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Weight Loss Agents

Abstract
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. 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was approved in the United States in 1997 and used widely for several years in the United States, but was then withdrawn in 2010 because of concerns over increased risks for cardiovascular adverse events including myocardial infarction and stroke. Lorcaserin (Belviq), a serotonin agonist, was approved as a weight loss agent in 2012 but was withdrawn in 2020 because of concerns of increased risk for cancer.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). 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).

Publisher

National Institute of Diabetes and Digestive and Kidney Diseases
Bethesda (MD)

Language

eng

PubMed ID

31644235

Citation

Weight Loss Agents. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases, 2012, Bethesda (MD).
Weight Loss Agents. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases; 2012.
(2012). Weight Loss Agents. In LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases
Weight Loss Agents. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012.
* Article titles in AMA citation format should be in sentence-case
TY - CHAP T1 - Weight Loss Agents BT - LiverTox: Clinical and Research Information on Drug-Induced Liver Injury Y1 - 2012/// PY - 2019/10/24/pubmed PY - 2019/10/24/medline PY - 2019/10/24/entrez N2 - 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. 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). 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). PB - National Institute of Diabetes and Digestive and Kidney Diseases CY - Bethesda (MD) UR - https://www.unboundmedicine.com/medline/citation/31644235/LiverTox:_Clinical_and_Research_Information_on_Drug-Induced_Liver_Injury:_Weight_Loss_Agents L2 - https://www.ncbi.nlm.nih.gov/books/NBK548929 DB - PRIME DP - Unbound Medicine ER -
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