AIMS:Unfortunately, growing number of type 2 diabetic hemodialysis (HD) patients with insulin resistance are now being diagnosed in Japan. Worse still, PPARgammaagonists such as pioglitazone are now contraindicated in diabetic HD patients in Japan. In this study we evaluated the efficacy of pioglitazone in diabetics on HD. METHODS:Following a 12-week baseline period, we enrolled a study population of poorly controlled diabetic HD patients who had mean hemoglobin A1c (HbA1c) levels greater than 6.5% at baseline and who were not receiving insulin injection therapy. The patients were administered pioglitazone 15mg daily with their morning meal for the first 4 weeks. Subsequently, the doses were titrated by dose-doubling to a maximum of 30mg/day if no adverse effects appeared. The efficacy was determined by monitoring glycemic control (plasma glucose and HbA1c), and insulin resistance (plasma immunoreactive insulin (IRI) and homeostasis model assessment for insulin resistance (HOMA-R)). Safety and tolerance were determined by monitoring clinical and laboratory parameters. RESULTS:Pioglitazone was effective in reducing plasma glucose and HbA1c from the baseline levels from week 4 after the commencement of treatment. The agent was also effective in reducing triglycerides. Plasma IRI and HOMA-R, two parameters of insulin resistance, decreased significantly at 4 weeks, and the decreases continued for 24 weeks. Systolic and diastolic blood pressures were statistically lower at 8 weeks. No serious adverse effects such as hypoglycemia, liver impairment, or rhabdomyolysis were observed in any of the patients. CONCLUSIONS:Pioglitazone was effective in the treatment of diabetics on dialysis therapy. Pioglitazone might have the potential to reduce the number of type 2 diabetics on HD who ultimately require insulin injection therapy.