Clinical trial NCT00770653: Efficacy of Pioglitazone/Metformin Combination Therapy in Subjects With Type 2 Diabetes Mellitus and Dyslipidemia.
Official title: Effects of a Pioglitazone/Metformin Fixed Combination in Comparison to Metformin in Combination With Glimepiride on Diabetic Dyslipidemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus
Dyslipidemias
Keywords: Glucose Metabolism Disorder
Dysmetabolic Syndrome
Type II Diabetes
Diabetes Mellitus, Lipoatrophic
Dyslipidemia
Hyperlipidemias
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-10-10
Enrollment: 305
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare pioglitazone and metformin combination therapy, twice daily (BID), to glimepiride and metformin combination therapy for treating diabetic subjects with dyslipidemia.

Detailed description: Insulin resistance is a major endocrinopathy preceding the development of hyperglycemia, diabetic dyslipidemia and cardiovascular disease in type 2 diabetes. The most common pattern of dyslipidemia in patients with type 2 diabetes are elevated triglyceride levels, decreased hih-density lipoprotein cholesterol and a predominance of small dense low-density lipoprotein particles. Each of these dyslipidemia features is associated with an increased risk of cardiovascular events.

Pioglitazone and Metformin are established drugs which can be used for the treatment of type 2 diabetes. This study will investigate the effects of treatment with fixed Pioglitazone/Metformin combination therapy of Metformin and Glimepiride in Metformin-pretreated type 2 diabetic patients with dyslipidemia.

Total participation time in this study is anticipated to be approximately 24 weeks.

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes according to the American Diabetes Association Criteria.
* Treatment with individual maximal tolerated dose of metformin (850 - 2000 mg) as monotherapy within the last 12 weeks.
* Glycosylated Hemoglobin greater than or equal to 6.5% and less than or equal to 9%.
* Dyslipidemia defined as high-density lipoprotein cholesterol less than or equal to 1.03 mmol/l (40 mg/dL) and/or triglycerides greater than or equal to 1.7 mmol/l (150 mg/dL).
* 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.

Exclusion Criteria:

* Type 1 diabetes mellitus.
* Insulin-dependent type 2 diabetes mellitus.
* Treatment or history of treatment with any insulin formulation other than emergency for more than 2 weeks.
* Treatment with other oral antidiabetic drugs in addition to metformin within the last 12 weeks.
* Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures.
* Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

  * Heparin (and heparin-like drugs)
  * coumarin
  * phenprocoumon
  * hirudin
  * Protein C
  * Fondaparinux
  * antithrombin III
  * Peroxisome Proliferation Activating Receptor (gamma) agonists
  * Treatment within the last 12 weeks with:

    * fibrates
    * gemfibrozil
    * niacin
    * months
    * Rifampicin
  * Changes in dosage of any statin treatment to lower low-density lipoprotein within 2 weeks before study entry and during study participation interval.
  * Changes in dosage of any anticoagulant treatment with acetyl salicylic acid and/or clopidogrel within 2 weeks before study entry and during study participation interval.
  * Start of statin and/or anticoagulant treatment during study participation interval.
* History of severe or multiple allergies and/ or acute severe infections.
* Have had more than one unexplained episode of severe hypoglycemia (defined as requiring assistance of another person due to disabling hypoglycemia) within 6 months prior to screening visit.
* Progressive fatal disease.
* Any elective surgery during study participation.
* History of drug or alcohol abuse within the last 5 years.
* A history of significant cardiovascular (New York Heart Association stage I - IV), respiratory, gastrointestinal, hepatic (alanine aminotransferase and/or aspartate aminotransferase greater than 2.5 times the upper limit of the normal reference range), renal (serum creatinine greater than 1.2 mg/dL in women and greater than 1.5 mg/dL in men, glomerular filtration rate less than 60 ml/min as estimated by the Cockroft-Gault formula), neurological, psychiatric and/or hematological disease as judged by the investigator, history of macular edema.
* Blood donation within the last 30 days.

