The cardiovascular safety of antiobesity drugs—analysis of signals in the FDA Adverse Event Report System Database

• Published in: International Journal of Obesity 2020-05, Vol.44 (5), p.1021-1027
• Main Authors: Gorelik, Einat, Gorelik, Boris, Masarwa, Reem, Perlman, Amichai, Hirsh-Raccah, Bruria, Matok, Ilan
• Format: Article
• Language: English
• Subjects: 692/499; 692/700/2817; Adverse events; Arrhythmia; Bupropion; Cardiotoxicity; Cerebral infarction; Disorders; Drug approval; Drug therapy; Drugs; Epidemiology; FDA approval; Health Promotion and Disease Prevention; Health risk assessment; Heart attack; Hypertension; Internal Medicine; Lorcaserin; Marketing; Marketing research; Medicine; Medicine & Public Health; Metabolic Diseases; Myocardial infarction; Naltrexone; Public Health; Pulmonary hypertension; Regulatory agencies; Safety; Sibutramine; Topiramate; Type 2 diabetes
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/s41366-020-0544-4

Aims Over the past several decades, many antiobesity drugs have been withdrawn from the market due to unanticipated adverse events, often involving cardiotoxicity. This study aimed to evaluate the presence of cardiovascular safety signals with currently marketed antiobesity drugs. Methods We used the US Food and Drug Administration Adverse Event Reporting System (FAERS) database and retrieved data from January 2013 through December 2018. We performed disproportionality analyses to detect cardiovascular safety signals with three antiobesity drugs recently approved for marketing: lorcaserin, naltrexone–bupropion, phentermine, and phentermine–topiramate. Three main cardiovascular outcomes were evaluated: valvular disorders, and pulmonary hypertension (PH) and other cardiovascular events (myocardial infarction, stroke, cardiovascular death, cardiac failure, and arrhythmia). Results During the evaluated period, a total of 6,787,840 adverse event reports were submitted to FAERS. Of these, 2687 involved lorcaserin, 3960 involved phentermine/phentermine–topiramate, and 2873 involved naltrexone–bupropion. Lorcaserin was associated with a significantly greater proportion of reports of valvular disorders (ROR = 4.39; 95% CI 2.72–5.07). None of the antiobesity drugs were associated with a safety signal for valvulopathy, PH, or other cardiovascular events. Conclusions Our analyses revealed a signal for valvular disorders with lorcaserin and did not detect a safety signal for other cardiovascular events with recently approved antiobesity drugs. Further research is needed to explore and validate this signal.