추계 Single Topic Symposium-편집.hwp

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Anti-obesity medication 서연석고려대학교의과대학소화기내과 Yeon Seok Seo Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea 서론 비만은에너지의불균형상태, 즉에너지섭취가에너지소비를초과하는상태로서, 이에대한치료로 는식이조절,

1 Anti-obesity medication 서연석고려대학교의과대학소화기내과 Yeon Seok Seo Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea 서론 비만은에너지의불균형상태, 즉에너지섭취가에너지소비를초과하는상태로서, 이에대한치료로 는식이조절, 운동및생활습관의개선을통해에너지섭취를줄이고에너지소비를증가시킴으로써체 중감량을유도하는것이권장된다. 비만환자에서처음체중으로부터 5-10% 의체중감량은심혈관질환 의위험을줄이고제 2 형당뇨병의발생을예방하거나지연시키는것으로알려져있다. 1-3 그러나여러가 지요인으로인해이와같은방법이성공하는경우는그리많지않으며, 특히비만한사람의경우식욕 을조절하는기전이더약한경우가많고, 체중감소자체가체중조절에대한신념을약화시키는심리적 변화를유발하기도하며, 비만환자에서는위장관의음식물섭취에의한되먹이기전 (feedback mechanism) 이약화되어음식물섭취에도포만감을잘느끼지못하므로더욱체중조절이힘들게된다. 4,5 따라 서약물의도움으로체중감량을하려는시도들이이미오래전부터계속되어오고있다. 이글에서는 다양한비만치료제들의작용기전과효과및부작용들에대해살펴보고자한다. 본론 1. 체내에너지섭취및에너지소비에대한조절 우리몸에서는다양한인자들이순환하면서뇌와정보를공유하여에너지섭취및소비의균형을맞추 고체중을일정범위이내로유지한다. 6,7 음식을섭취하면소장과대장에서 peptide YY, cholecystokinin, glucagon-like peptide-1 (GLP-1) 등을분비하여포만감을느끼게하며, 반대로음식을섭취한후시간이 지나면서위에서 ghrelin 을분비하여식욕을유발하게한다. 이와같은인자들은음식섭취에즉각적으 27

2 2016 대한간학회추계 Single Topic Symposium 로반응하여공복감이나포만감을유발하게하는반면, leptin이나 insulin은개인의전반적인대사상태를대변하는체내의지방양에의해분비가조절되어음식섭취에영향을주게된다. 6,8 이러한신호들을종합하여음식섭취를유발또는억제하는작용을하는체내시스템으로는 melanocortin system이가장잘알려져있다. Melanocortin system은 melanocortin receptor (MCR), pro-opiomelanocortin (POMC)-derived MCR agonists 및 MCR competitive antagonist/inverse agonist인 agouti and agouti-related protein (AgRP) 을발현하는세포들로구성된다. 9,10 AgRP 및 POMC를발현하는뉴런들은각각 neuropeptide Y (NPY) 및 cocain-and-amphetamine-regulated transcript (CART) 를함께발현하며, 시상하부 (hypothalamus) 의 arcuate nucleus (ARC) 내에서많이관찰되나, POMC 뉴런은 caudal brainstem의 nucleus of the solitary tract (NTS) 도존재한다. 6 시상하부내의 POMC 및 AgRP 뉴런들은 hypothalamic paraventricular nucleus (PVH), dorsomedial nucleus, ventromedial nucleus 및 lateral hypothalamic area (LHA) 등에직접적으로연결되어에너지항상성 (homeostasis) 조절에관여하게된다. 11 즉, POMC 뉴런이활성화되면 α -melanocyte stimulating hormone (α-msh) 이분비되어 MC4R을통해식욕을억제하게된다. POMC 뉴런이자극될때 α-msh만분비되는것이아니라 β-endorphin도함께분비하는데분비된 β-endorphin은 POMC 뉴런을억제하는자가억제되먹이기전 (autoregulatory feedback mechanism) 으로작용하게된다. 반면 AgRP 뉴런이활성화되면 MC4R을통해식욕을증가시키도록하며또한 POMC 뉴런을억제하여이효과를더욱증강시킨다. 