New-onset prostate cancer in type 2 diabetes mellitus exposed to the SGLT2I, DPP4I and GLP1a: 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. Objective This real-world 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 type-2 diabetes mellitus (T2DM) male patients prescribed either SGLT2I or DPP4I between January 1 st 2015 and December 31 st 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 neighbour search was performed and multivariable Cox regression was applied to compare the risk. A three-arm sensitivity 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=17120; DPP4I: n=25009). After matching, the number of prostate cancers was significantly lower in SGLT2I users (n = 60) than in DPP4I (n = 102). SGLT2I use was associated with lower prostate cancer risks (HR: 0.45; 95% CI: 0.30-0.70) after adjustments than DPP4I. The results remained consistent in the sensitivity analysis. SGLT2I reduced the risks of prostate cancer prominently amongst patients who were older (age >65), patients with 2 nd and 3 rd quartile of HbA1c, concurrent metformin uses, and concurrent sulphonylurea uses. SGLT2I was associated with higher risks of prostate cancer amongst sulphonylurea non-users. Conclusion The real-world study demonstrated SGLT2I was associated with lower risks of new-onset prostate cancer after matching and adjustments compared to DPP4I. This result warrants further prospective studies. Graphical abstract