Mechanisms of action and clinical applications of anti-obesity drugs currently available in Korea

Kyoung-Kon Kim

doi:10.5124/jkma.2019.62.11.588

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Kim: Mechanisms of action and clinical applications of anti-obesity drugs currently available in Korea

Pharmacotherapeutics

Journal of the Korean Medical Association 2019; 62(11): 588-597.

Published online: 12 November 2019

DOI: https://doi.org/10.5124/jkma.2019.62.11.588

Mechanisms of action and clinical applications of anti-obesity drugs currently available in Korea

Kyoung-Kon Kim, MD

Department of Family Medicine, Gachon University College of Medicine, Incheon, Korea.

Corresponding author: Kyoung-Kon Kim. zaduplum@gilhospital.com

Received 30 October 2019 Accepted 8 November 2019

Korean Medical Association

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Over the last 5 years, the Korean Ministry of Food and Drug Safety has approved four anti-obesity drugs for long-term weight management. In this review, the mechanisms of action and clinical applications of lorcaserin, naltrexone/bupropion, liraglutide, and phentermine/topiramate have been clarified. Lorcaserin stimulates proopiomelanocortin/cocaine- and amphetamine-regulated transcript neurons in the arcuate nucleus. Naltrexone/bupropion reduces body weight by controlling the hedonic reward system of food intake. The hypophagic effect of liraglutide depends on the direct activation of the proopiomelanocortin/cocaine- and amphetamine-regulated transcript neurons and indirect suppression of neuropeptide Y/agouti-related peptide neurons through gammaaminobutyric acid-dependent signaling, with an additional thermogenic effect. Phentermine/topiramate induces weight loss by elevating the norepinephrine levels in the hypothalamus, reducing energy deposition in the adipose tissue and skeletal muscle, and elevating the corticotropin-releasing hormone in the hypothalamus. In patients with high cardiovascular risks or type 2 diabetes mellitus, lorcaserin and liraglutide are appropriate. In patients with mood disorders, naltrexone/bupropion could be considered as the first choice of therapy. Notably, lorcaserin and liraglutide are neutral in the aspect of sleep disorder. In case of obese individuals with obstructive sleep apnea, liraglutide or phentermine/topiramate would be selected as the treatment option. These four drugs should be used after considering the patients' co-morbidities of obesity.

Keywords: Anti-obesity agents, Pharmacology, Hypothalamus

Figures and Tables

Table 1

Currently available anti-obesity drugs for long-term weight managementt

CV, cardiovascular; AE, adverse event; POMC, proopiomelanocortin; CART, cocaine- and amphetamine-regulated transcript; MOP-R, mu-opioid receptor; NA, not available; GLP-1, glucagon-like peptide 1; NPY, neuropeptide Y; AgRP, agouti-related peptide; GABA, γ-aminobutyric acid; CRH, corticotropin-releasing hormone.

Notes

^{Conflict of Interest} Kyoung-Kon Kim received an honorarium from Alvogen, Kwangdong, Ildong, and Novo Nordisk, and research funding from Ildong. The author have no other conflicts of interest to declare.

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ORCID iDs: Kyoung-Kon Kim
https://orcid.org/0000-0003-0374-2571
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