Lower Risks of Incident Colorectal Cancer in SGLT2i Users Compared to DPP4i Users: A Propensity Score-matched Study with Competing Risk Analysis

Background Diabetes mellitus is associated with the development of colorectal cancer (CRC). There have been a lack of study comparing the risk of colorectal cancer in sodium-glucose co-transporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase 4 inhibitors (DPP4i), both of which commonly prescribed second line agents for diabetes. Methods We conducted a territory wide retrospective cohort study on patients with type 2 diabetes who was prescribed either of the two agents. Baseline demographics, use of other medications, comorbidities and biochemical parameters were extracted. Propensity score matching was performed to reduce the impacts of cofounders. Cause specific Cox regression was used to evaluate the risk of incident colorectal cancer in SGLT2i users, as compared to DPP4i users. Subgroup analyses based on age, gender and estimated glomerular filtration rate were performed. Results After propensity score matching, we included 13029 subjects who were prescribed SGLT2i and DPP4i respectively. Incidence rate ratio of CRC was 0.566 (0.418-0.766) in SGLT2i users. Overall, use of SGLT2i was associated with a lower risk of incident CRC (HR: 0.526; 95% CI: 0.382-0.724; P <0.001). In subgroup analyses, use of SGLT2i was associated with lower risks of incident CRC only in men (HR: 0.461; 95% CI: 0.303-0.702; P <0.001), patients < 65 years old and patients (HR:0.294; 95% CI: 0.174-0.496; P<0.001) with eGFR ≥ 45 mL/min/ 1.73m 2 (HR: 0.560; 95% CI: 0.395-0.792; P =0.001). Conclusion Use of SGLT2i may reduce risk of incident CRC as compared to use of DPP4i, especially in younger male patients with fairly preserved renal function.