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Pharmacologic treatment of obesity: Pitfalls and new promises

Abstract:

Obesity is a chronic, stigmatized and costly disease with increasing prevalence acquiring pandemic proportions. Therefore, obesity prevention and management should be accomplished by high skills professionals, as with other common chronic diseases. Obesity substantially increases the risk of suffering a number of conditions, including type 2 diabetes mellitus, hypertension, dyslipidemia, coronary heart disease, congestive heart failure, stroke, gallbladder disease, non-alcoholic steatohepatitis, osteoarthritis, sleep apnea, and endometrial, breast, prostate, and colon cancer. An increase in all-cause mortality is also associated with higher body weight, since adipose tissue is an active endocrine organ that produces free fatty acids and pro-inflammatory mediators directly related to insulin resistance, hyperlipidemia, inflammation, thrombosis and hypertension. The need for a "magic bullet" in anti-obesity drug treatment has been recognized. Several pharmacological approaches have been proposed to promote weight loss and/or minimize weight regain; however, the anti-obesity pharmacological market has remained almost unchanged for years. Nevertheless, the recent past has been characterized by three major events: 1) the withdrawal, because of serious side effects, of two drugs widely used in Europe and in the US (fenfluramine and dexfenfluramine); 2) the widely clinical use of sibutramine and orlistat and 3) the development of new drugs like the endocannabinoid system antagonist, selective thyroid receptor agonists and MC-3R, MC4-R agonists that promise a new horizon in the management of this insidious condition.