Regulation of Appetite to Treat Obesity

Gilbert W Kim; Jieru E Lin; Michael A Valentino; Francheska Colon-Gonzalez; Scott A Waldman


Expert Rev Clin Pharmacol. 2011;4(2):243-259. 

In This Article

Expert Commentary

A host of technical, institutional and economic issues pose grave challenges to the development and deployment of safe and effective anti-obesity medications. The morbidity and mortality risks accompanying anti-obesity medications have figured prominently in the development of therapeutic agents in this field. Demonstrated safety appears as elusive a goal as it is undeniably a prerequisite for physicians who would prescribe these drugs for their patients, especially in light of the established safety and efficacy of many of the drugs used to treat the comorbidities of obesity. In addition, current drug formulations are often delivered via injection, which represents a serious impediment to patient compliance. Developing orally active drugs is essential to success in this field. Furthermore, most physicians prefer to limit pharmacological therapy to comorbidities, and address obesity through lifestyle modification programs, only employing anti-obesity drugs as a last resort. In that model, patients struggle unsuccessfully for months or years to achieve and maintain adequate weight loss. Earlier administration of anti-obesity pharmacotherapy could provide significant benefit in the reduction of both weight and the risk for the development of comorbidities. Therefore, educating both patients and physicians about the safety and efficacy of these new drugs will be paramount.

Regulatory guidelines for anti-obesity therapy represent a significant obstacle to developing drugs for this application. The FDA mandates that weight control by new drugs must be demonstrated over 1 year to classify a product as efficacious. These efficacy guidelines suggest that: placebo-subtracted weight loss induced by the drug must be ≥5%; and the percentage of drug-treated subjects losing ≥5% of baseline bodyweight must be ≥35% and double the percentage from the placebo-treated subjects. Moreover, at least 3000 subjects must be assigned to the experimental drug with no fewer than 1500 subjects assigned to placebo for a 1-year period to satisfy safety concerns.[200,317] These regulatory guidelines promote drug safety and efficacy and are therefore essential for the responsible and worthwhile development of pharmacotherapy. They nonetheless demand an enormous investment of time and resources from biopharmaceutical companies, and have contributed to the wane of approved anti-obesity drugs that are currently available to physicians and their patients.

Beyond regulatory considerations, there are also financial barriers for patients to consider anti-obesity therapy. Indeed, obesity is not classified as a disease itself, a position propagated by the FDA and its regulatory guidelines. Unfortunately, this position provides insurance companies with a basis to consider anti-obesity drugs with cosmetic procedures as exclusions, and decline patients reimbursement for anti-obesity medications. Thus, patients without an indication for another comorbid condition may have to pay out-of-pocket for anti-obesity therapy. Such costs could represent a major obstacle to patient care, especially in low-income populations with disproportionately high obesity rates. In that context, a 1-month supply of orlistat, for example, costs approximately US$120–140, a major hurdle for patients of low economic status.


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