Primary outcomes:
measure: The Mean Increase From Baseline in High-Density Lipoprotein Cholesterol.
timeFrame: Baseline and Week 24.
Secondary outcomes:
measure: Change From Baseline in High-Density Lipoprotein Cholesterol.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in High-Density Lipoprotein/Low-Density Lipoprotein Ratio.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Triglycerides.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Low-Density Lipoprotein Subfractions.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Low-Density Lipoprotein Cholesterol.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Glycosylated Hemoglobin.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Fasting Intact Proinsulin.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Fasting Glucose.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Adiponectin.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in High Sensitivity C-reactive Protein (Original).
timeFrame: Baseline and Week 24.
measure: Change From Baseline in High Sensitivity C-reactive Protein (≤ 10 mg/L).
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Systolic Blood Pressure.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Diastolic Blood Pressure.
timeFrame: Baseline and Week 24.
measure: Intake of Study Medication Greater Than 80% and Less Than 120%.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Nitrotyrosine.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Soluble CD40 Ligand.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Matrix Metallo Proteinase-9.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Soluble Intracellular Adhesion Molecule.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Soluble Vascular Cell Adhesion Molecule.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Thromboxane B2.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Platelet Function.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in E-Selectin.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Von-Willebrand Factor.
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Erythrocyte Deformability (0.30%).
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Erythrocyte Deformability (0.60%)
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Erythrocyte Deformability (1.20).
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Erythrocyte Deformability (3.00).
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Erythrocyte Deformability (6.00).
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Erythrocyte Deformability (12.00).
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Erythrocyte Deformability (30.00).
timeFrame: Baseline and Week 24.
measure: Change From Baseline in Erythrocyte Deformability (60.00).
timeFrame: Baseline and Week 24.
Other outcomes:
Locations:
city: Bretten
country: Germany
state: Baden-Württemberg
city: Deggingen
country: Germany
state: Baden-Württemberg
city: Dettenheim
country: Germany
state: Baden-Württemberg
city: Künzelsau
country: Germany
state: Baden-Württemberg
city: Rottweil
country: Germany
state: Baden-Württemberg
city: Spaichingen
country: Germany
state: Baden-Württemberg
city: Stockach
country: Germany
state: Baden-Württemberg
city: Wangen
country: Germany
state: Baden-Württemberg
city: Augsburg
country: Germany
state: Bayern
city: Feldafing
country: Germany
state: Bayern
city: Furth im Wald
country: Germany
state: Bayern
city: Immenstadt
country: Germany
state: Bayern
city: Lichtenfels
country: Germany
state: Bayern
city: München
country: Germany
state: Bayern
city: Schweinfurt
country: Germany
state: Bayern
city: Waldkraiburg
country: Germany
state: Bayern
city: Wallerfing
country: Germany
state: Bayern
city: Weilersbach
country: Germany
state: Bayern
city: Würzburg
country: Germany
state: Bayern
city: Ketzin
country: Germany
state: Brandenburg
city: Rüdersdorf
country: Germany
state: Brandenburg
city: Bermerhaven
country: Germany
state: Bremen
city: Bensheim
country: Germany
state: Hessen
city: Ehrenberg
country: Germany
state: Hessen
city: Gersfeld
country: Germany
state: Hessen
city: Kassel
country: Germany
state: Hessen
city: Kelkheim
country: Germany
state: Hessen
city: Offenbach
country: Germany
state: Hessen
city: Schwerin
country: Germany
state: Mecklenburg-Vorpommern
city: Celle
country: Germany
state: Niedersachsen
city: Einbeck
country: Germany
state: Niedersachsen
city: Hannover
country: Germany
state: Niedersachsen
city: Hildesheim
country: Germany
state: Niedersachsen
city: Bad Berleburg
country: Germany
state: Nordrhein-Westfalen
city: Bad Laasphe
country: Germany
state: Nordrhein-Westfalen
city: Bad Oeynhausen
country: Germany
state: Nordrhein-Westfalen
city: Bocholt
country: Germany
state: Nordrhein-Westfalen
city: Dinslaken
country: Germany
state: Nordrhein-Westfalen
city: Dorsten
country: Germany
state: Nordrhein-Westfalen
city: Duisburg
country: Germany
state: Nordrhein-Westfalen
city: Essen
country: Germany
state: Nordrhein-Westfalen
city: Frechen
country: Germany
state: Nordrhein-Westfalen
city: Isselburg
country: Germany
state: Nordrhein-Westfalen
city: Kamen
country: Germany
state: Nordrhein-Westfalen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Marl
country: Germany
state: Nordrhein-Westfalen
city: Menden
country: Germany
state: Nordrhein-Westfalen
city: Münster
country: Germany
state: Nordrhein-Westfalen
city: Siegen
country: Germany
state: Nordrhein-Westfalen
city: Diez
country: Germany
state: Rheinland-Pfalz
city: Mainz
country: Germany
state: Rheinland-Pfalz
city: Neuwied
country: Germany
state: Rheinland-Pfalz
city: Rodenbach
country: Germany
state: Rheinland-Pfalz
city: Simmern
country: Germany
state: Rheinland-Pfalz
city: Magdeburg
country: Germany
state: Sachsen-Anhalt
city: Borna
country: Germany
state: Sachsen
city: Dresden
country: Germany
state: Sachsen
city: Meißen
country: Germany
state: Sachsen
city: Mittweida
country: Germany
state: Sachsen
city: Reinfeld
country: Germany
state: Schleswig-Holstein
city: Altenburg
country: Germany
state: Thüringen
city: Blankenhain
country: Germany
state: Thüringen
city: Berlin
country: Germany
city: Hamburg
country: Germany
Study officials:
affiliation: Takeda Pharma Gmbh, Aachen (Germany)
name: Medical Adviser Clinical Research
role: STUDY_DIRECTOR
References:
citation: Pfutzner A, Schondorf T, Tschope D, Lobmann R, Merke J, Muller J, Lehmann U, Fuchs W, Forst T. PIOfix-study: effects of pioglitazone/metformin fixed combination in comparison with a combination of metformin with glimepiride on diabetic dyslipidemia. Diabetes Technol Ther. 2011 Jun;13(6):637-43. doi: 10.1089/dia.2010.0233. Epub 2011 Apr 2.