Effect of Pioglitazone Versus Metformin on Bone Health in Postmenopausal Women With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

— Pioglitazone  

Official title:

Phase 1 Study of Pioglitazone Versus Metformin on Bone Health in Postmenopausal Women With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01935804
• Other study ID #: CEOR-01-08
• Status: Completed
• Phase: Phase 2
• First received: August 27, 2013
• Last updated: June 16, 2014
• Start date: January 2009
• Est. completion date: January 2014

Study information

• Verified date: June 2014
• Source: King Abdulaziz University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Saudi Arabia: Ministry for Higher Education
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 440
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 50 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Glucose Metabolism Disorders
• Metabolic Diseases

Intervention

Drug:
• Pioglitazone
30 mg/daily for 12 months
• Metformin
850 mg/daily for 12 months

Locations

Country	Name	City	State
Saudi Arabia	Center of Excellence for Osteoporosis Research, King Abdulaziz University	Jeddah	Makkah

Sponsors (1)

Lead Sponsor	Collaborator
King Abdulaziz University

Country where clinical trial is conducted

Saudi Arabia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory and Safety Outcomes	Other endpoints were changes in inflammatory markers (hs-CRP)	6-18 months	Yes
Other	Exploratory Outcomes: lipid profile	lipid profile (total cholesterol, HDL-c, LDL-c and triglycerides)	6-18 months	Yes
Other	Exploratory outcomes: liver and renal function tests	liver function tests [albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)]; renal function tests (creatinine, urea, uric acid) and parathyroid hormone (PTH).	6-18 months	Yes
Other	Exploratory outcomes: glycemic control	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).	6-18 months	Yes
Other	Exploratory and safety outcomes	Safety endpoints were adverse events (AEs), clinical laboratory assessments, vital signs, and electrocardiograms	6-18 months	Yes
Primary	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.	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.	6-18 months	Yes
Secondary	Bone turnover Markers and other Biomarkers	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.	6-18 months	Yes