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<meta name="citation_inbook_title" content="LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]">
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<meta name="citation_title" content="Weight Loss Agents">
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<meta name="citation_publisher" content="National Institute of Diabetes and Digestive and Kidney Diseases">
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<meta name="citation_date" content="2020/06/05">
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yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK548929_"><span class="title" itemprop="name">Weight Loss Agents</span></h1><p class="fm-aai"><a href="#_NBK548929_pubdet_">Publication Details</a></p></div></div><div class="body-content whole_rhythm" itemprop="text"><div id="WeightLossAgents.OVERVIEW"><h2 id="_WeightLossAgents_OVERVIEW_">OVERVIEW</h2><p>While many agents have been developed to aid in weight loss, few have withstood critical assessment of safety and efficacy. Weight loss agents are held to a high standard for safety and tolerability, because they are often used by otherwise healthy individuals driven more by concerns over appearance than health. Furthermore, all weight loss medications should be used as a part of a coordinated weight loss program that includes modification of behaviors, a reduced calorie diet and increased physical activity or exercise.</p><p>Drugs for weight loss can be separated into those that suppress appetite (such as diethylpropion and phentermine) and those that block absorption of calories (orlistat). The anorexic agents that have been used for weight loss include sympathomimetic agents (such as diethylpropion, and phentermine), serotonin and norepinephrine reuptake inhibitors (bupropion, fluoxetine, sibutramine), serotonin agonists (lorcaserin), GABAergic agents (topiramate, zonisamide) and cannabinoid antagonists (rimonabant). The cannabinoid antagonist rimonabant was shown to induce weight loss but was never approved in the United States because of concerns over suicidal ideation and behaviors associated with its use. Sibutramine (Meridia) which has both sympathomimetic activity as well as serotonin and norepinephrine reuptake inhibitory activity, was approved in the United States in 1997 and used widely for several years in the United States, but was then withdrawn in 2010 because of concerns over increased risks for cardiovascular adverse events including myocardial infarction and stroke. Lorcaserin (Belviq), a serotonin agonist, was approved as a weight loss agent in 2012 but was withdrawn in 2020 because of concerns of increased risk for cancer. Second generation weight loss agents still in current use include the combination of phentermine and topiramate (Qsymia: 2012); a fixed dose combination of the antidepressant bupropion and the opioid receptor antagonist naltrexone (Contrave: 2014); and the injectable glucagon-like peptide-1 (GLP-1) agonist liraglutide which is approved and used for type 2 diabetes (Victoza: 20xx) and, when given in a higher dose, for weight loss (Saxenda:2014).</p><p>Drugs that suppress appetite generally affect appetite centers in the central nervous system (CNS) and can have other CNS effects such as nervousness, excitability, insomnia, mood changes, and headache. Drugs that affect absorption of nutrients often have other gastrointestinal side effects such as diarrhea, flatulence and abdominal bloating. Liver injury is rare with all of the currently approved medications for weight loss. In contrast, serious hepatotoxicity has been linked to several over the counter and herbal preparations promoted as helping with weight loss (usnic acid, ephedra, green tea, and Garcinia cambogia).</p><p>The following weight loss agents are discussed individually:</p><ul><li class="half_rhythm"><div>
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<a href="/books/n/livertox/Bupropion/?report=reader">Bupropion</a>
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</div></li><li class="half_rhythm"><div>
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<a href="/books/n/livertox/Diethylpropion/?report=reader">Diethylpropion</a>
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</div></li><li class="half_rhythm"><div>
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<a href="/books/n/livertox/Liraglutide/?report=reader">Liraglutide</a>
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</div></li><li class="half_rhythm"><div>
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<a href="/books/n/livertox/Lorcaserin/?report=reader">Lorcaserin</a>
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</div></li><li class="half_rhythm"><div>
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<a href="/books/n/livertox/Naltrexone/?report=reader">Naltrexone</a>
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</div></li><li class="half_rhythm"><div>
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<a href="/books/n/livertox/NaltrexoneBupropion/?report=reader">Naltrexone-Bupropion</a>
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</div></li><li class="half_rhythm"><div>
