Pharmacotherapies for Obesity: Past, Current, and Future Therapies

Abstract

Past therapies for the treatment of obesity have typically involved pharmacological agents usually in combination with a calorie-controlled diet. This paper reviews the efficacy and safety of pharmacotherapies for obesity focusing on drugs approved for long-term therapy (orlistat), drugs approved for short-term use (amfepramone [diethylpropion], phentermine), recently withdrawn therapies (rimonabant, sibutamine) and drugs evaluated in Phase III studies (taranabant, pramlintide, lorcaserin and tesofensine and combination therapies of topiramate plus phentermine, bupropion plus naltrexone, and bupropion plus zonisamide). No current pharmacotherapy possesses the efficacy needed to produce substantial weight loss in morbidly obese patients. Meta-analyses support a significant though modest loss in bodyweight with a mean weight difference of 4.7 kg (95% CI 4.1 to 5.3 kg) for rimonabant, 4.2 kg (95% CI 3.6 to 4.8 kg) for sibutramine and 2.9 kg (95% CI 2.5 to 3.2 kg) for orlistat compared to placebo at ≥12 months. Of the Phase III pharmacotherapies, lorcaserin, taranabant, topiramate and bupropion with naltrexone have demonstrated significant weight loss compared to placebo at ≥12 months. Some pharmacotherapies have also demonstrated clinical benefits. Further studies are required in some populations such as younger and older people whilst the long term safety continues to be a major consideration and has led to the withdrawal of several drugs.

Recent advancements in drug treatment of obesity

“…18 Two anti-obesity drugs have been approved by NICE but subsequently withdrawn: Rimonabant in 2009 4 and Sibutramine in 2010. 13 …”

Treatments for Hypertension in Type 2 Diabetes-Non-Pharmacological and Pharmacological Measurements

“…Lorcaserin, taranabant, topiramate and bupropion with naltrexone are currently on phase III trials with demonstrated significant weight loss compared to placebo at more than 12 months. Some pharmacotherapies have also demonstrated clinical benefits without any side effects, however, further studies are required for a long-term safety [86]. Recently, contrave, a combination of two approved drugs of bupropio and naltrexone, completed Phase III trials with significant weight loss and was approved by FDA in 2010, but FDA declined to approve contrive due to serious cardiovascular adverse events in 2011 [86].…”

“…Some pharmacotherapies have also demonstrated clinical benefits without any side effects, however, further studies are required for a long-term safety [86]. Recently, contrave, a combination of two approved drugs of bupropio and naltrexone, completed Phase III trials with significant weight loss and was approved by FDA in 2010, but FDA declined to approve contrive due to serious cardiovascular adverse events in 2011 [86]. Importantly, obesity is, at least, in part, determined by genetic backgrounds [87], suggesting that a genetic approach to limiting obesity may find a place in the future.…”

Glucagon increases energy expenditure independently of brown adipose tissue activation in humans

“…Currently licensed drugs, generally aimed at either reducing intestinal fat absorption (such as intestinal lipase inhibitors) or inhibiting appetite (such as phentermine), have limited weight loss efficacy on their own. Anti-obesity agents which elevate EE by stimulating the sympathetic nervous system have produced dangerous side effects, particularly cardiovascular morbidity [2][3][4]. There is a great unmet need for drugs that can safely inhibit appetite and increase EE.…”