Clinical trial NCT01935804: Effect of Pioglitazone Versus Metformin on Bone Health in Postmenopausal Women With Type 2 Diabetes
Official title: Phase 1 Study of Pioglitazone Versus Metformin on Bone Health in Postmenopausal Women With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Keywords: pioglitazone
metformin
hyperglycemic agents
physiological effects of drugs
bone health
Lead sponsor: King Abdulaziz University
Sponsor class: OTHER
First posted: 2013-09-05
Enrollment: 440
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* BMD T-score greater than -2.5 at the total hip, femoral neck, and lumbar spine;
* No prior antidiabetic therapy;
* Drug-naïve with glycosylated hemoglobin A1c (HbA1c) ≥ 7.0 to ≤ 10.0%. 53.2 mmol/mol to 88.2 mmol/mol);
* Body-mass index of 40 Kg/m2 and less;
* Stable body weight for at least 4 months.

Exclusion Criteria:

* Type 1 diabetes mellitus (presence of GAD auto antibodies);
* History of diabetes or uncontrolled hypertension;
* Treatment with antidiabetic agents including TZDs;
* Chronic diseases known to affect bone;
* Previous treatment with estrogens and other medications known to affect bone ;
* Creatinine clearance less than 60 ml/min

Primary outcomes:
measure: 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.
timeFrame: 6-18 months
Secondary outcomes:
measure: Bone turnover Markers and other Biomarkers
timeFrame: 6-18 months
Other outcomes:
measure: Exploratory and Safety Outcomes
timeFrame: 6-18 months
measure: Exploratory Outcomes: lipid profile
timeFrame: 6-18 months
measure: Exploratory outcomes: liver and renal function tests
timeFrame: 6-18 months
measure: Exploratory outcomes: glycemic control
timeFrame: 6-18 months
measure: Exploratory and safety outcomes
timeFrame: 6-18 months
Locations:
city: Jeddah
country: Saudi Arabia
facility: Center of Excellence for Osteoporosis Research, King Abdulaziz University
state: Makkah
Study officials:
affiliation: Center of Excellence for Osteoporosis Research and Faculty of Medicine, King Abdulaziz University
name: Mohammed-Salleh M Ardawi, PhD, FRCPath
role: PRINCIPAL_INVESTIGATOR
affiliation: Center of Excellence for Osteoporosis Research, and Faculty of Medicine, King Abdulaziz University
name: Abdulrahim A Rouzi, FRCPC
role: STUDY_DIRECTOR
References: