Glycemic Excursions in Type 2 Diabetic Patients With Vildagliptin and Metformin Versus Vildagliptin and Glimepiride

Study Overview
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Brief Summary
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The purpose of this study was to compare the effect of a fixed dose combination of vildagliptin plus metformin versus combination therapy of glimepiride plus metformin in glycemic variability in patients with type 2 diabetes who have not achieved adequate control of their disease prior to treatment with metformin monotherapy in optimal doses.

Official Title
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Glycemic Excursions in Type 2 Diabetic Patients Treated With Vildagliptin and Metformin (GalvusMet) Versus Glimepiride and Metformin

Conditions
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Type 2 Diabetes, Hypoglycemia

Intervention / Treatment
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* Drug: vildagliptin and metformin (combination)
* Drug: glimepiride
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: HbA1c between 8%-10.5% in stable metformin dose (>1500 mg/day), four weeks prior visit 1 Key Exclusion Criteria: Use of other antidiabetic oral therapy during the last 3 months (sulphonylurea, glitazones, GLP-1 analogues, DPP-4 inhibitors), except metformin

Ages Eligible for Study
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Minimum Age: 18 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: vildagliptin and metformin<br>Based on basal dose of metformin, administration of vildagliptin/metformin 50 mg/850 mg twice daily (bid) or 50 mg/1000 mg bid for 12 weeks | Drug: vildagliptin and metformin (combination)<br>* vildagliptin and metformin combination therapy as 50mg/850mg bid or 50mg/1000mg bid<br>|
| Active Comparator: glimepiride and metformin<br>Protocol specified dosage and frequency of glimepiride + metformin for 12 weeks based on basal dose of metformin | Drug: glimepiride<br> <br> Drug: Metformin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic Variability Measured by Mean Amplitude of Glucose Excursions (MAGE) | Mean Amplitude of Glycemic Excursions (MAGE) , which determines the average blood glucose excursions either above or below a value of one standard deviation of the average value of glucose in a given day. MAGE is calculated from the data of continuous tissue glucose monitoring obtained during the measurement period. MAGE is calculated with the formula Σ λ / χ if λ> ν (where λ = changes in blood glucose from peak to nadir, χ = number of valid observations, ν = 1 standard deviation of the mean glucose during a period of 24 hours) from the data of continuous monitoring of the tissue glucose, obtained during the period of measurement. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic Variability Measured by Continuous Overlapping Net Glycemic Action (CONGA) | Continuous Overlapping Net Glycemic Action (CONGA) which assesses intra-day glycemic variability by calculating the difference between values at different intervals, adjusted according to requirements with the advantage of being highly reproducible. CONGA is calculated in the conventional way with the formula √tқΣt = t1 (Dt -Ď2) / қ - 1, Ď = tқ Σ Dt t = t1 / қ, Dt = Gt-Gt-m (where қ = Observations with an observation n x 60 minutes, G = glucose measure) from the data of continuous monitoring of tissue glucose obtained during the measurement period. | Week 12 | 
| Glycemic Variability Measured by Total Standard Deviation (TSD) | Total standard deviation (TSD) or standard deviation of all values of a given measurement period, which has the advantage of being able to include all measured values on a given time period (even several days) through a common and simple statistical concept. TSD is calculated conventionally with the formula σ = √Σ (Xi - ῦ) 2 / N (where Xi represents each of the values, ῦ represents the population mean and N is the number of observations) from the data of continuous monitoring of tissue glucose obtained during the measurement. | Week 12 | 
| Percentage of Patients Who Achieved a Decrease Equal to or Greater Than 0.3% in Value of HbA1c at Week 12 |  | Screening visit , 12 weeks of treatment | 
| Change in HbA1c at Week 12 of Treatment in Comparison to HbA1c at Baseline |  | baseline, 12 weeks of treatment | 
| Number of Patients With Incidence of Hypoglycemia | Hypoglycemia defined as Glycemia < 70 mg/dl | 12 weeks | 
| Mean Amplitude of Glycemic Excursions (MAGE) for Patients With Hypoglycemia Incidence After 12 Weeks of Treatment | MAGE , which determines the average blood glucose excursions either above or below a value of one standard deviation of the average value of glucose in a given day. MAGE is calculated from the data of continuous tissue glucose monitoring obtained during the measurement period. MAGE is calculated with the formula Σ λ / χ if λ> ν (where λ = changes in blood glucose from peak to nadir, χ = number of valid observations, ν = 1 standard deviation of the mean glucose during a period of 24 hours) from the data of continuous monitoring of the tissue glucose, obtained during the period of measurement. In this endpoint, mean MAGE value is reported for hypo glycemic patients. | 12 weeks | 
| Number of Patients With Any Adverse Events, Serious Adverse Events and Death |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, hypoglycemia, glycemic variability, vildagliptin, glimepiride