Abstract
BACKGROUND: The role of sodium-glucose co-transporter 2 inhibitor (SGLT2i) drugs in the management of diabetes and cardiovascular disease is well-established, but emerging evidence suggests potential effects on cancer outcomes, including gastrointestinal (GI) cancers. We conducted an extensive, sex-oriented, real-world data analysis to investigate whether SGLT2i can enhance GI cancer outcomes when used alongside standard therapies such as chemotherapy and radiotherapy. METHODS: The study applied a retrospective cohort design with data from the TriNetX research database ( https://trinetx.com ), examining GI cancer patients treated with chemotherapy and/or radiotherapy between 2013 and 2023. The intervention cohort consisted of Gl cancer patients who received SGLT2i, while the control cohort did not. A 5-year follow-up period was used, and baseline characteristics were balanced using a 1:1 propensity score matching technique. Cox proportional-hazards and logistic regression models assessed mortality and morbidity risks between the cohorts. RESULTS: The study included 6,389 male and 3,457 female patients with GI cancer (ICD-10: C15-C25). The use of SGLT2i was significantly associated with improved survival for both male (HR 0.568; 95% CI 0.534-0.605) and female (HR 0.561; 95% CI 0.513-0.614) patients undergoing chemotherapy and/or radiotherapy. SGLT2i use also correlated significantly with lower hospitalisation rates both in male (OR 0.684; 95% CI 0.637-0.734) and female (OR, 0.590; 95% CI 0.536-0.650) patients. The analysis of GI cancer subtypes also demonstrated similar benefits, without significant adverse effects. CONCLUSIONS: Repurposing SGLT2 inhibitors for cancer treatment could potentially improve outcomes for GI cancer patients without causing significant side effects. Further clinical trials are needed to confirm these findings and establish the optimal condition for its application in GI cancer treatment.