Impact of SGLT2i and GLP1 agonists on prostate cancer incidence and outcomes: A real-world propensity score–matched cohort study.

e17148 Background: Prior studies have shown a decreased incidence of PCa in males with type two diabetes mellitus (TIIDM) receiving GLP1 agonists (GLP1-RA’s) as well as those receiving SGLT2 inhibitors (SGLT2i’s). To our knowledge, no studies have compared the incidence of PCa between these two classes of medications in males with TIIDM. Further, our study aims to compare their impact on PCa-specific outcomes. Methods: We utilized TriNetX’s US Collaborative Network. Males aged 18 to 90 with TIIDM were divided into three cohorts: those receiving SGLT2i’s, those receiving GLP1-RA’s, and those receiving neither. Patients with type one diabetes mellitus were excluded from all cohorts. Cohorts were propensity score-matched based on age, sex, race, social determinants of health, other hypoglycemic medications, endocrine disorders, genitourinary disorders, BMI, BPH, and BRCA1/2 mutation status. Using ICD-10 codes, we evaluated the following outcomes: mean PSA levels, PCa incidence, Gleason scores 7-10, and presence of osseous metastases. Generalized linear models were used to measure the association, and estimates were presented as mean values and odds ratios with 95% confidence intervals. Results: After matching, cohorts consisted of 309,556, 237,965, and 237,238 patients, respectively. Mean ages varied between 58.4 – 64.1 years of age. Caucasians accounted for 66.3-70.5% and black or African American for 13.9-15.1% of patients. Compared to controls, patients receiving SGLT2i had a statistically lower risk of developing PCa (OR 0.842, 95% CI 0.809 - 0.876, p < 0.0001). The SGLT2i. cohort had a significantly lower risk of developing PCa compared to the GLP1-RA cohort (OR 0.823, 95% CI 0.786-0.863, p < 0.0001). There was no difference in PCa incidence between the GLP1-RA cohort and control group (OR 1.024, 95% CI 0.978 - 1.072, p = 0.3071). Mean PSA scores were significantly lower in the SGLT2i group compared to control (4.10 vs 5.99, p = 0.0003) and the GLP1-RA group compared to control (3.203 vs. 4.206, p = 0.0066). There was a significantly lower risk of Gleason score 7 in the SGLT2i group vs. the GLP1-RA group (OR 0.618, 95% CI 0.43-0.89, p = 0.0089). The risk of osseous metastasis was also significantly lower in the SGLT2i group compared to control (OR 0.794, 95% CI 0.743-0.849, p < 0.0001), the GLP1-RA group compared to control (OR 0.763, 95% CI 0.703-0.828, p < 0.0001), and in the SGLT2i. group compared to the GLP1-RA group (OR 1.099, 95% CI 1.01-1.196, p = 0.0279). Conclusions: Overall, our data indicate that SGLT2i's may lower mean PSA levels, as well as the risk of PCa and osseous metastases in males with TIIDM compared to matched controls. Further, SGLT2i's appear to have superior effect on these outcomes compared to GLP1-RA's. GLP1-RA's may reduce mean PSA scores and osseous metastasis risk compared to matched-controls. However, more prospective studies are needed to confirm these findings.