Clinical trial NCT01679899: Effect of Anti-diabetic Drugs on Bone Metabolism and Glycemic Variability
Official title: Effect of Anti-diabetic Drugs on Bone Metabolism and Glycemic Variability.A Comparison Between Vildagliptin and Gliclazide MR
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Menopause
Osteoporosis
Osteopenia
Keywords: diabetes
type 2 diabetes mellitus
osteopenia
osteoporosis
glycemic variability
bone markers
osteocalcin
NTX
CTX
BALP
Lead sponsor: Centro de Diabetes Curitiba Ltda
Sponsor class: OTHER
First posted: 2012-09-06
Enrollment: 56
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Markers of bone remodeling
timeFrame: 6 months
Secondary outcomes:
measure: Bone mineral density of lumbar spine and femur by X-ray absorptiometry
timeFrame: 12 months
measure: Glycemic variability
timeFrame: 6 months
measure: Calcitonin
timeFrame: 12 months
Other outcomes:
measure: Levels of aminotransferases
timeFrame: 6 months
Locations:
city: Curitiba
country: Brazil
facility: Centro de Diabetes Curitiba
state: Parana
Study officials:
affiliation: Centro de Diabetes Curitiba
name: Andre GD Vianna, MD
role: STUDY_CHAIR
References:
citation: Vianna AGD, de Lacerda CS, Pechmann LM, Polesel MG, Marino EC, Borba VZC, Barreto FC. Vildagliptin has the same safety profile as a sulfonylurea on bone metabolism and bone mineral density in post-menopausal women with type 2 diabetes: a randomized controlled trial. Diabetol Metab Syndr. 2017 May 15;9:35. doi: 10.1186/s13098-017-0232-2. eCollection 2017.