Approaches to the Pharmacological Treatment of Obesity

Victoria Salem; Stephen R Bloom

Disclosures

Expert Rev Clin Pharmacol. 2010;3(1):73-88. 

In This Article

Five Year View

The stage is set for the continued rise in the prevalence of obesity and its associated morbidities. While lifestyle interventions at personal and societal levels are of the utmost importance, the need for better tolerated and more efficacious pharmacotherapies is undoubted. Important historical lessons have been learned from drugs designed to interact with receptors and neurotransmitters involved in the complicated circuitry of energy homeostasis and appetitive behavior, which overlap with several other higher functions, resulting in unwanted effects such as mood disturbance. A more detailed understanding of the physiological control of energy balance and the pathophysiology of obesity will continue to inform the development of highly selective, better targeted compounds. Energy homeostasis is of such critical physiological importance that there exists much redundancy and compensatory mechanisms within the system. This is compounded by the tendency to protect against weight loss much more avidly than weight gain. As more drugs become available, a polypharmacy approach, possibly alongside shifting dosing schedules, will develop to overcome these problems. This may be further aided by the greater understanding of the genetic influences on obesity, such as receptor polymorphisms, which would allow for individually tailored combinations. As natural activators of satiety circuits on a daily basis, gut hormones are likely to be an ongoing area of intense research in the field of anti-obesity drug development. There is impetus towards the realistic goal of using combination gut hormone therapy to produce a 'medical bypass' – achieving the outstanding weight loss and health benefits of gastric bypass surgery without its associated risks. Future advances in this field will include the development of long acting peptide hormone analogs to overcome the problem of the very short plasma half-life of endogenous peptide hormones, and the introduction of new forms of delivery: slow-release injectable depots, protease-resistant oral formulations, inhalation devices and transdermal patches.

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