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

King Abdulaziz University

Status and phase: Completed; Phase 2

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

Treatments: Drug: Pioglitazone; Drug: Metformin

Study type: Interventional

Funder types: Other

Identifiers

NCT01935804

CEOR-01-08

Details and patient eligibility

About

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).

Full 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.

Enrollment: 440 estimated patients

Sex: Female

Ages: 50 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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440 participants in 2 patient groups

Experimental: 1

Experimental group

Description:

Pioglitazone given 30mg/once daily for 12 months.

Treatment:

Drug: Pioglitazone

Active comparator: 2

Active Comparator group

Description:

Metformin given 850 mg/twice daily for 12 months.

Treatment:

Drug: Metformin