Background: Microalbuminuria is an early marker of diabetic nephropathy in type 2 diabetes mellitus (T2DM) which predicts the development of later stages of nephropathy. Thiazolidinediones are a class of oral hypoglycaemic drugs used in diabetes glycaemic management that act through PPARγ receptors. Studies have suggested they significantly reduce urinary albumin excretion; however, most trials were small. We therefore performed a systematic review to clarify the effectiveness of thiazolidinediones on microalbuminuria in adults with T2DM.
Methods: Eleven electronic databases were searched from inception to March 2007 and references from included trials were checked. Randomised, controlled trials were included if the patients had T2DM, were being treated with rosiglitazone or pioglitazone in comparison to other hypoglycaemic medication and had their urinary albumin excretion measured as either urinary albumin excretion rate (UAER) or urinary albumin creatinine ratio (UACR) at the study endpoint. Secondary outcomes were HbA1c, blood pressure, serum lipids and adverse events.
Results: Thirteen trials reporting on 3473 subjects were included in the systematic review and five studies were suitable for meta-analysis. Thiazolidinediones significantly reduced UAER at the study endpoint when compared to control, (pooled weighted mean difference (WMD) −69.52 μg/min; 95% CI, −78.61 to −60.44; P<0.00001). Twelve months therapy (WMD −103.66 μg/min; 95% CI −119.70 to −87.63 (P<0.00001)) was more effective than 36 months therapy (WMD −56.01 μg/min; 95% CI −65.24 to −46.79 (P<0.00001)). Qualitative analysis showed that in the majority of studies (75%), thiazolidinediones exerted a significant positive effect by reducing UACR.
Conclusions: This systematic review shows that thiazolidinediones sufficiently reduce urinary albumin excretion in patients with T2DM and suggests that they might be useful in preventing the progression of microalbuminuria to the later stages of diabetic nephropathy. The adverse side effect profile of the glitazones has been more emphasized in recent years and this potential benefit may be overlooked.