Current and Emerging Pharmacotherapies for Obesity

Abstract

Obesity is prevalent chronic condition associated with increased morbidity and mortality. Pharmacotherapy is indicated as adjuncts to health behavior modification when overweight or obese adults fail to achieve or maintain the desired weight loss to improve their health status. Orlistat, a lipase inhibitor that decreases fat absorption by 30%, is the only anti-obesity agent approved for long-term therapy in Canada. With the rapid advance in knowledge of the pathogenesis of obesity, the list of potential anti-obesity agents has increased considerably. Anti-obesity drugs lower body weight by 5-15% and fall into 3 major groups: centrally acting medications that inhibit appetite or promote satiety, or both; drugs that act peripherally to impair nutrient absorption; and drugs that increase energy expenditure. Phentermine and diethylpropion are adrenergic stimulants that inhibit appetite by increasing the release and reuptake of norepinephrine and dopamine in the brain. A low-dose combination of phentermine and extended-release topiramate, an antiepileptic drug, has recently been approved in the US. Lorcaserin decreases food consumption and promotes satiety by selectively activating 5-HT2C receptors on anorexigenic pro-opiomelanocortin (POMC) neurons located in the hypothalamus. Another FDA-approved combination pill - bupropion and naltrexone, increases dopamine activity in the brain, and increases in energy expenditure by increasing activity of POMC neurons. It regulates the dopamine reward system and control food cravings and overeating. The most recent FDA-approved drug is liraglutide, an incretin analogue that inhibits appetite and energy intake. The benefits and risks of current and emerging anti-obesity agent will be discussed in the presentation.