Aims: The United States Food and Drug Administration has warned of an increased risk of serious urinary tract infection (UTI) and Fournier's gangrene in patients with diabetes mellitus type 2 treated with sodium-glucose cotransporter 2 inhibitors (SGLT2i). However, evidence on these risks is limited. We aimed to compare urosepsis rates in SGLT2i users with users of dipeptidyl peptidase-4 inhibitors (DPP4i) in a real-world setting.
Methods: We conducted a matched cohort study using a prevalent new-user design with time-conditional propensity scores. New users of SGLT2i from seven Canadian provinces and the United Kingdom were matched to DPP4i users. The primary outcome was hospitalization with a diagnosis of urosepsis, and the secondary outcome was Fournier's gangrene. Site-specific hazard ratios for urosepsis comparing SGLT2i with DPP4i were estimated using Cox proportional hazards models and pooled using a random-effects meta-analysis.
Results: We included 208 244 users of SGLT2i and 208 244 users of DPP4i. Among SGLT2i users, 42% initiated canagliflozin, 31% dapagliflozin, and 27% empagliflozin. During a mean follow-up of 0.9 years, patients initiating SGLT2i had a lower rate of urosepsis compared with those receiving DPP4i. The pooled adjusted hazard ratio was 0.58; 95% confidence interval (CI): 0.42-0.80. The incidence rates of Fournier's gangrene were numerically similar in SGLT2i (0.08 per 1000 person-years; 95% CI: 0.05-0.13) and DPP4i users (0.14; 95% CI: 0.09-0.21).
Conclusions: In this large multi-site study, we did not observe an increased risk for urosepsis associated with SGLT2i compared with DPP4i among patients with type 2 diabetes in a real-world setting.
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