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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypoglycemia; Type 2 Diabetes
• Intervention / Treatment: Drug: Metformin; Drug: glimepiride; Drug: vildagliptin and metformin (combination)

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Colombia
  • Bogotá, Colombia, 00000
    • Novartis Investigative Site
  • Cali, Colombia
    • Novartis Investigative Site
  • Monteria, Colombia
    • Novartis Investigative Site
  • Antioquia
    • Medellín, Antioquia, Colombia
      • Novartis Investigative Site
  • Caldas
    • Manizales, Caldas, Colombia, 1700
      • Novartis Investigative Site
  • Cundinamarca
    • Bogotá, Cundinamarca, Colombia
      • Novartis Investigative Site
    • Chía, Cundinamarca, Colombia, 11001000
      • Novartis Investigative Site
  • Valle del Cauca
    • Cali, Valle del Cauca, Colombia, 760001
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: vildagliptin and metformin; 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); vildagliptin and metformin combination therapy as 50mg/850mg bid or 50mg/1000mg bid
Active Comparator: glimepiride and metformin; Protocol specified dosage and frequency of glimepiride + metformin for 12 weeks based on basal dose of metformin	Drug: Metformin; Drug: glimepiride

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2014
• Primary Completion (Actual): February 22, 2016
• Study Completion (Actual): February 22, 2016

Study Registration Dates

• First Submitted: December 5, 2013
• First Submitted That Met QC Criteria: December 5, 2013
• First Posted (Estimate): December 10, 2013

Study Record Updates

• Last Update Posted (Actual): July 11, 2017
• Last Update Submitted That Met QC Criteria: April 13, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: diabetes; hypoglycemia; vildagliptin; glimepiride; glycemic variability
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Protease Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Glimepiride; Vildagliptin
• Other Study ID Numbers: CLAF237ACO01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No