Lorcaserin: balancing efficacy with potential risks

• Published in: The Lancet (British edition) Vol. 392; no. 10161; pp. 2239 - 2240
• Main Authors: Unamuno, Xabier, Frühbeck, Gema
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 24.11.2018; Elsevier Limited
• Subjects: Arteriosclerosis; Atherosclerosis; Benzazepines; Body weight; Body weight loss; Camellia; Cardiovascular disease; Cardiovascular diseases; Data processing; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; Disease control; Glucose; Health care; Health risks; Heterogeneity; Humans; Insulin; Melanocortin; Melanocortin MC4 receptors; Metabolism; Obesity; Overweight; Patients; Physicians; Precision medicine; Primary care; Psychological aspects; Receptors; Remission; Risk analysis; Risk factors; Weight control; Weight loss; United States > US; Europe
• ISSN: 0140-6736; 1474-547X; 1474-547X
• DOI: 10.1016/S0140-6736(18)32460-7

Investigators randomly assigned 12 000 overweight or obese (body-mass index ≥27 kg/m2) patients—of whom 7702 (64·2%) were men and 4298 (35·8%) were women, of median age 64 years (IQR 58–69) and body-mass index 35 kg/m2 (32–39)—with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to treatment with lorcaserin or placebo. Miguel Riopa/Contributor/Getty Images In the contemporary era of precision medicine, the application of such strategies in obesity management has not progressed.6 For some physicians, the overall magnitude of the effects of lorcaserin might seem moderate; the resulting weight loss might be disappointing, especially if it does not lower the risk of cardiovascular disease, and evidence exists that effective weight management delivered in the primary care setting can produce sustained remission in type 2 diabetes.7 Physicians might be uncomfortable prescribing lorcaserin on a general basis and might instead prefer to prescribe it on a temporary basis (ie, for 6–12 months); patients who respond well and for whom treatment should be continued could be identified within the first few months of treatment. Preclinical data suggest the possibility of glucose-lowering effects independently of weight loss via melanocortin-4 receptors on cholinergic preganglionic neurons.11 Clamp studies show that lorcaserin ameliorates insulin sensitivity, reduces hepatic glucose production, and increases glucose disposal.11 A conceptual heterogeneity across diverse weight-loss studies hinders comparison among different anti-obesity drugs.