Animal models for development of anti-obesity drugs in the Age of GLP-1 Agents

Obesity is a major health crisis globally, with prevalence escalating significantly in recent decades. Obesity is not merely excessive weight but is associated with myriad health complications. Ensuring the translational effectiveness of pre-clinical obesity models is paramount, and the success of GLP-1 therapies has highlighted important benchmarks for guiding drug development. The authors discuss the status of various animal models used for the development of anti-obesity drugs, with particular emphasis on rodent models and their validity of preclinical-to-clinical translation. They also highlight innovative animal model integration opportunities between obesity and other associated pathology. The article is based on literature searches using PubMed for content (up until February 2025). The effectiveness of GLP-1 therapies in treating type 2 diabetes and obesity presents an opportunity to evaluate the translational relevance of animal models of obesity. Due to their compelling safety profiles, GLP-1(s) are being tested in a wide range of obesity-associated diseases. Optimization of the mechanistic qualities in this drug class requires the incorporation of new endpoints beyond body weight, including lean mass preservation, cardiovascular health, and anti-inflammatory activities. Finally, we are compelled by the intersection of non-obesity disease models into an obesogenic framework to understand the combinatorial effects of obesity on these other disease indications, including heart failure, neurodegenerative diseases, and cancer.