Sodium–Glucose Cotransporter 2 Inhibitors and Risk of Bladde
The cohort included 89,799 new users of SGLT2 inhibitors (proportion of follow-up time by drug: dapagliflozin 59%, empagliflozin 40%, canagliflozin 0.8%, ertugliflozin <0.1%) and 65,200 new users of GLP-1 receptor agonists. After propensity score weighting, treatment groups were well-balanced on baseline characteristics (mean age 62 years, 64% men, 21–22% using insulin [data on file]). In the analyses of bladder cancer, 57,383 users of SGLT2 inhibitors and 49,398 users of GLP-1 receptor agonists remained at risk at 1 year after treatment initiation. The corresponding numbers in the analyses of renal cancer were 57,393 and 49,404. Median follow-up time was 2.3 years (interquartile range 1.6, 3.4) for SGLT2 inhibitors and 3.0 years (1.9, 4.2) for GLP-1 receptor agonists.

Use of SGLT2 inhibitors, as compared with GLP-1 receptor agonists, was not associated with a statistically significant increase in risk of bladder cancer (adjusted HR 0.88 [95% CI 0.59–1.31]) or renal cancer (adjusted HR 1.09 [95% CI 0.73–1.63]). In additional analyses, the adjusted HR did not increase with time since cohort entry. In several sensitivity analyses, including those with adjustment for additional variables such as smoking and glycated hemoglobin, the findings did not differ materially from those of the main analyses.

In this cohort study including almost 150,000 patients from nationwide registers in three countries, use of SGLT2 inhibitors was not associated with an increased risk of bladder cancer or renal cancer. The upper limits of the CIs were inconsistent with a relative risk increase of >31% for bladder cancer and 63% for renal cancer.