Analysis of the XENDOS study (Xenical in the Prevention of Diabetes in Obese Subjects).

OBJECTIVE: To present an overview and analysis of the previously published XENDOS (Xenical in the Prevention of Diabetes in Obese Subjects) study.

METHODS: The design, methods, and results of the XENDOS study are reviewed. On the basis of the findings, conclusions are discussed.

RESULTS: The XENDOS study was a double-blind, prospective investigation with 3,305 participants, who had either normal or impaired glucose tolerance. The patients were randomly assigned to lifestyle plus placebo intervention or lifestyle changes plus orlistat (Xenical) (120 mg 3 times daily). After 4 years of treatment, the cumulative incidence of type 2 diabetes was 9.0% in the placebo group and 6.2% in the orlistat group (P = 0.0032). The incidence of diabetes was low and not significantly different in the two treatment arms of the study in those patients with normal glucose tolerance at baseline. In patients with impaired glucose tolerance, however, the conversion to type 2 diabetes was significantly greater in the placebo group than in the orlistat-treated group (P = 0.0024). Division of the baseline fasting plasma glucose levels into an upper and a lower subclassification revealed a significant difference (P < 0.05) in incidence of diabetes between the placebo (17.8%) and orlistat (9.4%) groups in the upper stratification but no significant difference in the lower subclassification (3.2% versus 2.5%, respectively). The weight loss was significantly greater in the orlistat group than in the placebo group for the entire study period (P < 0.001).

CONCLUSION: In the XENDOS study, orlistat therapy reduced the incidence of diabetes beyond the result achieved with lifestyle changes only, an effect that was especially evident in patients with baseline impairment of glucose tolerance.