Unravelling obesity: from leptin to glucagon-like peptide-1 receptor agonists

The global obesity epidemic involves a multifaceted interplay between genetics, environment, and the interactions between them. The discovery of leptin in 1994 changed our understanding of body weight regulation and triggered extensive genetic studies into monogenic and polygenic obesity. Despite initial therapeutic hopes, leptin's efficacy in obesity was limited by leptin resistance. However, glucagon-like peptide-1, an incretin hormone, has become an important tool for managing obesity. Glucagon-like peptide-1 receptor agonists aid in weight loss and glycemic control while also providing metabolic and cardiovascular benefits. This article presents the shift from leptin biology to the therapeutic application of glucagon-like peptide-1 receptor analogs, focusing on their unique mechanisms, gene polymorphisms, and the hormonal interactions that regulate energy homeostasis. It outlines the shift from leptin-based theories to therapies focused on glucagon-like peptide-1 as we have gained understanding of the gut-brain-adipose axis, paving the way for targeted therapies in obesity management.