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

• Duration of Hyperglycaemia (>126 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• Episodes of Hyperglycaemia (>126 mg/dL) at Baseline Compared to After 12 Weeks on Treatment [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]

• Duration of Severe Hyperglycaemia (>150 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• Episodes of Severe Hyperglycaemia (>150 mg/dL) at Baseline Compared to After 12 Weeks on Treatment [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• Duration of Hypoglycaemia (<80 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• Episodes of Hypoglycaemia (<80 mg/dL) at Baseline Compared to After 12 Weeks on Treatment [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• Duration of Hypoglycaemia (<60 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• Episodes of Hypoglycaemia (<60 mg/dL) at Baseline Compared to After 12 Weeks on Treatment [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• HbA1c (Glycosylated Hemoglobin) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• 8-Iso Prostaglandin F2α (8-Iso PGF2α) Excretion Rate [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• Glycaemia According to CGMS (Nocturnal), mg/dL [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• Glycaemia According to CGMS (Diurnal), mg/dL [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• Glycaemia According to CGMS (Dawn), mg/dL [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• Glycaemia According to CGMS (Total Area Under the Curve (AUC) for Values Above 1 mg/dL), mg/dL [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• Glycaemia According to CGMS (Postprandial Incremental AUC or Values Above 1 mg/dL), mg/dL [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• Glycaemia According to CGMS (Basal Incremental AUC or Values Above 1 mg/dL), mg/dL [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• Glycaemia According to CGMS (MAGE), mg/dL [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]

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).

• Drug: rosiglitazone-metformin fixed dose combination
• Drug: metformin + glimepiride
  Other Names:

  • rosiglitazone-metformin fixed dose combination
  • metformin + glimepiride

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.