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.

Objective: To assess long-term systemic complications and mortality risk associated with oral mucositis (OM) in breast cancer patients treated with monoclonal antibody-drug conjugates (mADCs). Materials and Methods: Retrospective cohort study using TriNetX federated data from 88 healthcare organizations. Adult breast cancer patients receiving mADCs with (n=1,784) or without (n=61,616) OM (ICD-10 K12.31) were 1:1 propensity score-matched on race, morbidity-related factors, ECOG status, and BMI (1,784 per cohort). Outcomes, volume depletion, fluid/electrolyte disorders, respiratory and circulatory disease, malaise/fatigue, pain, dysphagia, and mortality were assessed from 1-day post-index using risk differences, Kaplan-Meier estimates, and Cox hazard ratios. Results: Mucositis patients had significantly higher risks of fluid/electrolyte disorders (39.1% vs 32.1%; HR 0.753), respiratory disease (48.5% vs 39.0%; HR 0.697), circulatory disease (63.7% vs 51.2%; HR 0.667), pain (16.1% vs 11.7%; HR 0.664), dysphagia (10.4% vs 8.2%; HR 0.702), and mortality (26.1% vs 19.3%; HR 0.670; all P< 0.001). Volume depletion and malaise/fatigue showed attenuated absolute risk differences but persistent survival differences (HR 0.824 and 0.855). Recurrent event counts did not differ. Conclusions: OM in mADC-treated breast cancer patients predicts greater long-term systemic morbidity and mortality, despite confounder balancing. Clinical Relevance: OM may serve as a sentinel marker, identifying patients at elevated risk of systemic decline and warranting closer post-therapy surveillance rather than treatment as an isolated, self-limited toxicity. These findings support incorporating oral health assessment into oncologic risk stratification and encourage interdisciplinary oncology-dentistry collaboration for early mucositis prevention and management, which may help reduce downstream systemic morbidity and improve survival.

Background/Objectives: Oral mucositis (OM) is a recognized toxicity of antibody–drug conjugates (ADCs), but its long-term systemic implications are unknown. We assessed long-term systemic complications and mortality associated with OM in patients with breast cancer treated with monoclonal antibodies and antibody–drug conjugates (mADCs). Materials and Methods: This retrospective cohort study used TriNetX data from 88 healthcare organizations. Adults with breast cancer receiving mADCs with (n = 1784) or without (n = 61,616) OM (ICD-10-CM K12.31) were 1:1 propensity score-matched on race, external causes of morbidity, ECOG performance status, and body mass index (1784 per cohort). Outcomes included volume depletion, fluid/electrolyte disorders, respiratory and circulatory disease, malaise/fatigue, pain, dysphagia, and all-cause mortality, assessed from 1 day after the index event using risk differences, Kaplan–Meier analysis, and Cox hazard ratios (HRs). Results: Patients with OM had higher risks of fluid/electrolyte disorders (39.1% vs. 32.1%), respiratory disease (48.5% vs. 39.0%), circulatory disease (63.7% vs. 51.2%), pain (16.1% vs. 11.7%), dysphagia (10.4% vs. 8.2%), and mortality (26.1% vs. 19.3%), with HRs (no OM vs. OM) of 0.664–0.753 (log-rank p ≤ 0.002 for all). Volume depletion and malaise/fatigue showed no significant absolute risk differences but significant survival differences (HR 0.824 and 0.855). Recurrent event counts did not differ. Conclusions: In patients with breast cancer treated with mADCs, OM was associated with greater long-term systemic morbidity and mortality after propensity score matching. OM may serve as a marker of systemic vulnerability, supporting routine oral health assessment and oncology–dentistry collaboration during ADC therapy, with implications for toxicity management as ADC use expands.

Background: Oral mucositis is a major toxicity of hematopoietic stem-cell transplantation (HSCT). In preclinical models, glucagon-like peptide-1 (GLP-1) signaling promotes intestinal epithelial repair after chemotherapy-induced injury, 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 COVID-19 Research Network (88 healthcare organizations; query executed 13 August 2026), adults aged 18–90 with stem-cell transplant status (ICD-10-CM Z94.84) were classified as semaglutide-exposed or unexposed. The index date was the first date on which all cohort-defining criteria were met; because Z94.84 is a status code, the index date does not correspond to the date of transplantation. Long-term outcomes were assessed from day 30 after the index date until the end of available records; oral mucositis was assessed as a 3-month outcome (days 1–90 after the index date) in a separate propensity-matched analysis that additionally balanced underlying hematologic diagnoses. The primary endpoint was stomatitis and related lesions (K12); oral mucositis (K12.3, a subcategory of K12) was the key secondary endpoint. Dry mouth, taste/smell disturbances, candidal stomatitis, food and fluid intake codes, systemic inflammation, influenza/pneumonia, graft-versus-host disease, and mortality were exploratory endpoints. One-to-one propensity-score matching was used to balance age, sex, race/ethnicity, type 2 diabetes, external causes of morbidity, body-mass index, and Eastern Cooperative Oncology Group (ECOG) performance status. Results: During long-term follow-up (1355 matched 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 3 months (1152 matched pairs), oral mucositis occurred in 2.7% versus 9.6% (RR 0.280, 95% CI 0.178–0.442; risk difference −6.9 percentage points; p < 0.001; the proportional-hazards assumption was not met, so the hazard ratio is reported only as an average effect). Dry mouth and taste/smell disturbances did not differ. In exploratory analyses, exposed patients had lower observed risks of sepsis-spectrum inflammation (6.2% versus 13.1%), influenza/pneumonia (11.6% versus 23.8%), and death (6.7% versus 25.0%), although follow-up was considerably shorter in the exposed cohort. Conclusions: Among patients with a documented history of HSCT, semaglutide exposure was inversely associated with ICD-coded stomatitis and oral mucositis, without a detectable increase in coded xerostomia, and with lower observed risks of infectious outcomes and death. Because the timing of exposure relative to transplantation could not be determined and residual confounding is likely, these findings are hypothesis-generating, require prospective confirmation, and do not establish a preventive indication.