Trial results for the study "Empa PASS on Urinary Tract Malignancies" (NCT03464045) investigating empagliflozin in patients with Type 2 Diabetes Mellitus were posted on ClinicalTrials.gov on 2025-03-28. The study aimed to assess the risk of urinary tract malignancies compared to dipeptidyl peptidase-4 (DPP-4) inhibitors. Overall, the crude Hazard Ratio for urinary tract cancer was 0.8 (95% CI: 0.61 to 1.06) for empagliflozin initiators versus DPP-4 inhibitor initiators.
Background
The study, titled "Empa PASS on Urinary Tract Malignancies," aimed to assess the risk of urinary tract malignancies in patients initiating empagliflozin (free or fixed dose combination) compared to patients initiating a dipeptidyl peptidase-4 (DPP-4) inhibitor. This investigation was conducted in patients with Type 2 Diabetes Mellitus.
Trial design
The study (NCT03464045) was a completed observational study that enrolled 344,995 participants with Type 2 Diabetes Mellitus. The study compared the safety profile of patients initiating empagliflozin with those initiating DPP-4 inhibitors, specifically focusing on the occurrence of urinary tract malignancies.
Key results
The study evaluated the occurrence of urinary tract cancer and bladder cancer in patients initiating empagliflozin compared to DPP-4 inhibitors across multiple countries. For the overall cohort (PS-matched across all countries), the event rate for urinary tract cancer was 1.10 Events per 1000 patient years for empagliflozin initiators, compared to 1.29 Events per 1000 patient years for DPP-4 inhibitor initiators. Country-specific rates generally followed this trend; for instance, in the UK, empagliflozin initiators had 0.73 Events per 1000 patient years for urinary tract cancer versus 1.07 Events per 1000 patient years for DPP-4 inhibitor initiators.
For bladder cancer, in the UK, empagliflozin initiators had 0.45 Events per 1000 patient years, compared to 0.67 Events per 1000 patient years for DPP-4 inhibitor initiators. In Sweden, these rates were 0.92 Events per 1000 patient years and 1.03 Events per 1000 patient years, respectively.
Key analyses for the risk of urinary tract cancer showed:
- Crude Hazard Ratio (HR): 0.8 (95.0% CI: 0.61 to 1.06), with a p-value of 0.122.
- Base HR (adjusted for unbalanced variables): 0.89 (95.0% CI: 0.67 to 1.18), with a p-value of 0.417.
- Adjusted HR (adjusted for unbalanced and time-varying covariates): 0.88 (95.0% CI: 0.66 to 1.17), with a p-value of 0.376.
For the risk of bladder cancer, analyses showed:
- Crude Hazard Ratio (HR): 0.79 (95.0% CI: 0.55 to 1.15), with a p-value of 0.22.
- Base HR (adjusted for unbalanced variables): 0.91 (95.0% CI: 0.63 to 1.32), with a p-value of 0.628.
- Adjusted HR (adjusted for unbalanced and time-varying covariates): 0.91 (95.0% CI: 0.63 to 1.33), with a p-value of 0.632.
What this means
The results of this large observational study suggest that empagliflozin may be associated with a numerically lower risk of urinary tract malignancies, including bladder cancer, compared to DPP-4 inhibitors in patients with Type 2 Diabetes Mellitus. While the Hazard Ratios consistently fell below 1.0, indicating a potentially reduced risk, the p-values for these analyses were not statistically significant. These findings contribute to the long-term safety profile assessment of empagliflozin regarding urinary tract cancer risk.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03464045, titled "Empa PASS on Urinary Tract Malignancies," were posted on 2025-03-28 on clinicaltrials.gov.