Comparison of the Effects of Pioglitazone versus Placebo when Given in Addition to Standard Insulin Treatment in Patients with Type 2 Diabetes Mellitus Requiring Hemodialysis: Results from the PIOren Study.

Background: Patients with type 2 diabetes mellitus and advanced kidney disease are usually treated with insulin. However, the prolonged pharmacokinetic insulin profile in patients with delayed renal insulin elimination impairs a successful therapy. Due to its hepatic metabolism, pioglitazone is a potential candidate for additional administration. The aim of this study was to investigate the effect of pioglitazone versus placebo on total daily insulin requirements and several pleiotropic factors in type 2 diabetes patients requiring hemodialysis.

Methods: The effect of pioglitazone (30 mg) versus placebo was explored in this prospective, randomized, double-blind parallel multicenter phase II study analyzing data from 36 patients with type 2 diabetes mellitus currently under hemodialysis (25 male, 11 female, aged 69.2 ± 7.9 years, baseline HbA1c 7.6 ± 0.9%). The most important efficacy parameters collected before dialysis and after an overnight fast at baseline and after 6 months were: total daily insulin dose, HbA1c, fasting blood glucose, adiponectin, HDL, LDL, triglycerides, NT-proBNP, and ultrafiltrate volume.

Results: Application of pioglitazone resulted in a significant decrease of the daily insulin dose by 35% versus baseline (placebo: -10%, n.s.), improvement in HbA1c (-0.60 ± 0.87%, p = 0.015; placebo: 0.21 ± 1.1%, n.s.) and adiponectin (7.33 ± 4.80 mg/l, p < 0.001; placebo: -1.37 ± 2.56 mg/l, n.s.). Slight improvements or no changes were seen with fasting glucose, triglycerides, HDL, LDL and NT-proBNP. There was no indication of increased hypoglycemia risk and volume overload by the addition of pioglitazone.

Conclusions: Addition of pioglitazone to insulin in patients with late-stage kidney failure requiring hemodialysis is a well-tolerated treatment option that improves glycemic control with simultaneous insulin-sparing potential.