Understanding the Mechanism of Action and Clinical Implications of Anti-Obesity Drugs Recently Approved in Korea

Abstract

The Korean Ministry of Food and Drug Safety has approved three anti-obesity drugs for long-term management in the past decade. In addition, since 2019, bariatric surgery has been financially supported by National Health Insurance Service in Korea. In this review, the mechanisms of action and the clinical implications of the recently approved anti-obesity drugs, lorcaserin, naltrexone/bupropion, and liraglutide are explained. Lorcaserin stimulates proopiomelanocortin (POMC)/cocaine- and amphetamine-regulated transcript (CART) neurons and inhibits neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons, which results in the activation of melanocortin 3/4 receptors. Naltrexone/bupropion stimulates POMC neurons through bupropion; this stimulation is augmented by blocking the autoinhibitory mechanism of POMC with naltrexone. The hypophagic effect of liraglutide is mediated through the direct activation of POMC/CART neurons and the indirect suppression of NPY/AgRP neurons through gamma-aminobutyric acid-dependent signaling, with adjunctive suppression of the mesolimbic dopamine reward system. In addition to liraglutide, another glucagon-like peptide-1 receptor agonist, semaglutide, is expected to be added to the list of anti-obesity drugs in the near future. In patients with obesity and high cardiovascular risk, lorcaserin was considered neutral and liraglutide was considered favorable, whereas inconclusive results were obtained for naltrexone/bupropion.