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

Study Overview
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Brief Summary
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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. A total of 38 women with documented Type 2 Diabetes and menopause will be enrolled. The active treatment will include a 50 mg dose of vildagliptin OD twice a day. As comparator, gliclazide MR will be administered at a dose of 60 to 120 mg OD once a day.

Detailed Description
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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.

Official Title
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Effect of Anti-diabetic Drugs on Bone Metabolism and Glycemic Variability.A Comparison Between Vildagliptin and Gliclazide MR

Conditions
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Type 2 Diabetes Mellitus, Menopause, Osteoporosis, Osteopenia

Intervention / Treatment
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* Drug: Vildagliptin
* Drug: Gliclazide MR


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

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 |
| --- | --- |
| Experimental: Vildagliptin<br>Vildagliptin 50 mg bid for 12 months | Drug: Vildagliptin<br>* Vildagliptin 50mg bid orally for 12 months<br>* Other names: Galvus;|
| Active Comparator: Gliclazide MR<br>Gliclazide MR 60 or 120mg once a day for 12 months | Drug: Gliclazide MR<br>* Gliclazide MR 60 or 120mg orally for 12 months<br>* Other names: Diamicron MR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Markers of bone remodeling | Primary outcome is to compare the effect of vildagliptin with gliclazide MR on markers of bone remodeling. The outcome variables are the blood levels of: Osteocalcin (OC) Bone-specific alkaline phosphatase (BALP) Carboxy-terminal telopeptide of type I collagen (CTX) Amino-terminal telopeptide of type I collagen (NTX) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone mineral density of lumbar spine and femur by X-ray absorptiometry | To compare the effect of vildagliptin with gliclazide MR on bone mineral density of lumbar spine and femur by X-ray absorptiometry after 12-month treatment. | 12 months | 
| Glycemic variability | To compare the effect of vildagliptin with gliclazide MR on glycemic variability measured by MAGE method (mean amplitude of glycemic excursion) using a continuous glucose monitoring system | 6 months | 
| Calcitonin | Dosage of serum calcitonin | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NTX, BALP, diabetes, type 2 diabetes mellitus, osteopenia, osteoporosis, glycemic variability, bone markers, osteocalcin, CTX