Smith, Steven R2; O'Neil, Patrick M3; Astrup, Arne8; Finer, Nicholas5; Sanchez-Kam, Matilde6; Fraher, Kyle6; Fain, Randi7; Shanahan, William R6
1 Obesity Research, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet2 Translational Research Institute for Metabolism and Diabetes, Florida Hospital and the Sanford-Burnham Medical Research Institute, Orlando, Florida, USA.3 Weight Management Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina4 Department of Nutrition, Exercise and Sports, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet5 National Centre for Cardiovascular Prevention and Outcomes, UCL Institute of Cardiovascular Science, University College London, London6 Arena Pharmaceuticals Inc, San Diego, California7 Eisai Inc, Woodcliff Lake, New Jersey8 Department of Nutrition, Exercise and Sports, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet
OBJECTIVE: To identify an early treatment milestone that optimizes sensitivity and specificity for predicting ≥5% weight loss at Week (W) 52 in patients with and without type 2 diabetes on lorcaserin or placebo. METHODS: Post hoc area under the curve for receiver operating characteristic analyses of data from three phase 3 trials comparing lifestyle modification+placebo with lifestyle modification+lorcaserin. A total of 6897 patients (18-65 years; BMI, 30-45 or 27-29.9 kg/m(2) with ≥1 comorbidity) were randomized to placebo or lorcaserin 10 mg bid. Changes (baseline to W52) in cardiometabolic parameters were assessed. RESULTS: Response (≥5% weight loss from baseline) at W12 was a strong predictor of W52 response. Lorcaserin patients with a W12 response achieved mean W52 weight losses of 10.6 kg (without diabetes) and 9.3 kg (with diabetes). Proportions achieving ≥5% and ≥10% weight loss at W52 were 85.5% and 49.8% (without diabetes), and 70.5% and 35.9% (with diabetes). Lorcaserin patients who did not achieve a W12 response lost 3.2 kg (without diabetes) and 2.8 kg (with diabetes) at W52. Responders had greater improvements in cardiometabolic risk factors than the modified intent-to-treat (MITT) population, consistent with greater weight loss. CONCLUSIONS: ≥5% weight loss by W12 predicts robust response to lorcaserin at 1 year.