Effect of Anti-diabetic Drugs on Glycemic Variability

• Status: Completed
• Trial end date: 2019-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Objectives

Primary objective:

To access the change from baseline to week 12 in MAGE index of glycemic variability measured by CGMS for dapagliflozin versus. gliclazide MR.

Secondary objectives:

1. Change from baseline to week 12 in glycated hemoglobin A1c (HbA1c), fasting plasma glucose, postprandial glucose and achievement of HbA1c ≤6.5% and <7% at the end of the study) for dapagliflozin versus gliclazide MR.

2. Change from baseline to week 12 in glycemic variability defined by the interquartile range (IQR - interval between 25th and 75th percentiles) measured by CGMS for dapagliflozin versus gliclazide MR.

3. Change from baseline to week 12 in glycemic variability measured by the Standard Deviation of the mean glycemia (SD) measured by CGMS for dapagliflozin versus gliclazide MR.

4. Change from baseline to week 12 in glycemic variability measured by the Coefficient of Variation (CV) measured by CGMS for dapagliflozin versus gliclazide MR.

5. Change from baseline to week 12 in the time spent on hypoglycemic range (glycemia <70mg/dL) measured by CGMS for dapagliflozin versus gliclazide MR.

Study design This is a single-center, prospective, randomized, open-label, comparative, phase IV study to compare the effects of gliclazide MR and dapagliflozin on Glycemic Variability in patients with Type 2 Diabetes Mellitus (T2DM). All patients should be treatment naïve or receive standard of care therapy for T2DM as well as for co-morbidities based on accepted guidelines and local best practices.

Target patient population Approximately 120 patients with T2DM will be randomized from study site. Patients who were treated with metformin only and had inadequate glycemic control at the time of enrollment as well as treatment naïve or non-medically treated (e.g., diet) patients, will be enrolled and receive either dapagliflozin 10mg qd or comparator gliclazide MR 120mg qd in addition to standard of care treatment for T2DM and co-morbidities.

Investigational product, dosage and mode of administration Dapagliflozin 10mg tablets administered orally once daily for 12 weeks.

Comparator, dosage and mode of administration Gliclazide MR 60mg tablets administered orally, 2 tablets once daily for 12 weeks.

Duration of treatment The treatment with study medication or comparator will have a total duration of 15 weeks.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centro de Diabetes Curitiba Ltda
• Collaborator: AstraZeneca
• Treatments: Dapagliflozin; Gliclazide; Hypoglycemic Agents

Criteria

Inclusion Criteria:

A. Informed consent form obtained before any study-related activity. Study-related activities are any procedure that would not be performed during the normal treatment of the patient.

B. All study subjects must be patients diagnosed with type 2 diabetes based on current guidelines of Brazilian Society of Diabetes and/or American Diabetes Association (ADA) and they should have all the following criteria:

• Age ≥40 years old.

• HbA1c ≥7% at randomization.

• Drug naïve or metformin treated with a stable dose for at least 3 months.

Exclusion Criteria:

1. Acute vascular event (cardiac, cerebral or peripheral) for at least 2 months of randomization.

2. Patient on chronic dialysis and/or renal transplantation and/or serum creatinine >1.5 mg/dL and/or estimated glomerular filtration rate (eGFR) < 45ml/min (MDRD) and/or Creatinine Clearance <60ml/min.

3. Patients with HIV, severe autoimmune disease or chronic treatment with oral steroids (>30 consecutive days).

4. Current or previous treatment with any SGLT-2 inhibitor within 2 months prior to randomization.

5. Current or previous treatment with any type of insulin within 2 months prior to randomization.

6. Current or previous treatment with any sulphonylurea and meglitinide within 2 months prior to randomization.

7. Current or previous treatment with any DPP-4 inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist within 2 months prior to randomization.

8. Current or previous treatment with acarbose within 2 months prior to randomization.

9. Sustained arterial hypertension ≥160/100mm Hg.

10. Body mass index (BMI) >50 kg/m².

11. HbA1c ≥10.5% at randomization.

12. Transaminases (aspartate aminotransferase and/or alanine aminotransferase) >2.5 x upper limit of normal.

13. Total bilirubin >2.5 x upper limit of normal

14. Chronic liver disease or alcoholic liver disease.

15. LDL-cholesterol >250 mg/dL (>6.48 mmol/L).

16. Triglycerides >1000 mg/dL (>11.3 mmol/L).

17. HDL-cholesterol <25 mg/dL (<0.64 mmol/L).

18. Positive haematuria observed in urine sample obtained in the run-in visit.

19. Prescription of any investigational medication within 3 months before the screening visit.

20. Prescription of any investigational medication within the period between 3 months and one year before the screening visit (visit 1), unless there is a direct benefit to the study subject, at the discretion of the investigator.

21. Pregnant or breastfeeding patients.

22. Previous participation on this study.

23. Individuals at risk for poor adherence to the protocol or medication.

24. Any condition that makes the patient unable to complete the study within 3 months.