24-Hour Glycemia: Rosiglitazone Versus Glimepiride In Type 2 Diabetes

Study Overview
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Brief Summary
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A better glycemic control is associated with less complications (cardiac diseases, blindness, etcetera) for type 2 diabetic patients. The objective is to study if rosiglitazone may lead to a more regular glycemic pattern with less hyperglycemia and hypoglycemia episodes than with a sulphonylurea (glimepiride).

Official Title
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Comparison of the Effects of Rosiglitazone and Glimepiride, Both Given in Combination With Metformin, on 24-Hour Glycemia in Type 2 Diabetes Patients Not Controlled With Metformin Alone. A 3-Month Multicentre, Randomized, Parallel-Group, Open-Label Study.

Conditions
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Non-Insulin-Dependent Diabetes Mellitus

Intervention / Treatment
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* Drug: rosiglitazone-metformin fixed dose combination
* Drug: metformin + glimepiride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged 40 to 80 years Diagnosis of type 2 diabetes mellitus for at least 6 months Body mass index (BMI) ≥25kg/m2 7%≥HbA1c ≤ 9% at visit 2 Treatment with metformin between 1.7g/day and 3g/day for at least 12 weeks prior to visit 1 Female subjects must be non-pregnant, post-menopausal, surgically sterile or using effective contraceptive measures Written informed consent Exclusion Criteria: Use of any oral antidiabetic drug other than metformin within 12 weeks prior to screening Significant hypersensitivity to thiazolidinediones and sulfonylureas or compounds with similar chemical structure Subjects who have required the use of insulin for glycaemic control at any time in the past or subject with a history of metabolic acidosis including diabetic ketoacidosis Subjects with clinically significant ongoing oedema or with a history of oedema in the 12 months prior to visit 1 Subjects with a history of severe hypoglycaemia Anemia defined by haemoglobin concentration <11.0g/dL for males or <10.0g/dL for females Renal disease or renal dysfunction, e.g. as suggested by serum creatinine levels ≥135µmol/L in males and ≥110µmol/L in females Presence of clinically significant hepatic disease (i.e. ALT, AST, total bilirubin or alkaline phosphatase >2.5 times the upper limit of the normal reference range) Congestive heart failure (NYHA class I to IV), unstable or severe angina, recent myocardial infarction Subjects with chronic diseases requiring periodic or intermittent treatment with oral or intravenous corticosteroids Female who are lactating, pregnant, or planning to become pregnant Any clinically significant abnormality identified at screening which in the judgement of the investigator makes the subject unsuitable for inclusion in the study (e.g. physical examination, laboratory test, ECG, ...) Use of any investigational agent within 30 days or 5 half-lives (whichever is longer) prior to enrolment in this study Active alcohol, drug or medication abuse within the last 6 months or any condition that would indicate the likelihood of poor subject compliance Subjects not willing to comply with the procedures described in this protocol.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: rosiglitazone-metformin fixed dose combination|nan|
|Drug: metformin + glimepiride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Hyperglycaemia (>126 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment | Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations. | Baseline and 12 weeks | 
| Episodes of Hyperglycaemia (>126 mg/dL) at Baseline Compared to After 12 Weeks on Treatment | Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Severe Hyperglycaemia (>150 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment | Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations. | Baseline and 12 weeks | 
| Episodes of Severe Hyperglycaemia (>150 mg/dL) at Baseline Compared to After 12 Weeks on Treatment | Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations. | Baseline and 12 weeks | 
| Duration of Hypoglycaemia (<80 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment | Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations. | Baseline and 12 weeks | 
| Episodes of Hypoglycaemia (<80 mg/dL) at Baseline Compared to After 12 Weeks on Treatment | Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations. | Baseline and 12 weeks | 
| Duration of Hypoglycaemia (<60 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment | Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations. | Baseline and 12 weeks | 
| Episodes of Hypoglycaemia (<60 mg/dL) at Baseline Compared to After 12 Weeks on Treatment | Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations. | Baseline and 12 weeks | 
| HbA1c (Glycosylated Hemoglobin) | Uncontrolled HbA1c>8.5%. HbA1c and fasting blood glucose taken at hospital | Baseline and 12 weeks | 
| 8-Iso Prostaglandin F2α (8-iso PGF2α) Excretion Rate | 8-Iso Prostaglandin F2α (8-iso PGF2α) excretion rate measured during the 24 hours preceding the CGM system removal. The nocturnal glycemia measured by CGM system will be defined as the average of glycemic values collected between midnight and breakfast time. | Baseline and 12 weeks | 
| Glycaemia According to CGMS (Nocturnal), mg/dL | Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.The nocturnal glycemia measured by CGM system will be defined as the average of glycemic values collected between midnight and breakfast time. | Baseline and 12 weeks | 
| Glycaemia According to CGMS (Diurnal), mg/dL | Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.The diurnal glycemia measured by CGM system will be the average of glycemic values recorded between breakfast time and midnight. | Baseline and 12 weeks | 
| Glycaemia According to CGMS (Dawn), mg/dL | Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.The glycemia at dawn measured by CGM system will be defined as the average of glycemic values recorded between 4 AM and breakfast time. | Baseline and 12 weeks | 
| Glycaemia According to CGMS (Total Area Under the Curve (AUC) for Values Above 1 mg/dL), mg/dL | Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations. The concentrations of glucose will be assessed from the AUC calculations on glycaemic values measured by CGM system. | Baseline and 12 weeks | 
| Glycaemia According to CGMS (Postprandial Incremental AUC or Values Above 1 mg/dL), mg/dL | Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations. The concentrations of glucose will be assessed from the AUC calculations on glycaemic values measured by CGM system. | Baseline and 12 weeks | 
| Glycaemia According to CGMS (Basal Incremental AUC or Values Above 1 mg/dL), mg/dL | Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations. The concentrations of glucose will be assessed from the AUC calculations on glycaemic values measured by CGM system. | Baseline and 12 weeks | 
| Glycaemia According to CGMS (MAGE), mg/dL | Calculation of the Mean amplitude of glycemic excursion (MAGE) was obtained by measuring the arithmetic mean of the major glucose concentration increases or decreases on days 2 and 3 of glycaemic profile and then averaging results on the two days. | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 2 diabetes, rosiglitazone, metformin, glimepiride, glycemia