Citation

Kim GW, Lin JE, Blomain ES, Waldman SA. Clin. Pharmacol. Ther. 2014; 95(1): 53-66.

Copyright

(Copyright © 2014, American Society for Clinical Pharmacology and Therapeutics, Publisher Nature Publishing Group)

DOI

10.1038/clpt.2013.204

PMID

unavailable

Abstract

Obesity is a growing pandemic, and related health and economic costs are staggering. Pharmacotherapy, partnered with lifestyle modifications, forms the core of current strategies to reduce the burden of this disease and its sequelae. However, therapies targeting weight loss have a significant history of safety risks, including cardiovascular and psychiatric events. Here, evolving strategies for developing antiobesity therapies, including targets, mechanisms, and developmental status, are highlighted. Progress in this field is underscored by Belviq (lorcaserin) and Qsymia (phentermine/topiramate), the first agents in more than 10 years to achieve regulatory approval for chronic weight management in obese patients. On the horizon, novel insights into metabolism and energy homeostasis reveal guanosine 3',5'-cyclic monophosphate (cGMP) signaling circuits as emerging targets for antiobesity pharmacotherapy. These innovations in molecular discovery may elegantly align with practical off-the-shelf approaches, leveraging existing approved drugs that modulate cGMP levels for the management of obesity.

Language: en

Keywords

human; suicide; quality of life; nephrotoxicity; exercise; abdominal pain; suicidal ideation; depression; anxiety; amphetamine; obesity; fatigue; pancreatitis; article; anorexia; vomiting; mental disease; sexual dysfunction; fenfluramine; weight reduction; drug metabolism; amfebutamone; cognitive defect; xerostomia; unclassified drug; fear; priority journal; headache; constipation; drug mechanism; signal transduction; heart infarction; nonhuman; sudden death; drug safety; food and drug administration; cerebrovascular accident; health care cost; drug dependence; drug efficacy; diarrhea; nausea; tremor; restlessness; amphetamine derivative; cardiovascular disease; hypertension; topiramate; cardiovascular effect; withdrawal syndrome; infection; leptin; arthralgia; brain hemorrhage; liver toxicity; hypoglycemia; drug approval; heart palpitation; nervousness; bradycardia; nephrolithiasis; dizziness; tetrahydrolipstatin; hyperhidrosis; priapism; sibutramine; phenylpropanolamine; sinusitis; drug targeting; pulmonary hypertension; valvular heart disease; lifestyle modification; exendin 4; pramlintide; randomized controlled trial (topic); rimonabant; antiobesity agent; energy metabolism; oxyntomodulin; steatorrhea; phentermine; excitability; desvenlafaxine; amfebutamone plus naltrexone; lorcaserin; phentermine plus topiramate; cetilistat; liraglutide; appetite stimulant; multicenter study (topic); eating habit; phase 2 clinical trial (topic); phase 3 clinical trial (topic); phase 1 clinical trial (topic); sudden cardiac death; cyclic GMP; davalintide; lipid absorption; metreleptin; osymia; pipeline; velneperit