Phase 1 Study of Pioglitazone Versus Metformin on Bone Health in Postmenopausal Women With Type 2 Diabetes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 440
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Experimental: 1
Pioglitazone given 30mg/once daily for 12 months.
干预措施: Pioglitazone (Drug)
Active comparator: 2
Metformin given 850 mg/twice daily for 12 months.
干预措施: Metformin (Drug)
结局指标
主要结局
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.
时间窗: 6-18 months
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.
次要结局
- Bone turnover Markers and other Biomarkers(6-18 months)
研究者
Mohammed-Salleh M. Ardawi
Professor
King Abdulaziz University