By Professor Juan Tamargo, Madrid, Spain
In recent years, the only pharmacologic treatment available for obesity has been orlistat, but the drug produces a modest weight loss and is poorly tolerated due to gastrointestinal side effects.
The Endocrinologic and Metabolic Drugs Advisory Committee of the Food and Drug Administration (FDA) approved the serotonin (5-HT) 2C receptor agonist lorcaserin (Belviq) for chronic weight loss management as an adjunct to diet and exercise in adult obese patients [body-mass index (BMI) >30 kg/m2] and overweight patients (BMI ≥ 27 kg/m2) with 1 or more weight-related comorbidities such as hypertension, dyslipidemia, sleep apnea, glucose intolerance or type 2 diabetes. The decision by the FDA opens the door to other pharmacological agents that also reduce body weight in overweight and obese patients.
Lorcaserin produces weight loss by suppression of appetite, which in turn reduces total energy intake. However, at therapeutic doses lorcaserin does not activate the 5-HT2B receptors expressed on cardiac valvular interstitial cells and pulmonary artery smooth muscle cells. Therefore is is unlikely that lorcaserin maight cause valvulopathy and pulmonary arterial hypertension previously described with nonselective serotonergic agents (i.e. fenfluramine) used for obesity management.
Lorcaserin also improves glycemic control (A1c decreased by 0.9%) in patients with type 2 diabetes, and it has modestly beneficial effects on lipids and does not have an adverse effect on blood pressure or heart ratel.
Lorcaserin is well tolerated, the most common side effects being headache, back pain, nasopharyngitis, and nausea.
Lorcaserinin was rejected in October 2010 by the FDA because of concerns about a cancer signal detected in preclinical animal studies. The FDA asked for more data, including results from the BLOOM-DM trial, a clinical study testing the weight-loss drug in overweight and obese subjects with diabetes. Furthermore, the advisory panel considered the weight loss in nondiabetic overweight and obese subjects “marginal” as the average weight loss in phase 3 clinical trials (BLOOM and BLOSSOM) averaged 5 to 6 kg. However, at the present time the FDA agreed that the risk of tumors in treated patients was “negligible”, but still expressed some concern about a possible increased risk of valvulopathy and adverse cardiovascular events associated with lorcaserin. Indeed, the combination of fenfluramine/ phentermine, was withdrawn from the market in the late 1990s, given the risks of heart-valve damage. Morevover, the safety of the combination of lorcaserin with other serotonergic or antidopaminergic agents (appeareance of serotonin syndrome or neuroleptic malignant syndrome) or with insulin in diabetic patients is unknown. Lorcaserin may cause disturbances in attention or memory, so that caution when driving or using hazardous machinery is recommended for patients starting treatment. At high doses, lorcaserin produces psychiatric disorders, including euphoria, dissociation, depression or suicidal ideas, and priapism. Lorcaserin is contraindicated in pregnancy (Pregnancy Category X) and in breast-feeding mothers. It is not recommended in pediatric populations.
1. Fidler MC, Sanchez M, Raether B, et al. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab. 2011;96:3067-3077. Abstract
2. O’Neil PM, Smith SR, Weissman NJ, et al. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study.Obesity. 2012. doi: 10.1038/oby.2012.66.
3. Food and Drug Administration. FDA approves Belviq to treat some overweight or obese adults [press release]. June 27, 2012.