Title:Current Drug Targets in Obesity Pharmacotherapy – A Review
Volume: 18
Issue: 8
关键词:
肥胖,药物治疗,体重管理,新靶点,病理生理学,抗肥胖药物
摘要: Obesity, an impending global pandemic, is not being effectively controlled by current
measures such as lifestyle modifications, bariatric surgery or available medications. Its toll on health
and economy compels us to look for more effective measures. Fortunately, the advances in biology
and molecular technology have been in our favour for delineating new pathways in the pathophysiology
of obesity and have led to subsequent development of new drug targets. Development of antiobesity
drugs has often been riddled with problems in the past. Some of the recently approved drugs
for pharmacotherapy of obesity have been lorcaserin, phentermine/topiramate and naltrexone/
bupropion combinations. Several promising new targets are currently being evaluated, such as
amylin analogues (pramlintide, davalintide), leptin analogues (metreleptin), GLP-1 analogues (exenatide,
liraglutide, TTP-054), MC4R agonists (RM-493), oxyntomodulin analogues, neuropeptide Y
antagonists (velneperit), cannabinoid type-1 receptor blockers (AM-6545), MetAP2 inhibitors (beloranib),
lipase inhibitors (cetilistat) and anti-obesity vaccines (ghrelin, somatostatin, Ad36). Many of
these groups of drugs act as “satiety signals” while others act by antagonizing orexigenic signals, increasing
fat utilisation and decreasing absorption of fats. Since these targets act through various pathways,
the possibility of combined use of two or more classes of these drugs unlocks numerous
therapeutic avenues. Hence, the dream of personalized management of obesity might be growing
closer to reality.