New Targets for Drug Treatment of Obesity

Annu Rev Pharmacol Toxicol. 2017 Jan 6:57:585-605. doi: 10.1146/annurev-pharmtox-010716-104735.

Abstract

Antiobesity medical management has shown unsatisfactory results to date in terms of efficacy, safety, and long-term maintenance of weight loss. This poor performance could be attributed to the complexity of appetite regulation mechanisms; the serious drug side effects; and, crucially, the lack of profile-matching treatment strategies and individualized, multidisciplinary follow-up. Nevertheless, antiobesity pharmacotherapy remains a challenging, exciting field of intensive scientific interest. According to the latest studies, the future of bariatric medicine lies in developing drugs acting at multiple levels of the brain-gut axis. Currently, research is focused on the generation of combination treatments based on gut hormones in a way that mimics changes underlying surgically induced weight loss, in addition to centrally acting agents; these aim to restore energy balance disruptions and enhance energy expenditure. Collectively, the pharmacological resolution of obesity could potentially be achieved with combination regimens targeting different molecules and levels of the energy homeostasis system, in parallel with matching patients' needs, resulting in a favorable metabolic profile.

Keywords: adiposity; amylin; energy homeostasis; glucagon-like peptide 1; hypothalamus; leptin.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Obesity Agents / administration & dosage
  • Anti-Obesity Agents / metabolism*
  • Appetite Regulation / drug effects
  • Appetite Regulation / physiology
  • Drug Delivery Systems / methods
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology
  • Gastrointestinal Hormones / administration & dosage
  • Gastrointestinal Hormones / metabolism*
  • Humans
  • Obesity / drug therapy*
  • Obesity / metabolism*
  • Peptide Hormones / administration & dosage
  • Peptide Hormones / metabolism
  • Treatment Outcome

Substances

  • Anti-Obesity Agents
  • Gastrointestinal Hormones
  • Peptide Hormones