Obesity is an increasingly growing public health issue affecting a substantial proportion of the population in the United States. This condition increases the risk for multiple disease processes, including cardiometabolic disorders, osteoarthritis, gout, respiratory issues, reproductive problems, and some cancers. Glucagon-like peptide-1 (GLP-1) receptor agonists got their first US Food and Drug Administration (FDA) approval in 2005 in the form of exenatide for type 2 diabetes mellitus (T2DM) management. Thereafter, GLP-1 analogs have been increasingly studied as a noninvasive strategy for weight reduction, and they transitioned from diabetes-only therapies to weight management with the approval of once-daily liraglutide prior to weekly semaglutide formulation in 2021. In essence, GLP-1 receptor agonists have emerged as a promising drug for long-lasting weight reduction and blood glucose control for patients with or without type 2 diabetes mellitus, surpassing traditional methods such as lifestyle changes and bariatric surgery. Oral Wegovy (Rybelsus) was approved for T2DM management in 2020; however, it is approved for weight loss after the recent publication of Oral Semaglutide in Adults with Overweight or Obesity (OASIS). This literature review will discuss and summarize weight loss results from OASIS trials 1, 2, 3, and 4. The OASIS 1 and 2 trials compared the therapeutic efficacy and clinical safety profile of once-daily oral semaglutide 50 mg versus placebo on overweight and obese participants without T2DM and both with and without T2DM, respectively. The OASIS 3 trial assessed the therapeutic efficacy and clinical safety profile of once-daily oral semaglutide 50 mg versus placebo in 200 Chinese adults who were obese and overweight with one or more weight-related comorbidities, including T2DM. The OASIS 4 trial evaluated the safety and effectiveness of once-daily semaglutide 25 mg in obese and overweight patients without T2DM. Clinical trial data and relevant literature were retrieved through database searches of the National Center for Biotechnology Information and ClinicalTrials.gov. The OASIS 1, 2, and 4 demonstrated that oral semaglutide has superior efficacy compared to placebo in body weight loss, which helped secure FDA approval for oral Wegovy. Though OASIS 3 is registered in clinical trials, the results of OASIS 3 have not been published in a peer-reviewed journal yet.
