Effect of Anti-diabetic Drugs on Bone Metabolism and Glycemic Variability

This is a Monocentric, Prospective, Randomized, Open-label, Comparative, Phase IV Study, to compare the effects of Vildagliptin and Gliclazide MR on Markers of Bone Remodeling, Bone Mineral Density and Glycemic Variability in Postmenopausal Women with Type 2 Diabetes.

Target population of clinical trial subjects A total of 38 women with documented Type 2 Diabetes and menopause will be enrolled. To be as close to a real life scenario as possible, clinical trial subjects which are treated with glucose-lowering medication (except incretin or sulfonylurea based therapies) and treatment-naive subjects will be included.

Investigational Product, posology and method of administration The active treatment will include a 50 mg dose of vildagliptin OD twice a day.

Comparator, posology and method of administration As comparator, gliclazide MR will be administered at a dose of 60 to 120 mg OD once a day.

Treatment duration The study will have an expected total duration of 18 months, 12 months of active treatment.

Inclusion criteria

• 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.
• All study subjects must be women diagnosed with type 2 diabetes based on current guidelines of Sociedade Brasileira de Diabetes (SBD - Brazilian Society of Diabetes) and/or American Society of Diabetes (ADA) and they should have all the following criteria:

• Age ≥ 40 years old.
• HbA1c ≥ 6.5% at randomization.
• Menopause defined as:
• Absence of menstruation for at least 12 months in patients with an intact uterus, or
• FSH level greater than 30 mIU/mL in a hysterectomized patient and/or,
• FSH level greater than 30 mIU/mL in a patient with surgical menopause.

Exclusion criteria

• Acute vascular event (cardiac, cerebral or peripheral) for at least 2 months of randomization.
• Patient on chronic dialysis and/or renal transplantation and/or serum creatinine > 1.5 mg/dL.
• Patients with HIV, severe autoimmune disease or chronic treatment with oral steroids (> 30 consecutive days).
• Current or previous treatment (within 6 months) with incretin (DPP-IV inhibitor or GLP-1 analog) within 6 months prior to randomization.
• Current or previous treatment with pioglitazone or rosiglitazone within 12 months prior to randomization.
• Sustained arterial hypertension > 180/100 mm Hg.
• Body mass index (BMI) > 50 kg/m².
• HbA1c ≥ 9,5% at randomization.
• Transaminases (AST (SGOT) and ALT (SGPT)) > 2.5 x upper limit of normal.
• Chronic liver disease or alcoholic liver disease.
• LDL-cholesterol > 250 mg/dL (> 6.48 mmol/L).
• Triglycerides > 1000 mg/dL (> 11.3 mmol/L).
• HDL-cholesterol < 25 mg/dL (< 0.64 mmol/L).
• Levels of 25-OH-vitamin D < 20ng/mL at randomization
• Abnormal levels of PTH, cortisol, IGF-1 or GH at randomization
• Prescription of any investigational medication within one year before the screening visit (visit 1), unless there is a direct benefit to the study subject, at the discretion of the investigator.
• History of previous fracture
• Pregnant or breastfeeding patients.
• Previous participation on this study.
• Individuals at risk for poor adherence to the protocol or medication.
• Any condition that makes the patient unable to complete the study within 12 months.