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

NCT ID: NCT00727857

Last Updated: 2011-07-29

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

600 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-06-30

Study Completion Date

2008-08-31

Brief Summary

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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

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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.

Conditions

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Diabetes Mellitus

Keywords

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Glucose Metabolism Disorder Dysmetabolic Syndrome Type II Diabetes Diabetes Mellitus, Lipoatrophic Dyslipidemia Drug Therapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Pioglitazone 15 mg /Metformin 850 mg BID

Group Type EXPERIMENTAL

Pioglitazone and metformin

Intervention Type DRUG

Pioglitazone 15 mg /metformin 850 mg combination, tablets, orally, twice daily for up to 24 weeks.

Pioglitazone 15 mg BID

Group Type ACTIVE_COMPARATOR

Pioglitazone

Intervention Type DRUG

Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks.

Metformin 850 mg BID

Group Type ACTIVE_COMPARATOR

Metformin

Intervention Type DRUG

Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Interventions

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Pioglitazone and metformin

Pioglitazone 15 mg /metformin 850 mg combination, tablets, orally, twice daily for up to 24 weeks.

Intervention Type DRUG

Pioglitazone

Pioglitazone 15 mg, tablets, orally, twice daily for up to 24 weeks.

Intervention Type DRUG

Metformin

Metformin 850 mg, tablets, orally, twice daily for up to 24 weeks.

Intervention Type DRUG

Other Intervention Names

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ACTOPLUS MET ACTOS® AD4833 Fortamet Glucophage Glucophage XR Glumetza Riomet

Eligibility Criteria

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Inclusion Criteria

* Has type 2 diabetes.
* Has received no treatment with antidiabetic medication in the 12 weeks prior to Screening, other than short-term use defined as less than or equal to 15 days.
* A glycosylated hemoglobin greater than or equal to 7.5% and less than or equal to 10.0% at Screening.
* Body mass index less than or equal to 45 kg/m2.
* Has received counseling on lifestyle modification for type 2 diabetes, including diet and exercise.
* Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
* Stable condition as determined by a physician.

Exclusion Criteria

* Type 1 diabetes.
* Unstable angina or heart failure of any etiology with New York Heart Association functional class III or IV.
* History of myocardial infarction, cerebrovascular accident, percutaneous coronary intervention, coronary artery bypass graft, or transient ischemic attack in the 6 months prior to Screening.
* Male participant has a serum creatinine level greater than or equal to 1.5 mg per dL or female subject has a serum creatinine level greater than or equal to 1.4 mg per dL.
* Has a triglyceride level greater than 500 mg per dL.
* Male participant has a hemoglobin level less than 10.5 g per dL or female subject has a hemoglobin level less than 10.0 g per dL.
* Alanine aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.
* History of drug abuse (defined as any illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 2 alcoholic drinks per day) within 2 years prior to Screening.
* Has been discontinued from a thiazolidinedione or metformin therapy due to lack of efficacy or clinical or laboratory signs of intolerance.
* Previous history of cancer, other than basal cell or stage 1 squamous cell carcinoma, that has not been in remission for at least 5 years prior to the first dose of study medication.
* History of acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma.
* Any disease or condition at Screening or Randomization that would compromise safety, might affect life expectancy, or make it difficult to successfully manage and follow the subject according to the protocol.
* Currently participating in another investigational study or has participated in an investigational study within 30 days prior to randomization.
* Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

* Antidiabetic medications other than study medication
* Chronically used oral or parenteral glucocorticoids
* Niacin greater than 200 mg per day, including niacin-containing products such as Advicor
* Chronically used steroid-joint injections
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Takeda

INDUSTRY

Sponsor Role lead

Responsible Party

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Takeda Global Research & Development Center, Inc.

Principal Investigators

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VP Clinical Science Strategy

Role: STUDY_DIRECTOR

Takeda

Locations

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Birmingham, Alabama, United States

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Haleyville, Alabama, United States

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Montgomery, Alabama, United States

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Pell City, Alabama, United States

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Anaheim, California, United States

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Artesia, California, United States

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Dinuba, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Norwalk, California, United States

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Orange, California, United States

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Santa Ana, California, United States

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Santa Monica, California, United States

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Pueblo, Colorado, United States

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Altamonte Springs, Florida, United States

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Coral Gables, Florida, United States

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Hialeah, Florida, United States

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Miami, Florida, United States

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Panama City, Florida, United States

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Plantation, Florida, United States

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Saint Cloud, Florida, United States

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St. Petersburg, Florida, United States

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Tampa, Florida, United States

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Columbus, Georgia, United States

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Boise, Idaho, United States

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Coeur d'Alene, Idaho, United States

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Chicago, Illinois, United States

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Flossmoor, Illinois, United States

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Peoria, Illinois, United States

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Elkhart, Indiana, United States

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Shawnee, Kansas, United States

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Southfield, Michigan, United States

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Chesterfield, Missouri, United States

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Billings, Montana, United States

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Elizabeth, New Jersey, United States

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Fayetteville, New York, United States

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New York, New York, United States

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Durham, North Carolina, United States

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Pinehurst, North Carolina, United States

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Cincinnati, Ohio, United States

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Perrysburg, Ohio, United States

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Zanesville, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Eugene, Oregon, United States

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Fleetwood, Pennsylvania, United States

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Norristown, Pennsylvania, United States

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Cranston, Rhode Island, United States

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Simpsonville, South Carolina, United States

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Varnville, South Carolina, United States

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Fayetteville, Tennessee, United States

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Corpus Christi, Texas, United States

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Dallas, Texas, United States

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El Paso, Texas, United States

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Houston, Texas, United States

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McAllen, Texas, United States

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Mission, Texas, United States

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New Braunfels, Texas, United States

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North Richland Hills, Texas, United States

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San Antonio, Texas, United States

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Bountiful, Utah, United States

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Salt Lake City, Utah, United States

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Petersburg, Virginia, United States

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Port Orchard, Washington, United States

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Spokane, Washington, United States

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Providencia-Santiago, , Chile

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Temuco, , Chile

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Zapopan, Jalisco, Mexico

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Monterrey, Nuevo León, Mexico

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Aibonito, , Puerto Rico

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Caguas, , Puerto Rico

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Ciales, , Puerto Rico

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Coto Laurel, , Puerto Rico

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Guayma, , Puerto Rico

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Guaynabo, , Puerto Rico

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Rio Piedras, , Puerto Rico

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Countries

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United States Chile Mexico Puerto Rico

References

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Perez A, Zhao Z, Jacks R, Spanheimer R. Efficacy and safety of pioglitazone/metformin fixed-dose combination therapy compared with pioglitazone and metformin monotherapy in treating patients with T2DM. Curr Med Res Opin. 2009 Dec;25(12):2915-23. doi: 10.1185/03007990903350011.

Reference Type BACKGROUND
PMID: 19827910 (View on PubMed)

Perez A, Jacks R, Arora V, Spanheimer R. Effects of pioglitazone and metformin fixed-dose combination therapy on cardiovascular risk markers of inflammation and lipid profile compared with pioglitazone and metformin monotherapy in patients with type 2 diabetes. J Clin Hypertens (Greenwich). 2010 Dec;12(12):973-82. doi: 10.1111/j.1751-7176.2010.00389.x. Epub 2010 Nov 8.

Reference Type RESULT
PMID: 21122063 (View on PubMed)

Related Links

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Other Identifiers

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U1111-1114-0371

Identifier Type: REGISTRY

Identifier Source: secondary_id

01-06-TL-OPIMET-008

Identifier Type: -

Identifier Source: org_study_id