Effect of Pioglitazone Versus Metformin on Bone Health in Postmenopausal Women With Type 2 Diabetes
The study tests whether pioglitazone (PIO)as compared to metformin (MET)affects bone health including bone mineral density, bone turnover markers, and osteocyte biomarker in patients with type 2 diabetes (T2DM).
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Phase 1 Study of Pioglitazone Versus Metformin on Bone Health in Postmenopausal Women With Type 2 Diabetes|
- Change in mean percentage change in BMD at various sites by Dual energy X-ray absorptiometry(DXA) from baseline and at 6, 12 months in PIO versus MET treatment group. [ Time Frame: 6-18 months ] [ Designated as safety issue: Yes ]The primary endpoint was change in mean percentage change in BMD values at the lumbar spine (L1-L4), femoral neck and total hip by DXA from baseline and at 6 and 12 months in the PIO and the MET treatment groups.
- Bone turnover Markers and other Biomarkers [ Time Frame: 6-18 months ] [ Designated as safety issue: Yes ]Secondary end-points were changes in serum sclerostin, serum bone-specific alkaline phosphatase (BSAP), serum procollagen type1 N-terminal propeptide (P1NP) and serum C-terminal crosslinking telopeptide of type 1 collagen (CTX); and urinary N-terminal crosslinking telopeptide type 1 collagen (u-NTX); serum calcium, 25-hydroxyvitamin D (25-OHD), and serum Dickkopf-1( DKK-1) at various time intervals from baseline between PIO vs MET treatment.
- Exploratory and Safety Outcomes [ Time Frame: 6-18 months ] [ Designated as safety issue: Yes ]Other endpoints were changes in inflammatory markers (hs-CRP)
- Exploratory Outcomes: lipid profile [ Time Frame: 6-18 months ] [ Designated as safety issue: Yes ]lipid profile (total cholesterol, HDL-c, LDL-c and triglycerides)
- Exploratory outcomes: liver and renal function tests [ Time Frame: 6-18 months ] [ Designated as safety issue: Yes ]liver function tests [albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)]; renal function tests (creatinine, urea, uric acid) and parathyroid hormone (PTH).
- Exploratory outcomes: glycemic control [ Time Frame: 6-18 months ] [ Designated as safety issue: Yes ]within and between treatment group comparisons of change from baseline at specified time points in HbA1c, fasting plasma glucose (FPG), fasting plasma insulin, and insulin sensitivity measured by the homeostasis model assessment (HOMA-s).
- Exploratory and safety outcomes [ Time Frame: 6-18 months ] [ Designated as safety issue: Yes ]Safety endpoints were adverse events (AEs), clinical laboratory assessments, vital signs, and electrocardiograms
|Study Start Date:||January 2009|
|Study Completion Date:||January 2014|
|Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Experimental: Experimental: 1
Pioglitazone given 30mg/once daily for 12 months.
30 mg/daily for 12 months
Other Name: Actos
Active Comparator: Active comparator: 2
Metformin given 850 mg/twice daily for 12 months.
850 mg/daily for 12 months
Other Name: Glucophage
Women with T2DM exhibit normal or higher bone mineral density (BMD) for their age, but with approximately twice the overall risk of bone fragility compared with nondiabetic subjects. Known the apparent association between T2DM and the risk of bone fragility, examining the effects of commonly used oral antidiabetic agents; such as MET and thiazolidinediones (TZDs; for example rosiglitazone [ROS] or PIO), on BMD and/or bone turnover is of great clinical relevance for both diabetic patients and their treating physicians. Recent clinical trials, showed that women treated with ROS had higher risk of bone fragility and self-reported adverse events. Similarly, women on long-term treatment with PIO for T2DM experienced higher incidence of distal extremity fractures. TZDs are agonists of the nuclear transcription factor peroxisome proliferator- activated receptor-γ (PPAR-γ) which increase insulin sensitivity and improve glycemic control in T2DM. PPAR (γ) acts also as a molecular factor that favours adipogenesis over osteoblastogenesis of mesenchymal stem cells. The latter was suggested as a potential mechanism for the effects of TZDs on bone among others. In humans, TZDs decrease BMD and increase bone fragility risk. This study tests whether pioglitazone as compared to MET (both are commonly used in the treatment of T2DM in Saudi Arabia and other countries) affects bone health including bone mineral density, bone turnover markers, and osteocyte biomarker in patients with T2DM.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01935804
|Center of Excellence for Osteoporosis Research, King Abdulaziz University|
|Jeddah, Makkah, Saudi Arabia, 21589|
|Principal Investigator:||Mohammed-Salleh M Ardawi, PhD, FRCPath||Center of Excellence for Osteoporosis Research and Faculty of Medicine, King Abdulaziz University|
|Study Director:||Abdulrahim A Rouzi, FRCPC||Center of Excellence for Osteoporosis Research, and Faculty of Medicine, King Abdulaziz University|