XENical in the prevention of diabetes in obese subjects (XENDOS) study

• the XENical in the prevention of diabetes in obese subjects (XENDOS) investigated the long-term (four years) diabetes-preventing and weight reducing effects of orlistat in combination with lifestyle changes in obese patients
  • a double-blind, randomised, placebo-controlled, prospective, four-year trial
    • subjects included in the trial were 30–60 years old (mean 43 years); all subjects had BMI > 30.0 kg/m2 (mean 37 kg/m2)
    • all subjects included in the trial were non-diabetic (determined by a baseline two-hour OGTT) - however a minority (21%) had impaired glucose tolerance.
    • exclusion criteria included diabetes, recent myocardial infarction, uncontrolled hypertension, symptomatic cholelithiasis, bariatric surgery, active gastrointestinal or pancreatic disorder, symptomatic psychiatric disorder or abuse
    • 3,305 obese patients (55% females, 21% with IGT) were included in the study. Patients were randomly assigned to 120 mg of orlistat three times day or placebo
      • also patients were prescribed an energy reduced diet of minus 800 kcal/day compared with the estimated total daily energy intake (with 30% of the energy from fat)
      • all the patients were also instructed to walk one km/day over and above their ordinary level of physical activity

Results and Conclusions:

• after four years:
  • completion of study:
    • orlistat-treated patients, 52% completed treatment compared with 34% of placebo recipients (P < 0.0001)
  • after 4 years' treatment, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk reduction of 37.3% (P = 0.0032)
  • cumulative diabetes incidence in IGT patients was 18.8% in the orlistat group and 28.8% in the placebo group (p=0.0024), representing a risk reduction of 45%
    • there was no significant difference in incidence of diabetes between treatment groups in patients with normal glucose tolerance at baseline
  • mean weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg with placebo; P < 0.001) and similar between orlistat recipients with impaired (5.7 kg) or normal glucose tolerance (NGT) (5.8 kg) at baseline
    • a second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group (3.6 vs. 1.4 kg; P < 0.001)
• the study authors concluded:
  • compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population.
  • difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT and or NGT

Reference:

1. Torgerson JS et al. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004 Jan;27(1):155-61.