Abstract
Introduction: According to the World Atlas of Obesity, overweight and obesity will affect nearly 3 billion adults (approximately 50% of the global adult population) by 2030. Melatonin therapy (MEL) and its pharmacological analogues are notable therapeutic agents for treating various pathologies, including obesity, metabolic diseases, and diabetes. Objective: A meta-analysis of melatonin therapy in the treatment of patients with obesity and meta-inflammation was conducted. Methods: The PRISMA systematic review guidelines were followed. Randomized clinical trials, prospective studies, and retrospective studies were included in the analysis. The literature search was conducted from July to August 2025 and was based on Web of Science, Scopus, Embase, PubMed, Lilacs, Ebsco, Scielo, and Google Scholar, covering scientific articles from various periods to the present. Results and Conclusion: Eighteen clinical studies with 4,678 participants were selected for this meta-analysis. According to the GRADE instrument, most studies presented homogeneous results, with X2=96.8%>50%. Considering the Cochrane risk of bias tool, the overall assessment resulted in 20 studies with a high risk of bias and 24 studies that did not meet the GRADE and AMSTAR-2 criteria. It was concluded that melatonin supplementation with an average of 5.0 mg significantly reduced body weight and reduced comorbidities in patients with obesity and meta-inflammation. Melatonin also regulates food intake, regulating the production and secretion of insulin, glucagon, and cortisol, and plays an important role in insulin signaling, with its deficiency having diabetogenic effects.