Obesity is a major correlate of cardiovascular disease. Weight loss improves 
cardiovascular risk factors and has the potential to improve outcomes. Two 
drugs, phentermine plus topiramate and lorcaserin, have recently been approved 
by the US Food and Drug Administration for the indication of obesity; a third, 
bupropion plus naltrexone, is under consideration for approval. In clinical 
trials, these drugs cause weight loss and improve glucose tolerance, lipid 
profile, and, with the exception of bupropion plus naltrexone, blood pressure. 
However, their effect on cardiovascular outcomes is unknown. In defining 
appropriate roles for these drugs in preventive cardiology, it is important to 
remember the checkered history of drugs for obesity. New weight-loss drugs share 
the serotonergic and sympathomimetic mechanisms that proved harmful in the cases 
of Fen-Phen and sibutramine, respectively, albeit with significant differences. 
Given these risks, randomized cardiovascular outcomes trials are needed to 
establish the safety, and potential benefit, of these drugs. This review will 
discuss the history of pharmacotherapy for obesity, existing efficacy and safety 
data for the novel weight-loss drugs, and issues in the design of postapproval 
clinical trials.