13 May 2020 Sodium‐glucose Cotransporter 2 Inhibitors and the Risk for Urosepsis – A Multi‐site Prevalent New‐user Cohort Study
First published: 08 May 2020
Abstract
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.
Authors:
- Anat Fisher MD PhD
- Michael Fralick MD PhD
- Kristian B. Filion PhD
- Sophie Dell’Aniello MSc
- Antonios Douros MD PhD
- Éric Tremblay BPharm MSc
- Baiju R. Shah MD PhD
- Paul E. Ronksley PhD
- Silvia Alessi‐Severini PhD
- Nianping Hu PhD
- Shawn C. Bugden PharmD MSc
- Pierre Ernst MD MSc
- Lisa M. Lix PhD
- Canadian Network for Observational Drug Effect Studies (CNODES)
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