Safety and efficacy of low dose pioglitazone compared with standard dose pioglitazone in type 2 diabetes with chronic kidney disease: A randomized controlled trial

Background
Choices of hypoglycemic agents for patients with type 2 diabetes and chronic kidney disease (CKD) are limited. Available data among patients with CKD suggest that pioglitazone was effective and safe, with no increase in serious adverse effects. However, weight gain and fluid retention are major clinical problems for pioglitazone among patients with CKD. We conducted this study to compare the efficacy and side effects of low dose pioglitazone with standard dose pioglitazone among patients with type 2 diabetes and CKD.
Methods
A total of 75 patients with type 2 diabetes and CKD and inadequate glycemic control receiving any pharmacological antidiabetic treatment were randomly assigned to 2 groups. One group consisted of 37 patients treated with standard dose pioglitazone (15 mg/day) and another group consisted of 38 patients treated with low dose pioglitazone (7.5 mg/day). Glycosylated hemoglobinA1c (HbA1c) and metabolic profiles were monitored every 8 weeks for 24 weeks. Body composition was assessed using bio-electrical impedance analysis (BIA).
Results
After 6 months of therapy, HbA1c levels decreased in both standard and low dose pioglitazone groups. The mean changes in HbA1c for standard and low dose pioglitazone were 1.1±1.6 and -1.4±1.5 (P = 0.543), respectively. Compared with low dose pioglitazone, standard dose pioglitazone treatment led to a greater increase in body weight, fat mass, total body water and extracellular water composition. No major adverse effects including hypoglycemia, congestive heart failure and abnormal liver function were identified.
Conclusion
Pioglitazone 7.5 mg once daily treatments presented similar glycemic control to standard dose pioglitazone and exhibited beneficial effects on weight gain and fluid retention among patients with type 2 diabetes and CKD.

研究背景
针对2型糖尿病合并慢性肾脏病（chronic kidney disease, CKD）患者的降糖药物选择十分有限。现有针对CKD患者的研究数据表明，吡格列酮（pioglitazone）安全有效，未增加严重不良反应的发生风险。然而，体重增加与体液潴留是CKD患者使用吡格列酮时面临的主要临床问题。本研究旨在对比低剂量吡格列酮与标准剂量吡格列酮在2型糖尿病合并CKD患者中的疗效与不良反应。

研究方法
本研究共纳入75例血糖控制不佳且曾接受降糖药物治疗的2型糖尿病合并CKD患者，将其随机分为两组。其中标准剂量组37例，予以15mg/日的标准剂量吡格列酮治疗；低剂量组38例，予以7.5mg/日的低剂量吡格列酮治疗。在24周的随访周期内，每8周检测一次糖化血红蛋白（glycosylated hemoglobin A1c, HbA1c）与代谢指标，并采用生物电阻抗分析法（bio-electrical impedance analysis, BIA）评估身体成分。

研究结果
治疗6个月后，标准剂量组与低剂量组的HbA1c水平均有所下降。标准剂量组与低剂量组的HbA1c平均变化值分别为1.1±1.6与-1.4±1.5（P=0.543）。与低剂量吡格列酮相比，标准剂量吡格列酮治疗可导致体重、脂肪量、总体水及细胞外水成分出现更显著的升高。两组均未观察到包括低血糖、充血性心力衰竭及肝功能异常在内的严重不良反应。

研究结论
每日一次7.5mg吡格列酮治疗方案，在2型糖尿病合并CKD患者中可实现与标准剂量吡格列酮相当的血糖控制效果，且在体重增加与体液潴留方面展现出更优的临床获益。