이러한 melanocortin system의대표적인조절인자는 leptin으로서 POMC 및 AgRP 발현뉴런모두 leptin에대한수용체를발현하는데, leptin은 POMC 발현뉴런을활성화시키고 NPY/AgRP 발현뉴런은억제함으로써식욕을감소시키게된다 비만치료제비만의약물치료에여러비만치료지침들은다음과같은사항들을권고하고있다 13 : 첫째, 비만치료제를처방하더라도생활습관의개선은병행되어야하며비만치료제는식이조절과운동등체중감량을위한생활습관교정을하는환자의의지를더강화시키는작용을할뿐임을강조해야한다. 둘째, 의사와환자모두사용하는약제의효과및부작용에대해잘알고있어야한다. 셋째, 약물치료 3-4개월후까지도임상적으로의미있는체중감량이없다면다른치료로전환하여야한다. 현재미국이나유럽에서비만치료제로의사용이허가된약물로는 phentermine, orlistat, lorcaserin, phentermine/topiramate ER, naltrexone SR/bupropion SR 및 liraglutide가있다. 이약제들중현시점에서국내에서사용이가능한약제는 orlistat와 lorcaserin이며다른대부분의약제들도국내출시를준비하고있다. 1) 기초대사율증가를통해에너지소비를증가시켜체중감량을유도하는약물 갑상선호르몬이기초대사율 (basal metabolic rate) 을늘려에너지소비를증가시킴으로써체중을감량 28 대한간학회 The Korean Association for study of the Liver

3 서연석 Anti-obesity medication 시키는대표적인약제로서 14 19세기에비만치료제로널리사용되었다. 그러나체중감량이지방의감소보다는근육의감소에의한다는단점과안절부절못함, 수면장애, 심부전발생증가등갑상선기능항진에따른부작용으로현재는사용되지않는다. 15 2) 섭취된지방의흡수를억제하여체중감량을유도하는약물 Orlistat (Xenical ) Orlistat는위장관지질분해효소억제제로서췌장과위의지질분해효소를억제하여섭취된지방의흡수를감소시키는작용을한다. 16 Orlistat는체중을감소시키고총콜레스테롤및 LDL 콜레스테롤, 식전혈당및혈압의감소등심혈관위험인자를호전시킨다. 17 총 16개의연구에대한메타분석에서는 1년간치료시위약군에비해 2.9 kg의추가적인체중감량을보였으며, 18 당뇨병전기 (prediabetes) 환자에서당뇨병발생을감소시키는효과를입증하였다. 19 섭취된약물은대부분대사되지않고대변으로배설되기때문에전신적인약리작용은거의없는, 비만치료제중가장안전한약제의하나로알려져있으며 20 청소년기환자들에대한사용도가능하다. 21 가장흔한부작용은설사, 변실금, 지방변, 가스팽만, 소화장애등위장관계부작용이며, 22,23 이러한부작용으로인해이약제의사용을꺼리게되는경우가적지않다. 반면에식사당지방섭취를 15 g 이내로제한하면이와같은부작용의발생을막거나줄일수있기때문에환자들에게저지방식이를하도록강조하여체중감량에도움이될수도있다. 담즙정체또는만성흡수장애증후군환자에서는금기이며, 24 간부전을포함한간손상의예가보고된바가있어미국 FDA에서 orlistat의안전성에대해검토한결과 10년간 4000만명정도의사람들이이약제를사용하였으며이중심각한간손상의예가 13예발견되어 2010년심각한간손상의위험성에대한경고문구를추가하게되었으나 24 orlistat와간손상과의연관성은아직확실하지않다. 25,26 3) 식욕억제를통해에너지섭취를감소시켜체중감량을유도하는약물 (1) 세로토닌을겨냥한약물 Serotonin (5-hydroxytryptophan, 5-HT) 은필수아미노산인 tryptophan에서생성되며호르몬분비, 수면, 체온및식욕의조절, 기분및인지기능등다양한생리적과정및생활습관등에영향을주는신경전달물질이다. 뇌에서의세로토닌농도는섭취한음식내의 tryptophan 및탄수화물양에의해결정된다. 27,28 식이로섭취된 tryptophan은뇌의 raphe nuclei에서 tryptophan hydroxylase에의해 5-hydroxytryptophan 으로전환된후 L-amino acid decarboxylase에의해 decarboxylated되어세로토닌으로된다. 생성된세로토닌은뉴런의시냅스소포내에들어있다가세포외유출 (exocytosis) 에의해시냅스간극 (synaptic cleft) 으로분비된다. 이후세로토닌전달체 (5-HT transporter, 5-HTT or SERT) 에의해시냅스간극으로부터재흡수됨으로써신호전달이종료된다

