Efficacy and Safety Study of Pioglitazone Combined With Metformin on Metabolic Syndrome in Subjects With Type 2 Diabetes (PRISMA)
|Diabetes Mellitus||Drug: Pioglitazone and Metformin Drug: Metformin||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Double-blind, Randomized, Multicenter, Parallel-Group Study to Evaluate the Effects of Pioglitazone on Metabolic Syndrome in Patients With Type 2 Diabetes Treated With Metformin|
- Increase in High-Density Lipoprotein cholesterol levels. [ Time Frame: Final Visit. ]
- The change from Baseline in Metabolic Syndrome, as defined by the International Diabetes Federation (aggregate waist circumference, fasting plasma glucose, triglycerides and high-density lipoprotein cholesterol). [ Time Frame: Weeks: 8 and 24. ]
- The change from Baseline in Metabolic Syndrome, as defined by the International Diabetes Federation (blood pressure). [ Time Frame: At all Visits. ]
- The change from Baseline in Individual Metabolic Parameters (insulin sensitivity and beta-cell function, inflammatory cytokines, adipokines, endothelial functionality). [ Time Frame: Weeks: 8 and 24. ]
- Adverse Events. [ Time Frame: At all Visits. ]
- The change from Baseline in Laboratory Parameters (hematology, chemistry and urinalysis). [ Time Frame: Weeks: 8 and 24. ]
|Study Start Date:||January 2007|
|Study Completion Date:||February 2008|
|Primary Completion Date:||February 2008 (Final data collection date for primary outcome measure)|
|Experimental: Pioglitazone + Metformin||
Drug: Pioglitazone and Metformin
Pioglitazone 15 mg, tablets, orally, two-times daily and metformin stable dose, orally, three-times daily for 4 weeks; then increased to pioglitazone 15 mg, tablets, orally, three-times daily and metformin stable dose, orally, three-times daily for up to 20 weeks.
|Active Comparator: Metformin||
Pioglitazone placebo-matching tablets, orally, two-times daily and metformin stable dose, orally, three-times daily for 4 weeks; then increased to pioglitazone placebo-matching tablets, orally, three-times daily and metformin stable dose, orally, three-times daily for up to 20 weeks.
Diabetes is none of the most common, chronic diseases worldwide and affects nearly 200 million people. It is the fourth or fifth leading cause of death in developed countries, and it is expected that diabetes will reach epidemic proportions, affecting 333 million people globally by 2025.
The metabolic syndrome is a cluster of the most dangerous cardiovascular risk factors and includes diabetes and pre-diabetes in addition to abdominal obesity, low high-density lipoprotein cholesterol, high triglycerides and hypertension. It is estimated that around a quarter of the world's adult population has metabolic syndrome, and are twice as likely to die and three times as likely to have a heart attack or stroke when compared to people without the syndrome. In addition, non-diabetic people with metabolic syndrome have a fivefold greater risk of developing type 2 diabetes. The clustering of cardiovascular risk factors that typifies the metabolic syndrome is now considered the driving force for a cardiovascular disease epidemic.
Metabolic syndrome has been recently defined by a Consensus Conference of the International Diabetes Federation as a cluster of clinical and laboratory signs characterized by the presence of abnormal deposition of fat tissue in the abdomen and visceral districts, and at least two other clinical and laboratory abnormalities, including altered glucose metabolism or type 2 diabetes and decreased levels of high-density lipoprotein cholesterol. One of the underlying pathophysiological mechanisms of metabolic syndrome is insulin resistance, characterized by an increased glucose output from the liver, and reduced glucose uptake in the muscle and adipose tissue cells. Drugs whose mechanism of action consists of increasing insulin sensitivity in the target tissues are able to reduce the clinical manifestations and consequences of metabolic syndrome.
While each individual component of metabolic syndrome confers an increased risk of cardiovascular-related complications or death, this risk is more pronounced when the syndrome itself is present. The more components of metabolic syndrome are evident, the higher is the cardiovascular mortality rate.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00772174
|Study Director:||Medical Director||Takeda|