비만 치료의 최신 지견
New Drugs for Obesity Treatment
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참고문헌
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초록
지금까지 수천 년간 인간의 진화과정에서, 농작물 수확과 공급의 획기적 발전은 상상할 수도 없었던 과도한 양의 에너지를 인체생리에 가져다 주었다. 아직, 이런 과도한 영양 상태를 해결하기보다는, 기아 극복에 맞추어진 인체생리는 초과에너지를 지방에 저장하여 발생하는 비만 상태에 취약하게 되었다[1]. 하지만 비만의 궁극적 치료인 식욕감소-유발 약제 개발은, 수천 년의 인간진화를 단 수십 년에 바꾸려는 어려운 과정이었다. 이런 어려운 약제의 개발 과정에서 많은 시행착오를 겪어 왔다.
Abstract
There have recently been many advances in obesity treatment, including lifestyle modifications and pharmacological and surgical treatments. Specifically, pharmacological strategies have improved significantly. However, the history of the development of medications aimed at weight loss is complicated. The Federal Drug Administration (FDA) withdrew anti-obesity drugs such as fenfluramine, dexfenfluramine, and phenylpropylamine due to their unwanted side effects. Moreover, sibutramine was voluntarily withdrawn from the market and a new drug, rimonabant, has been suspended in the middle of a clinical trial due to unacceptable side effects. The FDA has approved four new anti-obesity drugs in recent years. Lorcaserin is a selective 5-hydroxytryptamine receptor 2c (5-HT2c) agonist. The pharmacological mechanism of action of this drug is similar to fenfluramine and dexfenfluramine, but lorcaserin is specific for 5-HT2c, which are located almost exclusively in the central nervous system and are not found in heart valves. Three phase 3 clinical trials for lorcaserin have been published recently; weight reduction was successful and no side effects involving the heart were found. Furthermore, the FDA has also approved phentermine/topiramate controlled-release (PHEN/TPM CR), which is composed of a combination of immediate-release phentermine and controlled-release topiramate. Weight reduction achieved with PHEN/TPM CR was demonstrated to be better than all other anti-obesity drugs. Lastly, the combination therapy bupropion/naltrexone activates proopiomelanocortin neurons and inhibits opioid-mediated negative feedback by synergism. Similar to liraglutide, a long-acting analogue of the hormone glucagon-like peptide-1, this treatment showed significant weight loss and metabolic improvements. However, in addition to its efficacy, clinicians should consider its side effects before use.
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