Current Pharmacological Approaches in Obesity Treatment

The recognition of obesity as a chronic disease and its relentless expansion throughout the world in the last few decades has driven the need for more efficient treatments. Pharmacological approaches have been attempted since the twentieth century, but most of the drugs failed to demonstrate an adequate balance between weight loss and side effects. In the last few years, new, less stringent criteria from the Food and Drug Administration allowed the introduction of new compounds or combinations of old ones. The single new compounds are lorcaserin, an agonist of central 5HT2C receptors and liraglutide, an agonist of glucagon-like peptide 1 receptors. New, fixed-dose combination drugs are naltrexone-bupropion (an opioid antagonist and an antidepressant, respectively) and phentermine-topiramate (a central noradrenaline release stimulant and an antiepileptic, respectively). Orlistat, an inhibitor of gastrointestinal lipases, has also been available for some years. Weight loss effect after one year found in double blind, placebo controlled clinical trials ranges from circa 3 kg for orlistat and lorcaserin to 9 kg for the phentermine-topiramate combination. Drugs with higher weight reductions generally present a higher probability of adverse effects. The relatively modest effect of all the drugs approved for obesity treatment clearly shows that pharmacotherapy cannot be the sole solution for the overwhelming obesity epidemic. Nevertheless, a more personalized use of the existing compounds and the possibility of new drugs based on different mechanisms may certainly help to circumvent the powerful energy-conserving mechanisms that make sustained weight loss extremely difficult to achieve.

Keywords: Appetite, Bupropion, Cardiovascular effects, Clinical trials, Diabetes mellitus, Drug combination, Efficacy, Liraglutide, Lorcaserin, Monotherapy, Naltrexone, Obesity, Orlistat, Overweight, Pharmacotherapy, Phentermine, Safety, Side-effects, Topiramate, Weight loss.