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Efficacy and Safety of Pioglitazone and Metformin Combination Therapy in Treating Type 2 Diabetes Mellitus.

Phase 3
Completed
Conditions
Diabetes Mellitus
Interventions
Registration Number
NCT00727857
Lead Sponsor
Takeda
Brief Summary

The purpose of this study is to determine the efficacy of pioglitazone, twice daily (BID), combined with metformin versus pioglitazone taken alone and metformin taken alone in treating Type 2 Diabetes Mellitus.

Detailed Description

Pioglitazone hydrochloride (ACTOS®) is a member of a class of oral antidiabetic agents known as thiazolidinediones, which act by reducing insulin resistance. Insulin resistance is a key feature of dysmetabolic syndrome and has been suggested to be the common pathophysiologic basis of both atherosclerosis and type 2 diabetes. Pioglitazone binds to peroxisome proliferator-activated receptors, an effect that is associated with altered transcription of genes capable of influencing carbohydrate and lipid metabolism.

Metformin hydrochloride is an oral antihyperglycemic drug not chemically or pharmacologically related to thiazolidinediones. Metformin is a biguanide, which has been shown to be effective in improving glycemic control in diabetic patients. Metformin inhibits hepatic glucose production, most likely through an inhibition of gluconeogenesis, and its use is associated with an improvement in tissue sensitivity to insulin. In accordance with published algorithms for the use of combination therapy for the treatment of type 2 diabetes, physicians have traditionally combined metformin with other antidiabetic agents.

This study will determine the effect of a fixed-dose combination of metformin with pioglitazone, compared to metformin monotherapy and pioglitazone monotherapy.

Study participation is anticipated to be approximately 6.5 months.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
600
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Pioglitazone 15 mg /Metformin 850 mg BIDPioglitazone and metformin-
Pioglitazone 15 mg BIDPioglitazone-
Metformin 850 mg BIDMetformin-
Primary Outcome Measures
NameTimeMethod
Percent Change From Baseline in Glycosylated HemoglobinBaseline and Week 24

The change between the value of Glycosylated Hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at final visit or week 24 and Glycosylated Hemoglobin collected at baseline.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Fasting Plasma GlucoseBaseline and Week 24

The change between the value of Fasting Plasma Glucose collected at final visit or week 24 and Fasting Plasma Glucose collected at baseline.

Change From Baseline in Fasting InsulinBaseline and Week 24

The change between the Fasting Insulin value collected at final visit or week 24 and Fasting Insulin collected at baseline.

Change From Baseline in Homeostasis Model Assessment - Insulin ResistanceBaseline and Week 24

The change between Homeostasis Model Assessment of Insulin Resistance collected at final visit or week 24 and Homeostasis Model Assessment of Insulin Resistance collected at baseline. Homeostasis Model Assessment measures insulin resistance, calculated by insulin times glucose, divided by a constant (22.5).

Median Percent Change From Baseline in High Sensitivity C-reactive ProteinBaseline and Week 24

Measurement for High Sensitivity C-reactive Protein was collected at final visit or week 24 and at baseline. Percent change from baseline is calculated as: \[(Week 24 - baseline levels)/baseline\]\*100

Change From Baseline in AdiponectinBaseline and Week 24

The change between Adiponectin collected at final visit or week 24 and Adiponectin collected at baseline.

Change From Baseline in Total CholesterolBaseline and Week 24

The change between Total Cholesterol collected at final visit or week 24 and Total Cholesterol collected at baseline.

Change From Baseline in Low-Density Lipoprotein CholesterolBaseline and Week 24

The change between Low-Density Lipoprotein Cholesterol collected at final visit or week 24 and Low-Density Lipoprotein Cholesterol collected at baseline.

Change From Baseline in High-Density Lipoprotein CholesterolBaseline and Week 24

The change between High-Density Lipoprotein Cholesterol collected at final visit or week 24 and High-Density Lipoprotein Cholesterol collected at baseline.

Change From Baseline in TriglyceridesBaseline and Week 24

The change between Triglycerides collected at final visit or week 24 and Triglycerides collected at baseline.