4 2016 대한간학회추계 Single Topic Symposium 세로토닌은 melanocortin system을통해에너지균형에영향을주게된다. ARC의 POMC 뉴런의 40% 정도가 5-HT 2C receptor (5-HT 2C R) 을발현하고있다 HT는 ARC에서 5-HT 2C R를통해 POMC 뉴런을활성화하여 POMC 뉴런에서 melanocortin 분비를유발하며, 5-HT 1B R를통해 AgRP 뉴런을억제하여음식섭취를줄이게한다. 30,31 이와같은세로토닌의음식섭취에대한효과때문에세로토닌체계에작용하는하는다양한약물들이비만치료제로서시도되어왔다. 이들중 fenfluramine과 dexfenfluramine은세로토닌분비를증가시키고재흡수를방해하는이중효과를보이는비선택적세로토닌작용제로작용한다 이약제들은심장판막질환을유발하여퇴출되었는데, 이는이들약물의일차대사산물인 nordex- 및 norfenfluramine이강력한 5-HT 2B R agnonist로작용하여 35 심장판막에발현되어있는 5-HT 2B R을활성화시키기때문으로생각된다. 또한 sibutramine (Reductil ) 은 noradrenaline and serotonin-reuptake inhibitor로서처음에는항우울제로개발되었으나 1997년비만치료제로서 FDA의승인을받았다. Sibutramine은 1년치료시 4-5 kg의체중감량을유도할뿐아니라혈당이나지질등심장및대사의위험인자의호전도보여주었다. 36,37 그러나혈압및심박수의상승등심혈관질환에대한위험성이제기되었으며, 38 이후 Sibutramine Cardiovascular OUTcomes (SCOUT) trial에서 39 sibutramine 투여군에서심근경색및뇌졸중의발생빈도가높게관찰되어 2010년시장에서퇴출되었다. 따라서현재비만치료제로사용되고있는약물은선택적 5-HT 2c R 작용제인 lorcaserin이유일하다. 40 Lorcaserin (Belviq ) Lorcaserin은 5-HT 2c R에대해 5-HT 2A R에비해 15배, 5-HT 2B R에비해 100배더높은선택성을보여심장판막질환에대한위험성을최소화하였다. 41,42 대규모임상연구인 Behavioral modification and Lorcaserin for Overweight and Obesity Management (BLOOM) trial에서는 1년치료시처음체중에서 5% 이상의체중감소를보인경우가위약군과 lorcaserin군에서각각 5% 와 20.3% 로 lorcaserin군에서더높았으며 (P<0.001), 각군의평균체중감소도위약군의 2.2±0.1 kg에비해 lorcaserin군에서 5.8±0.2 kg로 locaserin군에서더많은체중감량이있었다 (P<0.001). 40 또한, lorcaserin 1년투여시 5% 이상의체중감량을보인환자들에서 2년째에위약또는 lorcaserin을투여한경우체중감량이유지되는경우가위약군에비해 (50.3%) lorcaserin군에서더높았다 (67.9%, P<0.001). 40 치료의효과판정은치료후 3개월때하는것을권장한다. 즉, 치료시작후 3개월에체중이치료전체중에비해 5% 이상감소하지않은경우다른치료로의전환을고려해야한다. Lorcaserin은부작용발생이매우적은안전한약제로알려져있다. 특히비선택적 5-HT 작용제인 fenfluramine과는달리 5-HT 2B R은자극하지않아심장판막질환에는영향을주지않는것으로알려져있다 여명을대상으로한대규모 3상연구에서는대상환자들에서심초음파검사도시행하였는데, 위약군과비교하여판막질환의발생에차이가없었다 대한간학회 The Korean Association for study of the Liver

5 서연석 Anti-obesity medication 이약제는세로토닌증후군의발생위험때문에 monoamine oxidase inhibitor와함께사용하면안된다. 44 세로토닌재흡수억제제나다른세로토닌성약물과의상호작용은연구된바없으나이들약물과함께사용하는경우주의를요한다. 44 (2) 도파민을겨냥한약물음식을섭취하면선조체 (striatum) 에서도파민이분비되어음식섭취에대한만족감을느끼게한다. 45 선조체내의도파민 D1 수용체를자극하면음식섭취가증가하며, 반대로 D2 수용체를자극하면음식섭취가억제된다. 46 또한시상하부에서는도파민이 ARC의 POMC 발현을증가시켜음식섭취를억제한다. 47 도파민과 norepinephrine의재흡수억제제인 bupropion은처음에는항우울제로개발되었으나이후금연보조제로도허가를받았다. 