Effects of pentoxifylline on proteinuria and glucose control in patients with type 2 diabetes: a prospective randomized double-blind multicenter study

BACKGROUND Pentoxifylline is a methylxanthine derivative with significant anti-inflammatory, anti-fibrotic, and anti-proliferative properties. Studies have shown that pentoxifylline may have renoprotective effects in patients with diabetic nephropathy. However, most of these studies were limited by small sample sizes. Therefore, we investigated whether pentoxifylline could reduce proteinuria in patients with diabetic nephropathy and residual proteinuria who received an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB). We also studied the effects of pentoxifylline on glycemic control, insulin resistance, and inflammatory parameters. METHODS This was a prospective, randomized double-blind, placebo-controlled, multi-center study. A total of 174 patients with type 2 diabetes and albuminuria (>30 mg/g of creatinine) who were taking the recommended dosage of ACEI or ARB for > 6 months and receiving conventional therapy for diabetes were randomly assigned to receive pentoxifylline (1200 mg, daily; n = 87) or a placebo (n = 87) for 6 months. The endpoints were the effects of pentoxifylline on proteinuria, renal function, glucose control, and inflammatory parameters. RESULTS The percentage changes in proteinuria from baseline in the pentoxifylline and placebo groups were a decrease of 23 % and 4 %, respectively (p = 0.012). In addition, significant reductions in fasting plasma glucose, glycated hemoglobin, and insulin resistance according to the homeostasis model assessment were observed in the pentoxifylline group compared to those in the placebo group. However there was no significant difference in serum tumor necrosis factor (TNF)-α between the groups. CONCLUSIONS Pentoxifylline therapy reduced proteinuria and improved glucose control and insulin resistance without significant change of serum TNF-α in patients with type 2 diabetic nephropathy. Therefore, pentoxifylline is a potential therapeutic alternative for treating diabetes and diabetic nephropathy. TRIAL REGISTRATION NCT01382303.