Unmasking the clinical impact of SGLT-2 inhibitors in stage IV colorectal cancer: A real-world multicenter analysis.

e15628 Background: Colorectal cancer (CRC) is the fourth most diagnosed cancer in the United States, and stage IV CRC has a 5-year survival rate of 11%–14%. One risk factor for the development of CRC is Diabetes Mellitus (DM). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are associated with improved survival in patients with CRC and DM, but their impact in stage IV CRC remains unclear. This study explores the effects of SGLT2i on mortality, ICU admissions, and other clinical outcomes in diabetic patients diagnosed with stage IV CRC. Methods: We performed retrospective analysis using deidentified, aggregate patient data from the TriNetX research network. Patients aged 18-75 with stage IV CRC and DM were sorted into two cohorts: those prescribed SGLT2i after being diagnosed with DM and stage IV CRC vs. those with no SGLT2i use. Patients were then 1:1 propensity matched on variables such as demographics, comorbidities, procedures, exposure to other diabetic medications, and systemic therapies for CRC. Following matching, there were 1614 patients in each cohort. Multivariable logistic regression analysis was performed to define adjusted Odds ratios (OR) with 95% confidence intervals. Results: SGLT2i exposure demonstrated improved clinical outcomes. There was a reduction in all-cause mortality (OR 0.359, 95% CI 0.306–0.421) and ICU admissions (OR 0.750, 95% CI 0.593–0.947). These patients also exhibited reduced rates of thromboembolic events (OR 0.575, 95% CI 0.438-0.755), bowel obstruction (OR 0.510, 95% CI 0.375-0.695), and gastrointestinal bleeding (GIB) (OR 0.600, 95% CI 0.452-0.796), as well as a decreased need for blood transfusions (OR 0.410, 95% CI 0.293-0.573). However, there was no significant effect on major adverse cardiac events (OR 1.125, 0.798-1.587) or rates of biliary obstruction/cholangitis (OR 0.850, 95% CI 0.523-1.381). Conclusions: DM and Stage IV CRC patients who were prescribed SGLT2i were found to have lower rates of all-cause mortality, ICU admissions, thromboembolic events, bowel obstruction, GIB, and blood transfusion requirements. These findings suggest SGLT2i may provide benefits that aid in reducing systemic and treatment-limiting complications in this high-risk population. Further investigation is required to determine if SGLT2i may serve a role in adjunctive therapy to maximize patient outcomes and enhance the overall care of stage IV CRC patients. Effects of SGLT2i in patients with Stage IV CRC and DM. Outcome Odds ratio (95% CI) P value All-cause mortality 0.359 (0.306–0.421) <0.001 Blood transfusion 0.410 (0.293–0.573) <0.001 ICU admission 0.750 (0.593–0.947) 0.015 Thromboembolic events 0.575 (0.438–0.755) <0.001 Major adverse cardiac events (MACE) 1.125 (0.798–1.587) 0.501 Bowel obstruction 0.510 (0.375–0.695) <0.001 GI bleed 0.600 (0.452–0.796) <0.001 Biliary obstruction/cholangitis 0.850 (0.523–1.381) 0.511