Lorcaserin, A 5-HT2C Receptor Agonist, Reduces Body Weight by Decreasing Energy Intake without Influencing Energy Expenditure

Context: Lorcaserin, a selective 5-hydroxytryptamine (5-HT)(2C) receptor agonist, reduces body weight. It is unclear whether weight loss is due to reduced energy intake (EI) or also to enhanced energy expenditure (EE). Objective: This study tested the effect of lorcaserin on EI and EE. Design, Participants, and Intervention: In a double-blind, randomized, placebo-controlled trial, 57 (39 women) overweight and obese (body mass index, 27-45 kg/m(2)) adults were randomized to placebo (n = 28) or 10 mg twice daily lorcaserin (n = 29) for 56 d. Weight maintenance was imposed during d 1-7. Beginning on d 8, participants followed a diet and exercise plan targeting a 600 kcal/d deficit. Outcomes: At baseline and after 7 and 56 d of treatment, we measured body weight, body composition (dual x-ray absorptiometry), blood pressure, heart rate, EI at lunch and dinner, subjective appetite ratings, and 24-h EE and 24-h-respiratory quotient (RQ), measured by indirect calorimetry in a respiratory chamber. Results: After 7 d of weight maintenance, EI was significantly (P < 0.01) reduced with lorcaserin but not placebo (mean +/- SEM for lorcaserin, -286 +/- 86 kcal; placebo, -147 +/- 89 kcal). After 56 d, lorcaserin resulted in significantly larger reductions in body weight (lorcaserin, -3.8 +/- 0.4 kg; placebo, -2.2 +/- 0.5 kg; P < 0.01), EI (lorcaserin, -470 +/- 87 kcal; placebo, -205 +/- 91 kcal; P < .05), and appetite ratings than in placebo. Changes in 24-h EE and 24-h RQ did not differ between groups, even after 24-h EE was adjusted for body weight and composition. Compared with placebo, lorcaserin had no effect on systolic or diastolic blood pressure or heart rate after 56 d. Conclusions: Lorcaserin reduces body weight through reduced EI, not altered EE or RQ. (J Clin Endocrinol Metab 96: 837-845, 2011)