S1594 Association Between SGLT2 Inhibitor Use and Inflammatory Bowel Disease in Non-Diabetic Patients

Introduction: Sodium–glucose cotransporter-2 inhibitors (SGLT2is) are now standard treatments for chronic kidney disease (CKD) and heart failure (HF), including in patients without diabetes. In addition to lowering blood glucose, SGLT2is possess anti-inflammatory and antioxidative properties, which may contribute to their benefits in CKD and HF. Although early studies have suggested a potential protective effect of SGLT2is against Crohn’s disease in patients with type 2 diabetes, their role in preventing inflammatory bowel disease (IBD) and related complications in non-diabetic patients with CKD or HF remains unclear. This study aimed to assess whether SGLT2i use is associated with a reduced risk of IBD and its complications in this population. Methods: We conducted a retrospective cohort study using TriNetX, a network of de-identified EHRs from inpatient and outpatient settings. Adults with CKD or HF diagnosed in the past 5 years were identified via International Classification of Diseases-10 codes. Patients with diabetes or prior IBD were excluded. The exposure group included those prescribed SGLT2is; controls had no SGLT2i use. Propensity score matching (1:1) was done using age, sex, race, ethnicity, obesity, smoking, transplant history, abdominal surgery, and selected medications (GLP-1 agonists, DPP-4 inhibitors, ACE inhibitors, ARBs, beta-blockers, spironolactone). We assessed incidence of different type of UC and CD, reported as ORs with 95% CIs. Results: After 1:1 propensity score matching, each cohort included 119,250 non-diabetic patients with CKD or HF. SGLT2i users showed significantly lower odds of developing ulcerative colitis (UC) (OR 0.62; 95% CI, 0.54–0.70) and Crohn’s disease (CD) (OR 0.74; 95% CI, 0.62–0.88) compared to controls. Subtype analysis revealed reduced odds for ulcerative pancolitis (OR 0.54; 95% CI, 0.40–0.72), ulcerative proctitis (OR 0.56; 95% CI, 0.36–0.87), left-sided colitis (OR 0.41; 95% CI, 0.21–0.77), CD of the large intestine (OR 0.66; 95% CI, 0.47–0.92), and CD involving both small and large intestines (OR 0.61; 95% CI, 0.40–0.94). Conclusion: In this large, propensity-matched cohort of non-diabetic patients with CKD or HF, SGLT2i use was associated with a significantly reduced risk of developing ulcerative colitis or Crohn’s disease. These findings suggest a potential gastrointestinal protective effect of SGLT2 inhibitors and further studies are needed to validate these results and further investigate the underlying mechanisms.