Rosiglitazone decreases fasting plasma peptide YY3–36 in type 2 diabetic women: a possible role in weight gain?

Rosiglitazone often results in weight gain. We hypothesized that rosiglitazone may modulate circulating levels of ghrelin and peptide YY 3–36 and this modulation may be related to weight-gaining effect of this agent. This study was designed as an open-label, randomized, controlled trial of 3-month duration. Women with newly diagnosed type 2 diabetes were studied. Twenty-eight of the 55 eligible participants were randomly assigned to receive rosiglitazone (4 mg/d). Twenty-seven patients with diabetes matched for age and body mass index served as controls on diet alone. We evaluated the effects of 3 months of rosiglitazone treatment on fasting peptide YY 3–36 and ghrelin levels, and anthropometric measurements. The 3-month administration of rosiglitazone reduced fasting plasma peptide YY 3–36 levels by 25%, the between-group difference was statistically significant. No effect of this thiazolidinedione compound on fasting ghrelin concentrations was observed at the end of study. The ghrelin/body mass index ratio also did not change significantly after treatment. Seventy-five percent of the women with diabetes complained of increased hunger at the end of study. Nevertheless, all subjects exhibited a decrease in fasting PYY levels after 3 months of rosiglitazone therapy, irrespective of the levels of hunger. There was no significant correlation between changes in peptide YY 3–36 and those in anthropometric parameters and insulin sensitivity at the end of the study. Rosiglitazone-induced decrease in fasting peptide YY 3–36 levels may in part contribute to orexigenic and weight-gaining effect of this thiazolidinedione derivative.