이후연구에서 bupropion이식욕억제및체중감량에효과가있음이관찰되었으나그효과가그리크지는않았는데, 48 이는 POMC에서의 β-endorphin 분비에의한자가억제되먹이고리에의해효과가감소되었기때문으로생각된다. 즉, 시상하부 ARC의 POMC 뉴런은 α -melanocyte-stimulating hormone (α-msh) 뿐아니라 β-endorphin도분비하는데, α-msh는 POMC 뉴런의식욕억제효과를매개하는반면, β-endorphin은 POMC 뉴런의아편유사체길항제를활성화하여자가억제되먹이고리를작용시켜 POMC 뉴런의활성을억제하게되고식욕억제효과를감소시키게되는것으로생각된다. 12 이를극복하기위해 bupropion에 naltrexone을병합한약제가개발되어현재사용되고있다. Naltrexone SR/bupropion SR (Contrave ) 도파민과 norepinephrine의재흡수억제제인 bupropion과아편유사체 (opioid) 수용체길항제로서아편및알코올중독의치료에사용되는 naltrexone 모두식욕억제효과가있으며두약제를병용할때체중감소및내장지방감소에효과적임이증명되었다. 49,50 Bupropion과 naltrexone을병용함으로써 bupropion 이시상하부의 POMC 뉴런을자극하여음식을억제하고 naltrexone이아편유사체-매개 POMC 자가억제를차단하게된다. 51 또한이약제는음식섭취와같은보상행동을조절하는뇌의도파민경로인 mesolimbic reward system에도작용하여식욕억제를유발하는것으로생각된다. 52 여러연구들에서비만의발생에는중추신경계의보상경로에대한조절장애도기여함을시사하였다. 53 비만환자들에서식이조절을하지못하는가장큰이유가음식섭취에대한강한갈망임을볼때 54 니코틴이나아편, 알코올등의중독에대한치료제로사용하는두가지약제가비만치료제로서효과적임은이두약제의작용이중추신경계의보상기전에대한영향이관여할것임을예상할수있다. 이약제는미국과유럽에서각각 2012 년과 2015년에승인되었다. 치료의효과판정은치료후 12주때하는것을권장한다. 즉, 치료시작후 12주까지체중이치료전체중에비해 5% 이상감소하지않은경우다른치료로의전환을고려해야한다. 31

6 2016 대한간학회추계 Single Topic Symposium 흔한부작용으로는구역, 두통, 불면증및변비등이있다. 이약제는혈압및심박수를올릴수있기때문에조절되지않는고혈압환자에서는사용하지않아야하며, 약제투여초기에는주기적으로혈압을감시해야한다. 55 특히심장질환이나뇌혈관질환이있는환자에서는치료시작전에혈압과맥박수를측정해야하며사용중에도, 특히첫 12주간에는, 주기적으로측정해야한다. 그러나약제시판전에시행된 cardiovascular outcome trial의중간분석에서는심혈관질환의증가는관찰되지않았다. 55 약제투여초기에구역등의증상이있을수있으므로수주에걸쳐용량을증량하는것이좋다. Bupropion의경우금연보조제로사용하였을때심한정신과적부작용이발생한예가보고된바있다. 또한이약제는발작을일으킬수있으므로발작장애가있는환자들에서는사용하면안된다. (3) 교감신경계를겨냥한약물 Noradrenalin은신경절이후교감신경뉴런의주된신호전달인자로서이와비슷한약물은교감신경성작용을한다. Noradrenalin 뉴런은외측시상하부로연결되며, 56 α1- 및 β2-adrenoceptors가활성화되면음식섭취가감소하는데, 56 이는 PVN 내의 α1-adrenoceptors가활성화되어음식섭취를억제하기때문으로생각된다. 56 또한뇌간 (brainstem) 내의 noradrenalin 뉴런은세로토닌성뉴런을자극한다. 즉 α1-adrenoceptor agonist와 noradrenalin은 medial raphe nucleus 내의세로토닌성뉴런을자극하여이경로를통해식욕억제효과를나타낼수도있다. 57 이러한기전을통해식욕저하및체중감량을줄이는약제로는암페타민 (amphetamine) 과암페타민유사물질인 phentermine, diethylpropion 및 phenylpropanolamine 등이있다. 이들약제들은 1950년대 ~1960 년대에비만치료제로널리사용되었으나이후심혈관계부작용및중독성에대한우려로시장에서도태또는사장되었으며, 년에는암페타민과이뇨제, digitalis를혼합한약제인 Rainbow pill이소개되었으나심혈관계독성에의한사망을유발하는것으로밝혀져퇴출되었다. 59 현재는 phentermine만이사용되고있다. 메타분석에서는 2-24주치료시위약군에비해 3.6 kg 더많은체중감량을보였다. 