New medications for treatment of obesity: metabolic and cardiovascular effects

The management of obesity remains a major challenge. Dietary therapy often fails, whereas bariatric surgery, although successful, is demanding and applicable to a limited number of patients. Drug therapy has had many setbacks over the past 20 years because of serious adverse effects; however, several new drugs for the treatment of obesity are either licensed in some parts of the world, submitted for registration, or completing phase III trials. These include combinations (at low dose) of existing drugs, e.g., bupropion + naltrexone (Contrave), phentermine + topiramate (Qsymia), higher doses of existing drugs licensed for other indications (liraglutide, 3 mg), and new entities (lorcaserin). We discuss the challenges and opportunities for obesity pharmacotherapy and review in detail the efficacy of the new drugs regarding weight loss and both desirable and potential undesirable cardiovascular (CV) and metabolic risk factors. Substantial barriers remain, even if the drugs are approved, in successfully integrating these agents into weight management practice, largely related to cost, patient acceptability, and clinician willingness to be engaged in obesity treatment. Although hard clinical outcome benefit (at least for CV outcomes) has yet to be established, obesity pharmacotherapy may soon address many of the challenges in the clinical management of obesity, although newer and better drug combinations and more evidence of benefit from appropriately designed outcome trials is needed.