Abstract
Background. Oral mucositis is a major toxicity of hematopoietic stem-cell transplantation (HSCT). Glucagon-like peptide-1 (GLP-1) signaling promotes epithelial repair and attenuates inflammation after high-dose chemotherapy, but its relationship to oral mucositis after transplantation is undefined. We hypothesized that semaglutide would be associated with a lower risk of stomatitis and oral mucositis, without increased xerostomia, and with fewer systemic complications. Methods. Using the TriNetX federated network, adults aged 18–90 with stem-cell transplant status (ICD-10-CM Z94.84) were classified as semaglutide-exposed or unexposed. Outcomes were assessed from day 30 after the index event, with a prespecified 90-day analysis for oral mucositis. Primary endpoints were stomatitis (K12) and ulcerative oral mucositis (K12.3). Secondary endpoints included dry mouth, dysgeusia, systemic inflammation, and mortality. One—to—one propensity matching was used to balance age, sex, race/ethnicity, diabetes, and comorbidities. Results. After matching 1,355 pairs, stomatitis occurred in 4.0% versus 10.6% (risk ratio [RR] 0.378, 95% CI 0.262–0.545; hazard ratio [HR] 0.476, 95% CI 0.323-0.700; P<0.001). At 90 days, oral mucositis occurred in 2.43% versus 8.39% (RR 0.29, 95% CI 0.189-0.446; HR 0.278, 95% CI 0.179–0.431; P<0.0001). Dry mouth and taste/smell disturbances did not differ. Exposed patients had lower risks of sepsis-spectrum inflammation (6.2% versus 13.1%), influenza/pneumonia (11.6% versus 23.8%), and death (6.7% versus 25.0%). Conclusions. Semaglutide exposure was associated with lower coded oral mucositis, without increased xerostomia, and with concordant reductions in infectious and mortality outcomes. These findings warrant prospective confirmation and do not establish a preventive indication.