Comparisons of the risks of new-onset prostate cancer in type 2 diabetes mellitus between SGLT2I and DPP4I users: A population-based cohort study

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2I) have been suggested to reduce new-onset cancer amongst type-2 diabetes mellitus (T2DM) patients. This study aims to compare the risks of prostate cancer between SGLT2I and dipeptidyl peptidase-4 inhibitors (DPP4I) amongst T2DM patients.

Design, setting and participants: This was a retrospective population-based cohort study of prospectively recorded data on male patients with T2DM who were prescribed either SGLT2I or DPP4I between 1st January 2015 and 31st December 2020 from Hong Kong.

Methods: The primary outcome was new-onset prostate cancer. The secondary outcomes included cancer-related mortality and all-cause mortality. Propensity score matching (1:1 ratio) using the nearest neighbor search was performed and multivariable Cox regression was applied. A three-arm analysis including the glucagon-like peptide-1 receptor agonist (GLP1a) cohort was conducted.

Results: This study included 42129 male T2DM patients (median age: 61.0 years old [SD: 12.2]; SGLT2I: n = 17,120; DPP4I: n = 25,009). In the propensity score matched cohort, the number of prostate cancers was significantly lower in SGLT2I users (n = 60) than in DPP4I (n = 102). Over a follow-up duration of 5.61 years, SGLT2I was associated with lower prostate cancer risks (HR: 0.45; 95% CI: 0.30-0.70) than DPP4I after adjustments. The subgroup analyses showed that the interactions between SGLT2I and age, hypertension, heart failure, and GLP-1a were not statistically significant. The result remained consistent in the sensitivity analysis.

Conclusion: The study demonstrated SGLT2I was associated with lower risks of new-onset prostate cancer after propensity score matching and adjustments compared to DPP4I amongst T2DM patients.