IntroductionDiabetes related foot ulcers (DFUs) are common complications of type 2 diabetes mellitus (T2DM), affecting 15-25% of individuals living with diabetes and significantly contributing to healthcare costs ($9-13 billion annually in the U.S.). Without effective management, these wounds often lead to severe outcomes like amputations. This study aims to examine the association of semaglutide on DFU management.MethodsThis retrospective cohort study utilized TriNetX US Research Network data to assess the impact of semaglutide, a GLP-1 receptor agonist, on DFU outcomes between 2013 and 2023. The study compared outcomes between semaglutide users with DFU (Cohort A,= 6329) and non-users with DFU (Cohort B,= 118,821) across 64 healthcare organizations. We matched participants by age, gender, race, and ethnicity; however, we excluded patients with certain co-morbidities. Statistical analysis, such as chi-square analysis and risk ratio, using TriNetX software evaluated different complication outcomes.ResultsSemaglutide users with DFU demonstrated lower relative risks for complications compared to non-users. Within 1 year, semaglutide users were associated with lower relative risks for wound healing complications (0.19% vs 0.38%), chronic non-healing wounds (0.75% vs 1.23%), chronic pain (4.44% vs 8.06%), wound care (2.42% vs 4.86%), wound dehiscence (0.26% vs 0.56%), and amputation (2.34% vs 5.21%) (< .05). Similar trends persisted over 5 years. While these findings highlight potential benefits of semaglutide with patients with DFU, causation cannot be inferred due to the study's observational design.ConclusionSemaglutide use was associated with favorable outcomes in patients with diabetes-related foot ulcers, including reductions in wound-related complications. While these findings suggest potential benefits of semaglutide as an adjunct in DFU management, further research is needed to confirm these associations and to better understand the mechanisms involved.