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

Abstract

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.

Exploration and Development of PPAR Modulators in Health and Disease: An Update of Clinical Evidence

“…TZD-induced weight gain is attributable to increased subcutaneous fat depots due to body fat accumulation and redistribution, and body fluid retention [161]. Furthermore, in one clinical study, individuals given rosiglitazone had lower fasting plasma peptide YY and experienced increased hunger [162]. Such an inhibitory effect on peptide YY, which is an appetite suppressor, may also partly explain TZD-induced weight gain.…”

Safety and Tolerability of the Treatment of Youth-Onset Type 2 Diabetes

“…Peripheral edema and excessive weight gain are known adverse effects of rosiglitazone as well as other thiazolidinediones (14–18). However, peripheral edema occurred in only 1.7% of participants in the M + R group, which was not significantly more than in the other two groups and compares favorably to the 4–6% occurrence of edema in similar trials of adults (17,18). In addition, using the protocol-defined AE criteria set a priori (>10% increase in BMI between visits), excessive weight gain occurred in 9.0% of the M + R group compared with 4.3 and 7.3% in the M and M + L groups, respectively (not statistically significant).…”

“…The apparent contradiction between equivalent incidence of excessive weight gain between 3-month visits across treatment and significantly higher BMI across 60 months in the M + R group can be explained by the specificity of the study’s definition of excessive weight gain as an AE, which was designed primarily to provide an early signal of safety concerns. Studies of overweight adults treated with rosiglitazone have shown a gain in BMI ranging from 1.1 kg/m 2 after 12 weeks (17) to 0.35 after 24 weeks (15), which compares to about 0.4 at 12 weeks and 0.7 at 24 weeks among participants in TODAY’s M + R group (6). Weight gain from rosiglitazone seems to be a potential problem in children and adolescents, as it is in adults.…”