Expert Commentary & Five-year View
Given that obesity is the greatest epidemic in human existence (based upon the number of lives affected), it is perhaps surprising that no efficacious pharmacotherapies currently exist. Safety issues with previous weight-loss drugs that led to the discontinuation of fenfluramine, rimonabant and sibutramine may have tempered and perhaps even jaded the enthusiasm for future therapeutics. Because relatively healthy people would need chronic treatment, safety is a leading concern of regulators. However, in the majority of cases, improving the safety margin leads to a reduction in drug efficacy. Thus, what can we expect from this field in the next few years?
In December 2010, a FDA panel approved laparoscopic gastric banding for individuals with a BMI of 35–40 kg/m2 without comorbidities and a BMI of 30–35 kg/m2 with comorbidities. This expansion of the indication for gastric banding may indicate a turning point and the recognition of obesity as a serious chronic disease that is a burden to the healthcare system. Indeed, bariatric surgery is currently the predominant approach to obesity treatment, with the gastric bypass as the most effective procedure available for sustained weight loss and mortality benefit. However, the surgical treatment is limited due to its invasive nature and the high risk of peri- and post-operative complications. Although the mechanisms of long-term weight loss following bariatric surgery are yet to be determined, evidence suggests that the surgical manipulations (the small gastric pouch and exclusion of the duodenum and proximal jejunum) are insufficient to account for the resulting bodyweight loss alone.[157–159] In fact, postoperative changes in eating behavior and appetite have been demonstrated to be related to altered responses of several gut hormones.[46,160]
Therefore, tackling obesity in the future will most likely involve the elucidation of the mechanisms that underlie surgically induced weight loss and the mimicry of the changes in gut hormone profile and neuroendocrine signaling associated with gastric bypass surgery, using pharmacological intervention.
The 'medical bypass' is still a long way off and its achievement will require hard work from both researchers and pharmaceutical industries in the field. The authors are confident that this is a challenge that can, and will, be dealt with successfully in the next decade. We appreciate the surgical option for now, but without a new generation of obesity drugs, a meaningful strike against the obesity epidemic and its associated healthcare costs will prove difficult to achieve.
Financial & competing interests disclosure
The Section of Metabolic Medicine is funded by grants from the Medical Research Council, Biotechnology and Biological Sciences Research Council, National Institute for Health Research (NIHR), an Integrative Mammalian Biology Capacity Building Award and an FP7-HEALTH-2009-241592 EuroCHIP grant, and is supported by the NIHR Imperial Biomedical Research Centre Funding Scheme. Wiebke Fenske is also funded by the German Research Society for a research fellowship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Expert Rev Endocrinol Metab. 2011;6(4):563-577. © 2011 Expert Reviews Ltd.
Cite this: Pharmacotherapy for Obesity - Medscape - Jul 01, 2011.