Phase 3
N=305
Efficacy of Pioglitazone/Metformin Combination Therapy in Subjects With Type 2 Diabetes Mellitus and Dyslipidemia.
Diabetes Mellitus · Dyslipidemias
Bottom Line
View on ClinicalTrials.gov: NCT00770653 ↗Enrolled (actual)
305
Serious AEs
8.3%
Results posted
Oct 2010
Primary outcome: Primary: The Mean Increase From Baseline in High-Density Lipoprotein Cholesterol. — 3.2; -0.3 mg/dL — p=0.0018
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Pioglitazone and Metformin (Drug); Glimepiride and Metformin (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Takeda
- Primary completion
- May 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY The Mean Increase From Baseline in High-Density Lipoprotein Cholesterol. |
3.2; -0.3 | 0.0018 sig |
| SECONDARY Change From Baseline in High-Density Lipoprotein Cholesterol. |
3.3; -0.4 | 0.0018 sig |
| SECONDARY Change From Baseline in High-Density Lipoprotein/Low-Density Lipoprotein Ratio. |
0.1; 0.3 | 0.1167 |
| SECONDARY Change From Baseline in Triglycerides. |
-40.9; -16.7 | 0.1012 |
| SECONDARY Change From Baseline in Low-Density Lipoprotein Subfractions. |
6.2; 6.1 | 0.7486 |
| SECONDARY Change From Baseline in Low-Density Lipoprotein Cholesterol. |
9.7; 11.2 | 0.9464 |
| SECONDARY Change From Baseline in Glycosylated Hemoglobin. |
-0.83; -0.95 | 0.0807 |
| SECONDARY Change From Baseline in Fasting Intact Proinsulin. |
-5.18; -0.11 | <.0001 sig |
| SECONDARY Change From Baseline in Fasting Glucose. |
-21.6; -21.1 | 0.7799 |
| SECONDARY Change From Baseline in Adiponectin. |
6.79; 0.72 | <.0001 sig |
| SECONDARY Change From Baseline in High Sensitivity C-reactive Protein (Original). |
-0.21; -0.04 | 0.4131 |
| SECONDARY Change From Baseline in High Sensitivity C-reactive Protein (≤ 10 mg/L). |
-0.87; 0.00 | <.0001 sig |
| SECONDARY Change From Baseline in Systolic Blood Pressure. |
-2.5; 0.5 | 0.0929 |
| SECONDARY Change From Baseline in Diastolic Blood Pressure. |
-1.3; -0.1 | 0.3279 |
| SECONDARY Intake of Study Medication Greater Than 80% and Less Than 120%. |
136; 137 | 0.2895 |
| SECONDARY Change From Baseline in Nitrotyrosine. |
-2.7; 32.5 | 0.3517 |
| SECONDARY Change From Baseline in Soluble CD40 Ligand. |
-40.7; 102.4 | 0.1979 |
| SECONDARY Change From Baseline in Matrix Metallo Proteinase-9. |
31.4; 51.6 | 0.7186 |
| SECONDARY Change From Baseline in Soluble Intracellular Adhesion Molecule. |
-13.0; -3.2 | 0.5058 |
| SECONDARY Change From Baseline in Soluble Vascular Cell Adhesion Molecule. |
11.6; 3.3 | 0.5230 |
| SECONDARY Change From Baseline in Thromboxane B2. |
-216.4; 527.8 | 0.2203 |
| SECONDARY Change From Baseline in Platelet Function. |
-30.3; -1.0 | 0.5850 |
| SECONDARY Change From Baseline in E-Selectin. |
-3.7; -0.5 | 0.0138 sig |
| SECONDARY Change From Baseline in Von-Willebrand Factor. |
-19.5; 1.4 | 0.0817 |
| SECONDARY Change From Baseline in Erythrocyte Deformability (0.30%). |
1.3; -0.4 | 0.1761 |
| SECONDARY Change From Baseline in Erythrocyte Deformability (0.60%) |
2.4; -0.5 | 0.0002 sig |
| SECONDARY Change From Baseline in Erythrocyte Deformability (1.20). |
3.2; -1.1 | 0.0055 sig |
| SECONDARY Change From Baseline in Erythrocyte Deformability (3.00). |
3.3; -.15 | 0.0264 sig |
| SECONDARY Change From Baseline in Erythrocyte Deformability (6.00). |
3.1; -1.4 | 0.0509 |
| SECONDARY Change From Baseline in Erythrocyte Deformability (12.00). |
2.7; -1.3 | 0.1013 |
| SECONDARY Change From Baseline in Erythrocyte Deformability (30.00). |
2.5; -1.3 | 0.1363 |
| SECONDARY Change From Baseline in Erythrocyte Deformability (60.00). |
2.7; -1.3 | 0.1165 |
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.
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.
Data sourced from ClinicalTrials.gov (NCT00770653). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.