Change From Baseline in Mean Low Density Lipoprotein Particle ConcentrationBaseline and Week 24

The change between Low Density Lipoprotein particle concentration collected at final visit or week 24 and Low Density Lipoprotein particle concentration collected at baseline.

Change From Baseline in Mean Low Density Lipoprotein Particle SizeBaseline and Week 24

The change between Low Density Lipoprotein collected at final visit or week 24 and Low Density Lipoprotein collected at baseline.

Change From Baseline in Large Low Density Lipoprotein (L3) ConcentrationBaseline and Week 24

The change between Large Low Density Lipoprotein collected at final visit or week 24 and Large Low Density Lipoprotein collected at baseline.

Change From Baseline in Intermediate-Density Low Density Lipoprotein ConcentrationBaseline and Week 24

The change between Intermediate-Density Low Density Lipoprotein collected at final visit or week 24 and Intermediate-Density Low Density Lipoprotein collected at baseline

Change From Baseline in Medium-Small Low Density Lipoprotein ConcentrationBaseline and Week 24

The change between Medium-Small Low Density Lipoprotein collected at final visit or week 24 and Medium-Small Low Density Lipoprotein collected at baseline

Change From Baseline in Small Low Density Lipoprotein ConcentrationBaseline and Week 24

The change between Small Low Density Lipoprotein collected at final visit or week 24 and Small Low Density Lipoprotein collected at baseline

Change From Baseline in Very Small Low Density Lipoprotein ConcentrationBaseline and Week 24

The change between Very Small Low Density Lipoprotein collected at final visit or week 24 and Very Small Low Density Lipoprotein collected at baseline

Change From Baseline in Mean High Density Lipoprotein Particle ConcentrationBaseline and Week 24

The change between High Density Lipoprotein collected at final visit or week 24 and High Density Lipoprotein collected at baseline.

Change From Baseline in Mean High Density Lipoprotein Particle SizeBaseline and Week 24

The change between High Density Lipoprotein collected at final visit or week 24 and High Density Lipoprotein collected at baseline.

Change From Baseline in Large High Density Lipoprotein (H4+H5) ConcentrationBaseline and Week 24

The change between Large High Density Lipoprotein collected at final visit or week 24 and Large High Density Lipoprotein collected at baseline

Change From Baseline in Intermediate-Medium High Density Lipoprotein (H3) ConcentrationBaseline and Week 24

The change between Intermediate-Medium High Density Lipoprotein collected at final visit or week 24 and Intermediate-Medium High Density Lipoprotein collected at baseline

Change From Baseline in Small High Density Lipoprotein (H1+H2) ConcentrationBaseline and Week 24

The change between Small High Density Lipoprotein collected at final visit or week 24 and Small High Density Lipoprotein collected at baseline

Change From Baseline in Mean Very Low Density Lipoprotein Particle ConcentrationBaseline and Week 24

The change between Very Low Density Lipoprotein collected at final visit or week 24 and Very Low Density Lipoprotein collected at baseline.

Change From Baseline in Mean Very Low Density Lipoprotein Particle SizeBaseline and Week 24

The change between Very Low Density Lipoprotein collected at final visit or week 24 and Very Low Density Lipoprotein collected at baseline.

Change From Baseline in Large-Chylomicrons Very Low Density Lipoprotein ConcentrationBaseline and Week 24

The change between Large-Chylomicrons Very Low Density Lipoprotein collected at final visit or week 24 and Large-Chylomicrons Very Low Density Lipoprotein collected at baseline

Change From Baseline in Medium-Intermediate Very Low Density Lipoprotein (V3+V4) ConcentrationBaseline and Week 24

The change between Medium-Intermediate Very Low Density Lipoprotein collected at final visit or week 24 and Medium-Intermediate Very Low Density Lipoprotein collected at baseline

Change From Baseline in Small Very Low Density Lipoprotein (V1+V2) ConcentrationBaseline and Week 24

The change between Small Very Low Density Lipoprotein collected at final visit or week 24 and Small Very Low Density Lipoprotein collected at baseline

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