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

• ClinicalTrials.gov Identifier: NCT00318656
• Recruitment Status: Completed
• First Posted: April 27, 2006
• Results First Posted: March 18, 2009
• Last Update Posted: May 7, 2009
• Sponsor: GlaxoSmithKline
• Information provided by: GlaxoSmithKline

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Non-Insulin-Dependent Diabetes Mellitus	Drug: rosiglitazone-metformin fixed dose combination; Drug: metformin + glimepiride	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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.
• Study Start Date: November 2005
• Actual Primary Completion Date: October 2007
• Actual Study Completion Date: October 2007

Arms and Interventions

Intervention Details:

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Duration of Severe Hyperglycaemia (>150 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment [ Time Frame: Baseline and 12 weeks ]
   Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
2. Episodes of Severe Hyperglycaemia (>150 mg/dL) at Baseline Compared to After 12 Weeks on Treatment [ Time Frame: Baseline and 12 weeks ]
   Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
3. Duration of Hypoglycaemia (<80 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment [ Time Frame: Baseline and 12 weeks ]
   Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
4. Episodes of Hypoglycaemia (<80 mg/dL) at Baseline Compared to After 12 Weeks on Treatment [ Time Frame: Baseline and 12 weeks ]
   Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
5. Duration of Hypoglycaemia (<60 mg/dL) in Hours at Baseline Compared to After 12 Weeks on Treatment [ Time Frame: Baseline and 12 weeks ]
   Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
6. Episodes of Hypoglycaemia (<60 mg/dL) at Baseline Compared to After 12 Weeks on Treatment [ Time Frame: Baseline and 12 weeks ]
   Continuous Glycemic Monitoring System, Medtronic (CGMS®) System Gold downloads data to a computer for evaluation of glucose variations.
7. HbA1c (Glycosylated Hemoglobin) [ Time Frame: Baseline and 12 weeks ]
   Uncontrolled HbA1c>8.5%. HbA1c and fasting blood glucose taken at hospital
8. 8-Iso Prostaglandin F2α (8-iso PGF2α) Excretion Rate [ Time Frame: Baseline and 12 weeks ]
   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.
9. Glycaemia According to CGMS (Nocturnal), mg/dL [ Time Frame: Baseline and 12 weeks ]
   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.
10. Glycaemia According to CGMS (Diurnal), mg/dL [ Time Frame: Baseline and 12 weeks ]
    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.
11. Glycaemia According to CGMS (Dawn), mg/dL [ Time Frame: Baseline and 12 weeks ]
    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.
12. Glycaemia According to CGMS (Total Area Under the Curve (AUC) for Values Above 1 mg/dL), mg/dL [ Time Frame: Baseline and 12 weeks ]
    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.
13. Glycaemia According to CGMS (Postprandial Incremental AUC or Values Above 1 mg/dL), mg/dL [ Time Frame: Baseline and 12 weeks ]
    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.
14. Glycaemia According to CGMS (Basal Incremental AUC or Values Above 1 mg/dL), mg/dL [ Time Frame: Baseline and 12 weeks ]
    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.
15. Glycaemia According to CGMS (MAGE), mg/dL [ Time Frame: Baseline and 12 weeks ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, MD; GlaxoSmithKline

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Monnier L, Colette C, Comenducci A, Vallée D, Dejager S. Add-on therapies to metformin in type 2 diabetes: what modulates the respective decrements in postprandial and basal glucose? Diabetes Technol Ther. 2012 Oct;14(10):943-50. Epub 2012 Jul 9.

• Responsible Party: Study Director, GSK
• ClinicalTrials.gov Identifier: NCT00318656
• Other Study ID Numbers: 104988; AVAF4003
• First Posted: April 27, 2006
• Results First Posted: March 18, 2009
• Last Update Posted: May 7, 2009
• Last Verified: April 2009

Keywords provided by GlaxoSmithKline:

type 2 diabetes; rosiglitazone; metformin; glimepiride; glycemia

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Metformin; Glimepiride; Rosiglitazone; Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Immunosuppressive Agents; Immunologic Factors