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.
