Obesidade como Doença Endócrino-Metabólica: Da Fisiopatologia às Inovações Terapêuticas

Abstract

Introduction:  Obesity is a chronic, multifactorial, and progressive disease of endocrine-metabolic origin, whose increasing prevalence represents one of the greatest global public health challenges. Recent advances in the understanding of the gut–brain hormonal axis have revolutionized the pharmacological treatment of obesity, offering new therapeutic perspectives with significant metabolic and cardiovascular impacts.Objective:
 To critically analyze the evolution of incretin-based therapies and their effects on weight loss, metabolic control, and cardiovascular risk modification, highlighting the main advances, limitations, and future perspectives in obesity management. Methodology:  A narrative literature review was conducted using the PubMed, Scopus, and SciELO databases, including randomized clinical trials, meta-analyses, and systematic reviews published between 2015 and 2024. Studies evaluating the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dual agonists (GIP/GLP-1), and emerging combination therapies were selected. Results: Pivotal clinical trials demonstrate that GLP-1 RAs, such as liraglutide and semaglutide, and dual agonists, such as tirzepatide, achieve weight loss exceeding 15% of initial body weight and significantly reduce cardiovascular risk, independently of glycemic control. These findings redefine obesity treatment as a cardiometabolic disease–modifying intervention. However, withdrawal studies reveal weight regain after treatment cessation, associated with a robust counter-regulatory hormonal and metabolic response, underscoring the need for continuous therapy. Conclusion: The management of obesity requires a chronic, multimodal, and personalized approach that integrates incretin-based pharmacotherapies with sustained behavioral and nutritional interventions. The future of obesity treatment lies in innovative combinations of multi-agonist agents and long-term strategies aimed not only at weight control but also at global cardiovascular and metabolic risk modification.