60 현재미국에서는중독성및혈압과심박수를증가에따른심혈관부작용을피하기위해 12주이내단기요법으로만을허용하고있으며, 14 유럽에서는더이상이약제의비만치료제로서의사용을허가하지않고있다. 61 Pehntermine/topiramate ER (Qsymia ) 교감신경계약물인 phentermine과항경련제인 topiramate를혼합한제제로 2012년 FDA 승인을받았다. 두약제를병합하는경우체중감량에더효과적이나 62 topiramate가어떤경로로식욕을억제하는지는아직확실하지않다. 치료의효과판정은치료후 3개월때하는것을권장한다. 즉, 치료시작후 3개월까지체중이치료전체중에비해 3% 이상감소하지않은경우다른치료로의전환을고려해야한다. 32 대한간학회 The Korean Association for study of the Liver

7 서연석 Anti-obesity medication Phentermine에의한혈압및심박수의증가, 이에따른심혈관질환위험증가로조절되지않은고혈압또는심장질환이있는환자에서는사용하지않아야한다. 13 또한갑상선기능항진증이있거나 14일이내에 monoamine oxidase inhibitor를복용한환자에서는금기이다. 63 Topiramate는태아의구순열 (oral clefts) 발생과관련이있어 64 약제시작전및치료중매달임신검사를하는것이권장된다. 63 가장흔한부작용으로는이상감각, 어지럼증, 미각이상, 불면증, 변비, 구강건조등이있다. 63 드물게 topiramate가급성근시및녹내장을유발할수있어녹내장환자들에서는금기이다. 63 (4) Liraglutide 3.0 mg (Saxenda ) Liraglutide는 GLP-1과 97% 의구조적동일성을가지면서반감기는더긴 GLP-1 작용제로서당뇨치료에서는 1.8 mg까지사용하고있으며미국과유럽에서는비만치료로 3 mg 투여가허가되어있다 치료의효과판정은치료후 16주때하는것을권장한다. 즉, 치료시작후 16주까지체중이치료전체중에비해 4% 이상감소하지않은경우다른치료로의전환을고려해야한다. 가장흔한부작용으로는구역, 저혈당, 설사, 변비, 구토, 두통, 식욕저하, 피로감, 어지럼증, 복통및혈중 lipase 농도증가등이있다. 구역으로힘들어하는경우가많아, 이를줄이기위해 5주에걸쳐서서히용량을증량해야한다. 69 약간의심박수증가가있을수있으나혈압은대개감소한다. 69 Liraglutide를비롯한 GLP-1 작용제는사람에서는관련성이확실하지않으나동물실험에서갑상선암의발생을증가시켰기때문에수질갑상선암 (medullary thyroid cancer) 의과거력또는가족력이있는환자에서는사용하면안된다. 69 급성췌장염, 담낭질환및당뇨환자에서의저혈당이있을수있으므로주의가필요하다. 임산부에서금기이다. (5) Drugs targeting endocannabinoid system Endocannabinoid system도식욕, 에너지소비, 당및지질대사에중요한역할을한다. 70,71 즉, 대마 (cannabis) 및 cannabinoid (CB) 수용체작용제는음식섭취와체중을증가시키며, 72 반대로 CB1 수용체를억제하면체중이감소하는데 73 시상하부의 endocannabinoid signaling 억제가 leptin의식욕억제효과와관련이있는것으로생각된다. 74 Rimonabant는 endocannabinoid system에서 cannabinoid-1 receptor를차단함으로써체중을감량하는약제로개발되었으며 2006년유럽에서승인되어사용되었다. 이약제에대한 3상실험인 Rimonabant in Obesity (RIO) program에서체중, 허리둘레의현저한감소및심장및대사위험인자의호전이관찰되었다. 75 그러나불안, 우울, 자살충동등정신과적부작용발생이관찰되었다. 76 정신과적부작용은 rimonabant 복용군의 25% 정도에서발생하여위약군에비해 2.5배더높은발생률을보였다. 77 이에대한 FDA 권고를받아들여 2008년시장에서자진철수하였다. 33

8 2016 대한간학회추계 Single Topic Symposium 결론 현재여러가지약제들이비만치료제로사용되고있으며이들약제들중일부는이미국내에서도사용되고있으며다른약제들도대부분국내시판을준비하고있어우리나라에서도비만치료제에대한선택의폭이넓어지고비만환자들에서의체중감량목표도달에도많은도움이될것으로예상된다. 그러나비만은즉시치료하지않으면무서운결과가발생하는위급한질환은아니며대부분의약제가장기간의투여가필요하다는점을고려할때약제의선택에는무엇보다도약제의안전성에무게를두어야할것으로보인다. 적지않은약제들이오랜기간동안효과적이고안전한약제로생각되어사용되다가나중에중대한부작용이증명되어퇴출되는예들을보았을때현재는안전하다고하는약제이더라도부작용에대한세밀한감시를하면서이후발표되는연구결과들에귀를기울여야할것으로생각된다. 