focusing on expanding their market share through various strategies such as product differentiation and regional expansion[5].

Impact of COVID-19

The COVID-19 pandemic has had a mixed impact on the Metformin-Pioglitazone market. While there has been an increased focus on healthcare and managing chronic conditions like diabetes, supply chain disruptions and economic constraints have also affected market growth. However, the long-term demand for diabetes medications remains strong due to the ongoing rise in diabetes prevalence[2].

Future Projections

Market Growth

The market is expected to continue growing due to the increasing prevalence of type 2 diabetes and the aging population. By 2030, the number of people with type 2 diabetes is projected to reach 36 million, and by 2045, it is expected to be 81 million, further driving the demand for Metformin-Pioglitazone[2].

Technological Advancements

Advancements in drug formulation and delivery systems, as well as the development of new combination therapies, are expected to enhance the market. Additionally, government initiatives and public health campaigns aimed at managing diabetes will support market growth[5].

Regional Expansion

The Asia-Pacific region is anticipated to continue leading the market due to its large population, increasing healthcare expenditure, and supportive government policies. Other regions, such as North America and Europe, will also see steady growth driven by consumer awareness and government initiatives[5].

Key Takeaways

• The combination of metformin and pioglitazone is effective in managing type 2 diabetes by improving glycemic control and insulin sensitivity.
• Clinical trials have shown significant benefits of this combination in reducing HbA1c and FPG levels, as well as improving lipid profiles.
• The global Metformin-Pioglitazone market is projected to grow at a CAGR of 4.37% from 2021 to 2028.
• The market is driven by the rising prevalence of type 2 diabetes and the increasing adoption of oral antidiabetic drugs.
• Key players are focusing on product differentiation and regional expansion to capture market share.

FAQs

Q: What is the primary mechanism of action of metformin and pioglitazone in treating type 2 diabetes?

A: Metformin reduces hepatic glucose production, enhances insulin sensitivity, and decreases sugar absorption from the stomach. Pioglitazone increases peripheral glucose utilization and reduces insulin resistance[5].

Q: What are the key findings of the PROactive study involving pioglitazone?

A: The PROactive study assesses the effect of pioglitazone on the secondary prevention of macrovascular events in patients with type 2 diabetes. It aims to evaluate whether pioglitazone lowers the incidence of macrovascular complications in high-risk patients[1].

Q: How does the combination of metformin and pioglitazone impact serum lipid levels?

A: Studies have shown that the combination of metformin and pioglitazone significantly improves serum lipid levels by reducing triglycerides and increasing high-density lipoprotein cholesterol[3].

Q: What are the major drivers of the Metformin-Pioglitazone market?

A: The rising prevalence of type 2 diabetes, increasing rates of obesity, and growing adoption of oral antidiabetic drugs are the major drivers of the market[2].

Q: Which region is expected to lead the global Metformin-Pioglitazone market in the future?

A: The Asia-Pacific region, particularly China, is expected to lead the global market due to robust domestic demand, supportive policies, and a strong manufacturing base[5].

Sources

1. The Prospective Pioglitazone Clinical Trial in Macrovascular Events - Diabetes Care, 2004.
2. Metformin-Pioglitazone Market Size, Share, Trends, Scope & Forecast - Verified Market Research.
3. Pioglitazone hydrochloride in combination with metformin - PubMed.
4. Evaluation of efficacy and safety of fixed dose combination of glimepiride, pioglitazone, and metformin - PubMed.
5. Global Metformin Pioglitazone Market - Industry Research Biz.