Multicenter, placebo-controlled trial of lorcaserin for weight management.
BACKGROUND
Lorcaserin is a selective serotonin 2C receptor agonist that could be useful in reducing body weight.


METHODS
In this double-blind clinical trial, we randomly assigned 3182 obese or overweight adults (mean body-mass index [the weight in kilograms divided by the square of the height in meters] of 36.2) to receive lorcaserin at a dose of 10 mg, or placebo, twice daily for 52 weeks. All patients also underwent diet and exercise counseling. At week 52, patients in the placebo group continued to receive placebo but patients in the lorcaserin group were randomly reassigned to receive either placebo or lorcaserin. Primary outcomes were weight loss at 1 year and maintenance of weight loss at 2 years. Serial echocardiography was used to identify patients in whom valvulopathy (as defined by the Food and Drug Administration) developed.


RESULTS
At 1 year, 55.4% of patients (883 of 1595) receiving lorcaserin and 45.1% of patients (716 of 1587) receiving placebo remained in the trial; 1553 patients continued into year 2. At 1 year, 47.5% of patients in the lorcaserin group and 20.3% in the placebo group had lost 5% or more of their body weight (P<0.001), corresponding to an average loss of 5.8+/-0.2 kg with lorcaserin and 2.2+/-0.1 kg with placebo during year 1 (P<0.001). Among the patients who received lorcaserin during year 1 and who had lost 5% or more of their baseline weight at 1 year, the loss was maintained in more patients who continued to receive lorcaserin during year 2 (67.9%) than in patients who received placebo during year 2 (50.3%, P<0.001). Among 2472 patients evaluated at 1 year and 1127 evaluated at 2 years, the rate of cardiac valvulopathy was not increased with the use of lorcaserin. Among the most frequent adverse events reported with lorcaserin were headache, dizziness, and nausea. The rates of serious adverse events in the two groups were similar.


CONCLUSIONS
In conjunction with behavioral modification, lorcaserin was associated with significant weight loss and improved maintenance of weight loss, as compared with placebo. (Funded by Arena Pharmaceuticals; ClinicalTrials.gov number, NCT00395135.)
Smith
Steven R
SR
Translational Research Institute for Metabolism and Diabetes, Florida Hospital and the Sanford-Burnham Institute, Winter Park, FL 32789, USA. steven.r.smith.MD@flhosp.org
Weissman
Neil J
NJ
Anderson
Christen M
CM
Sanchez
Matilde
M
Chuang
Emil
E
Stubbe
Scott
S
Bays
Harold
H
Shanahan
William R
WR
D000328:Adult; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001521:Behavior Therapy; D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure; D002318:Cardiovascular Diseases; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D006349:Heart Valve Diseases / Q000453:epidemiology; D006801:Humans; D007328:Insulin / Q000097:blood; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000628:therapy; D050177:Overweight / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D012307:Risk Factors; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D055105:Waist Circumference; D015431:Weight Loss / Q000187:drug effects
D019440:Anti-Obesity Agents; D001552:Benzazepines; D007328:Insulin; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists; C506658:lorcaserin