또한위에서언급한바와같이각각의약제들마다부작용과금기증이있으므로이를종합적으로고려하여각각의환자들에가장적합하고안전한약제를선택하는것이중요할것으로생각된다. 마지막으로비만치료제는식이요법과운동, 생활습관의개선등을잘할수있도록도와주는보조적인치료제임을강조하며이를계속해서지켜나가도록하는것이중요할것으로생각된다. REFERENCES 1. Fujioka K. Benefits of moderate weight loss in patients with type 2 diabetes. Diabetes Obes Metab 2010;12: Wing RR, Lang W, Wadden TA, Safford M, Knowler WC, Bertoni AG, et al. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care 2011;34: Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA 2014;311: Blundell JE, Levin F, King NA, Barkeling B, Gustafsson T, Hellstrom PM, et al. Overconsumption and obesity: peptides and susceptibility to weight gain. Regul Pept 2008;149: Gautier JF, Chen K, Salbe AD, Bandy D, Pratley RE, Heiman M, et al. Differential brain responses to satiation in obese and lean men. Diabetes 2000;49: Cone RD. Anatomy and regulation of the central melanocortin system. Nat Neurosci 2005;8: Ellacott KL, Cone RD. The role of the central melanocortin system in the regulation of food intake and energy homeostasis: lessons from mouse models. Philos Trans R Soc Lond B Biol Sci 2006;361: Coll AP, Farooqi IS, O'Rahilly S. The hormonal control of food intake. Cell 2007;129: Coll AP. Effects of pro-opiomelanocortin (POMC) on food intake and body weight: mechanisms and therapeutic potential? Clin Sci (Lond) 2007;113: Ilnytska O, Argyropoulos G. The role of the Agouti-Related Protein in energy balance regulation. Cell Mol Life Sci 2008;65: Bagnol D, Lu XY, Kaelin CB, Day HE, Ollmann M, Gantz I, et al. Anatomy of an endogenous antagonist: relationship between Agouti-related protein and proopiomelanocortin in brain. J Neurosci 1999;19:RC Cowley MA, Smart JL, Rubinstein M, Cerdán MG, Diano S, Horvath TL, et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 2001;411: 대한간학회 The Korean Association for study of the Liver

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ÇÐ¼ú°�ÁÂÃÖÀº¿µ 병원약사회지 (2017), 제 34 권제 3 호 J. Kor. Soc. Health-Syst. Pharm., Vol. 34, No. 3, 338 ~ 344 (2017) 학술강좌 비만치료의약물요법 최은영울산대학교병원약제팀 배경 치료계획및목표 비만은건강에위험을초래할수있는비정상적이거나과도한지방축적상태를뜻한다. 지방이많은고칼로리음식의섭취가증가하고, 좌식생활로의변화,