Abstract
Introduction: Obesity occurs when calorie intake and energy expenditure occur, causing serious comorbidities. According to the Ministry of Health, 52.5% of Brazilians are overweight. A variety of drug classes approved for other indications have been used off-label in attempts to promote weight loss. Objective: It was to carry out a systematic review to list the main drugs used off-label to treat obesity and its comorbidities, as well as present the results of clinical studies. Methods: The PRISMA Platform systematic review rules were followed. The search was carried out from March to April 2025 in the Web of Science, Scopus, Embase, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 110 articles were found, and 29 articles were evaluated in full, and 18 were included and developed in the present systematic review study, out of a total of 20 (2 references are on the website and were not included) Considering the Cochrane tool for risk of bias, the overall evaluation resulted in 21 studies with high risk of bias and 31 studies that did not meet GRADE and AMSTAR-2. Most studies showed homogeneity in their results, with X2=78.8%>50%. Off-label prescribing is very common among doctors who treat obesity. However, randomized controlled studies must be increasingly encouraged and increased to present scientific evidence and, thus, propose a scientific formalism for the safe and effective use of off-label anti-obesity drugs. Naltrexonebupropion was associated with significant improvements in binge eating disorder, with a consistent pattern of weight loss. In people without diabetes, tirzepatide resulted in substantial reductions in body weight (16.5% to 22.4%) over 72 weeks.