Future Pharmacotherapy for Obesity: New Anti-obesity Drugs on the Horizon
Purpose of Review
Obesity is a global health crisis with detrimental effects on all organ systems leading to worsening disease state and rising costs of care. Persons with obesity failing lifestyle therapies need to be escalated to appropriate pharmacological treatment modalities, medical devices, and/or bariatric surgery if criteria are met and more aggressive intervention is needed. The progression of severe obesity in the patient population coupled with related co-morbidities necessitates the development of novel therapies for the treatment of obesity. This development is preceded by increased understanding of the underpinnings of energy regulation and neurohormonal pathways involved in energy homeostasis.
Though there are approved anti-obesity drugs available in the USA, newer drugs are now in the pipeline for development given the urgent need. This review focuses on anti-obesity drugs in the pipeline including centrally acting agents (setmelanotide, neuropeptide Y antagonist [velneperit], zonisamide-bupropion [Empatic], cannabinoid type-1 receptor blockers), gut hormones and incretin targets (new glucagon-like-peptide-1 [GLP-1] analogues [semaglutide and oral equivalents], amylin mimetics [davalintide, dual amylin and calcitonin receptor agonists], dual action GLP-1/glucagon receptor agonists [oxyntomodulin], triple agonists [tri-agonist 1706], peptide YY, leptin analogues [combination pramlintide-metreleptin]), and other novel targets (methionine aminopeptidase 2 inhibitor [beloranib], lipase inhibitor [cetilistat], triple monoamine reuptake inhibitor [tesofensine], fibroblast growth factor 21), including anti-obesity vaccines (ghrelin, somatostatin, adenovirus36).
With these new drugs in development, anti-obesity therapeutics have potential to vastly expand allowing better treatment options and personalized approach to obesity care.
KeywordsAnti-obesity drugs Weight loss medications Novel targets Phase 1 and phase 2 trials Obesity pharmacotherapy Weight management
The authors thank A. McCarthy for editorial and administrative assistance.
No funding was provided for the drafting of this manuscript.
Compliance with Ethical Standards
Conflict of Interest
Gitanjali Srivastava has received compensation from Rhythm Pharmaceuticals for service on an advisory board.
Caroline Apovian has received research funding through grants from Orexigen, Aspire Bariatrics, GI Dynamics, MYOS, Takeda, Gelesis, Vela Foundation, Dr. Robert C. and Veronica Atkins Foundation, Coherence Lab, Energesis, Patient-Centered Outcomes Research Institute (PCORI), and the National Institutes of Health (NIH); has received compensation from Nutrisystem, Zafgen, Sanofi-Aventis, Orexigen, Novo Nordisk, GI Dynamics, Takeda, Scientific Intake, Gelesis, Merck, and Johnson & Johnson for service on advisory boards; and owns stock in Science-Smart LLC.
GS reports personal fees from Rhythm Pharmaceuticals, outside the submitted work. Dr. Apovian reports personal fees from Nutrisystem, personal fees from Zafgen, personal fees from Sanofi-Aventis, grants and personal fees from Orexigen, personal fees from NovoNordisk, grants from Aspire Bariatrics, grants and personal fees from GI Dynamics, grants from Myos, grants and personal fees from Takeda, personal fees from Scientific Intake, grants and personal fees from Gelesis, other from Science-Smart LLC, personal fees from Merck, personal fees from Johnson & Johnson, grants from Vela Foundation, grants from Dr. Robert C. and Veronica Atkins Foundation, grants from Coherence Lab, grants from Energesis, grants from PCORI, and grants from NIH, outside the submitted work. However, the authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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