Latest approaches for the treatment of obesity

Abstract

Introduction: Obesity is a body weight disorder characterized by excess adiposity that increases the risk for developing co-morbidities such as type 2 diabetes. A large medical need exists for new anti-obesity treatments capable of promoting 10% or greater weight loss, with minimal side effects.

Areas covered: The authors describe the application of monogenic forms of rare obesity and genome-wide association studies in selecting critical pathways for drug discovery. Furthermore, they review in detail several pathways and pharmacological targets in the central nervous system (e.g., the leptin-melanocortin axis, the opioid system, GLP-1/GLP-1 system, and FGF21/FGFR1c/β-Klotho axis) that play an important role in the regulation of feeding behavior and energy homeostasis. Special focus is given to new strategies that engage well-known targets via novel mechanisms in order to circumvent issues seen with previous drug candidates that failed in the clinic. Finally, the authors discuss the recent developments around fixed-dose combinations, targeted polypharmacology, and non-traditional combinations of drugs and devices.

Expert opinion: The future for new weight-loss approaches to treat obesity looks promising. Current therapies have shown modest effects on weight loss in the general obese population but will have greater impact in smaller homogeneous sub-populations of obese subjects using personalized medicine. Drug combinations that target multiple, complementary pathways have the potential to promote double-digit weight loss in a broader, heterogeneous patient population. Furthermore, the development of advanced subcutaneous delivery technologies has opened up opportunities to develop breakthrough peptide and biologic agents for the treatment of obesity.

Keywords:

• central nervous system
• devices
• FGF21
• FGFR1c/β-Klotho
• GLP-1
• GLP-1R
• LepRb
• leptin system
• MC4R
• melanocortin system
• microbiome
• obesity

Declaration of interest

The authors are all employees of Pfizer, Inc. 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.

Notes

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