Abstract
Introduction: In the context of obesity pharmacotherapy, some anti-obesity medications (monoamine oxidase inhibitors - MAOIs) have been approved by the Federal Drug Administration (FDA). MAOIs is indicated in combination with lifestyle changes to control overweight and obesity. Some drugs used off-label are accumulating evidence for weight management. Objective: It was to carry out a systematic review to present the off-label pharmacotherapy of obesity through the outcomes of clinical studies. Methods: The present study followed a concise systematic review model (PRISMA). The literary search process was carried out from May to July 2023 and developed based on Web of Science, Scopus, PubMed, Science Direct, Scielo, and Google Scholar, using scientific articles from 2002 to 2023. The low quality of evidence was attributed to case reports, editorials, and brief communications, according to the GRADE instrument. The risk of bias was analyzed according to the Cochrane instrument using the Funnel Plot chart. Results and Conclusion: It was found 132 studies that were submitted to the eligibility analysis and, then, 16 of the 48 total studies were selected. Most studies showed homogeneity in their results, with X2 =95.1% >50%. The Funnel Plot graph showed a symmetrical behavior, not suggesting a significant risk of bias in the studies. Some drugs used off-label are accumulating evidence for weight management. As an example, tirzepatide is a new drug approved by the FDA in May 2022 for the treatment of type 2 diabetes mellitus and can be used off-label for the treatment of obesity. In 2013, the first published study showed that metformin up to a dose of 2500 mg per day is an effective medication to reduce weight. AMPK2 is one of the possible targets of metformin for the treatment of obesity. Although metformin treatment in participants receiving a placebo appears to result in an initial decrease in BMI and HOMA-IR, there is no evidence of a sustained effect after prolonged use in adolescents. Low-certainty evidence suggests that off-label fluoxetine may decrease weight compared with placebo. Sustained-release bupropion was more effective than placebo in weight loss when combined with a 500 kcal deficit diet. Treatment with pramlinitide (up to 240 mg three times daily) for 16 weeks resulted in a placebo-corrected reduction in body weight of 3.7%, and 31% of subjects treated with pramlinitide achieved ≥5% weight loss vs. 2% with placebo. Oral melatonin replacement increases the volume and activity of brown adipose tissue, promoting thermogenesis and adipose tissue metabolism with consequent weight loss.