Background Obesity is a chronic and often relapsing disease that poses serious health risks, leading to increased morbidity and mortality. Semaglutide has now been approved for weight management, providing a promising option for the long-term management of obesity or overweight. This systematic review aimed to summarize the available evidence on the cost-utility of semaglutide in obesity or overweight management. Methods A systematic literature search was conducted from inception to October 28, 2025, using PubMed, EMBASE, Scopus, and Cochrane databases. Titles and abstracts were screened, followed by an eligibility assessment of full texts. The quality of the studies was evaluated using the Quality of Health Economic Studies (QHES) and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklists. Cost-utility results were synthesized using a narrative approach. Results Among 867 articles reviewed, 15 articles underwent full text review, and ultimately, 7 studies met the inclusion and exclusion criteria. The studies included in the analysis indicated that semaglutide provided more Quality-Adjusted Life Years (QALYs) than other anti-obesity medications. The highest incremental cost-utility ratio for semaglutide ($1.1 million/QALY) was reported in the USA. However, due to its higher cost, the Incremental Cost-Utility Ratio (ICUR) exceeded the willingness-to-pay threshold in some cases. Conclusions The current study demonstrates that semaglutide yields a greater number of QALYs but also incurs higher costs compared to phentermine-topiramate, phentermine, and naltrexone-bupropion. Additionally, semaglutide appears to be cost-effective compared to diet and exercise as well as liraglutide. This evidence underscores the potential value of semaglutide in obesity management while highlighting the importance of cost considerations in treatment choices.
