Current Drug Targets in Obesity Pharmacotherapy – A Review

Abstract

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.

<p>Healthy Eating, Physical Activity, and Sleep Hygiene (HEPAS) as the Winning Triad for Sustaining Physical and Mental Health in Patients at Risk for or with Neuropsychiatric Disorders: Considerations for Clinical Practice</p>

“…The medical-surgical world is increasingly oriented towards drug-or surgeon-centered treatments. Obesity is treated with anti-obesity medications or bariatric surgery, 143,144 insomnia with transcranial magnetic stimulation, 145 and treatmentresistant conditions with neurosurgical implants. 146 It seems that multiple benefits deriving from healthy diet, physical activity, and restful sleep have been progressively forgotten.…”

Anti-Obesity Drugs: Long-Term Efficacy and Safety: An Updated Review

“…To date, however, there has been no approved combination agent for obesity management, besides phentermine/ topiramate and naltrexone/bupropion. Other co-administered medications have been investigated to elucidate their long-term efficacy and adverse events [15,16]. Most combinations primarily focus on both controlling hunger/appetite/satiety and inhibiting peripheral calorie absorption (i.e., phentermine/sodium glucose co-transporter 2 [SGLT-2] inhibitor, a GLP-1 agonist/other gut hormones, or an SGLT-2 inhibitor).…”

“…Currently, most guidelines recommend pharmacotherapy as a second-line treatment for weight management after lifestyle modification [13,14]. In fact, numerous medications have been developed for the long-term management of obesity, with different mechanisms targeting various factors and diverse pathways that might cause a positive energy balance [15]. During the last decades, some anti-obesity drugs have been used to treat morbid obesity; however, most of these have been removed from the market owing to serious longterm side effects, particularly cardiovascular-related issues [16].…”

Single Oral Acute Toxicity of Banhasasim‐Tang and Its Antiobesity Effect on Diet‐Induced Obese Mice and 3T3‐L1 Adipocytes

“…Orlistat, used as a positive control, is only one drug for long-term treatment of obesity. But the weight-loss effect of Orlistat is mild [ 29 , 30 ]. In the present study, Orlistat did not affect the body weight and white adipose tissue weight in HFD-induced obese mice.…”