Predictive value of early weight loss in obesity management with orlistat:: an evidence-based assessment of prescribing guidelines

OBJECTIVE: To assess the clinical usefulness of published guidelines for the use of orlistat, by studying whether weight loss greater than or equal to 2.5 kg during a 4 week dietary lead-in period, and weight losses of greater than or equal to 5% after 12 weeks and greater than or equal to 10% after 6 months of drug therapy predict weight loss and risk factor changes after 2 years. DESIGN: A retrospective analysis of pooled data from 2 multicentre, randomised, placebo-controlled clinical trials with similar design. SETTING: Twenty-nine centres throughout Europe. PARTICIPANTS: Two hundred and twenty men and women (BMI 28 - 43 kg /m(2)) who completed 2 years of treatment. INTERVENTION: After a 4 week hypocaloric diet plus placebo, 2 years of treatment with orlistat 120 mg tid, plus a hypocaloric diet for the first year and a weight maintenance diet in year two. MAIN OUTCOME MEASURES: Weight loss and obesity-related risk factor changes. RESULTS: Weight loss greater than or equal to 5% body weight after 12 weeks of diet plus orlistat therapy was a good indicator of 2 year weight loss, whereas weight loss of greater than or equal to 2.5 kg during the 4 week lead-in and greater than or equal to 10% after 6 months did not add significantly to the prediction of 2 year outcomes. Patients who lost greater than or equal to 5% of their weight at 12 weeks (n = 104, 47.3%) lost significantly more weight after 2 years than others: - 11.9% (95% confidence interval (CI) - 13.4% to - 10.3%) vs -4.7% (- 5.7% to - 3.7%) (P = 0.0001), and had significantly greater reductions in total cholesterol, LDL-cholesterol, triglycerides, glucose, insulin, and blood pressure. Among those who achieved greater than or equal to 5% weight loss at 12 weeks, the overall health benefits were not significantly greater in patients who went on to lose greater than or equal to 10% body weight at 6 months compared with those who did not achieve greater than or equal to 10% weight loss by month 6. CONCLUSIONS: Of the criteria currently suggested for assessing response to orlistat treatment, weight loss of greater than or equal to 5% at 12 weeks accurately predicts sustained improvements in weight and major risk factors at 2 years, while other suggested criteria are less useful.