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<a href="/books/n/livertox/Orlistat/?report=reader">Orlistat</a>
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</div></li><li class="half_rhythm"><div>
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<a href="/books/n/livertox/Phentermine/?report=reader">Phentermine</a>
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</div></li><li class="half_rhythm"><div>
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<a href="/books/n/livertox/PhentermineTopiramat/?report=reader">Phentermine-Topiramate</a>
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</div></li><li class="half_rhythm"><div>
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<a href="/books/n/livertox/Sibutramine/?report=reader">Sibutramine</a>
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</div></li></ul></div><div id="WeightLossAgents.ANNOTATED_BIBLIOGRAPHY"><h2 id="_WeightLossAgents_ANNOTATED_BIBLIOGRAPHY_">ANNOTATED BIBLIOGRAPHY</h2><p>References updated: 06 June 2020</p><ul class="first-line-outdent"><li><div class="bk_ref" id="WeightLossAgents.REF.kang.2012.13">Kang JG, Park CY. Anti-obesity drugs: a review about their effects and safety. <span><span class="ref-journal">Diabetes Metab J. </span>2012;<span class="ref-vol">36</span>:13–25.</span> [<a href="/pmc/articles/PMC3283822/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3283822</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22363917" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22363917</span></a>]<div>
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<i>(Review of the safety and efficacy of current and potentially future medications for obesity; mentions that phentermine has been available for 50 years, but there is little data on its long term efficacy and safety).</i>
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</div></div></li><li><div class="bk_ref" id="WeightLossAgents.REF.yanovski.2014.74">Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. <span><span class="ref-journal">JAMA. </span>2014;<span class="ref-vol">311</span>:74–86.</span> [<a href="/pmc/articles/PMC3928674/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3928674</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24231879" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24231879</span></a>]<div>
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<i>(Systematic review of the literature on the efficacy of long term use of drugs for obesity that were FDA approved [at the time of the analysis] mentions that phentermine, diethylpropion and phendimetrazine are approved for short term use only, but that orlistat, lorcaserin and phentermine/topiramate are approved for long term use although their efficacy is modest; no discussion of hepatotoxicity).</i>
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</div></div></li><li><div class="bk_ref" id="WeightLossAgents.REF3">Diet, drugs, devices, and surgery for weight management. <span><span class="ref-journal">Med Lett Drugs Ther. </span>2018;<span class="ref-vol">60</span>(1548):91–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29913463" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29913463</span></a>]<div>
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<i>(Concise review of the medical and surgical therapies for obesity mentions that orlistat is modestly effective in inducing weight loss and that “severe liver injury has been reported rarely, but no cause-and-effect relationship has been established”; discussion of other weight loss agents [phentermine/topiramate, naltrexone/bupropion, lorcaserin and liraglutide] does not mention ALT elevations or hepatotoxicity).</i>
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</div></div></li><li><div class="bk_ref" id="WeightLossAgents.REF.saunders.2018.135">Saunders KH, Umashanker D, Igel LI, Kumar RB, Aronne LJ. Obesity pharmacotherapy. <span><span class="ref-journal">Med Clin North Am. </span>2018;<span class="ref-vol">102</span>:135–48.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/29156182" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29156182</span></a>]<div>
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<i>(Review of the pharmacotherapy of obesity focusing upon the 6 most commonly used medications, discusses the common side effects of the agents, but does not discuss hepatotoxicity).</i>
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</div></div></li></ul></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK548929_pubdet_">Publication Details</h2><h3>Publication History</h3><p class="small">Last Update: <span itemprop="dateModified">June 5, 2020</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="https://www.niddk.nih.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Institute of Diabetes and Digestive and Kidney Diseases</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Weight Loss Agents. [Updated 2020 Jun 5].<span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/livertox/Warfarin/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/livertox/WilsonDiseaseAgents/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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