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

NCT ID: NCT01935804

Last Updated: 2014-06-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 440 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2014-01-31

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.

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Experimental: 1

Pioglitazone given 30mg/once daily for 12 months.

Group Type: EXPERIMENTAL

Pioglitazone

Intervention Type: DRUG

30 mg/daily for 12 months

Active comparator: 2

Metformin given 850 mg/twice daily for 12 months.

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

850 mg/daily for 12 months

Interventions

Pioglitazone

30 mg/daily for 12 months

Intervention Type: DRUG

Metformin

850 mg/daily for 12 months

Intervention Type: DRUG

Other Intervention Names

Actos; Glucophage

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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

King Abdulaziz University

OTHER

Sponsor Role: lead

Responsible Party

Mohammed-Salleh M. Ardawi

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mohammed-Salleh M Ardawi, PhD, FRCPath

Role: PRINCIPAL_INVESTIGATOR

Center of Excellence for Osteoporosis Research and Faculty of Medicine, King Abdulaziz University

Abdulrahim A Rouzi, FRCPC

Role: STUDY_DIRECTOR

Center of Excellence for Osteoporosis Research, and Faculty of Medicine, King Abdulaziz University

Locations

Center of Excellence for Osteoporosis Research, King Abdulaziz University

Jeddah, Mecca Region, Saudi Arabia

Countries

Saudi Arabia

Other Identifiers

CEOR-01-08

Identifier Type: -

Identifier Source: org_study_id