Empagliflozin Not Linked to Urinary Tract Cancer in T2D

TOPLINE:

Adults with type 2 diabetes (T2D) who initiated empagliflozin treatment did not face a higher risk for urinary tract cancers (UTCs), such as bladder or renal cancer, than those who initiated DPP-4 inhibitors, supporting the removal of UTC from the safety specifications of the empagliflozin risk-management plan.

METHODOLOGY:

• Empagliflozin — an SGLT2 inhibitor — was approved by the EU in 2014 to improve blood glucose control in adults with T2D; however, early toxicology data and clinical cases with a related drug suggested a possible risk for UTC.
• Researchers conducted a non-interventional, cohort-based post-authorisation safety study using linked databases and registers in the United Kingdom, Sweden, and Finland to compare the risk for UTC between adults with T2D who initiated empagliflozin and those who initiated DPP-4 inhibitors.
• They analysed 151,055 adults with T2D (mean age, 57-63 years; 58.4%-67.8% women), of whom 55,378 were empagliflozin initiators who were matched with 95,677 DPP-4 inhibitor initiators using a propensity score-matching analysis.
• The follow-up started after treatment initiation and ranged from 599 to 656 days for empagliflozin users and 582 to 681 days for DPP-4 inhibitor users.
• The primary outcome was the occurrence of UTC, with separate assessments for bladder cancer and renal cancer; the observation period for cancer outcomes began 180 days (latency period) after treatment initiation.

TAKEAWAY:

• A meta-analysis of country-level estimates showed no increased risk for UTCs among empagliflozin initiators vs DPP-4 inhibitor initiators (adjusted hazard ratio [aHR], 0.88; 95% CI, 0.66-1.17).
• Similarly, the analysis of specific UTCs showed no elevated risk for bladder cancer (aHR, 0.91; 95% CI, 0.63-1.33) or renal cancer (aHR, 0.89; 95% CI, 0.57-1.38) among empagliflozin users vs DPP-4 inhibitor users.
• Sensitivity analyses with an extended grace period (treatment interruption), an extended latency period, and an extended delay of treatment discontinuation time found no increased risk for UTC among empagliflozin users vs DPP-4 inhibitor users.

IN PRACTICE:

“This study reinforces previous evidence that empagliflozin use is not associated with an increased risk of urinary tract malignancies compared with DPP-4i [DPP-4 inhibitor] use,” the authors wrote.

SOURCE:

This study was led by Niklas Schmedt, PhD, Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany. It was published online on June 13, 2025, in Diabetes, Obesity and Metabolism.

LIMITATIONS:

The observational design of the study introduced unmeasured residual baseline confounding, time-dependent confounding, and selection bias. The actual use of medications, particularly the oral ones, by the participants could not be verified with certainty.

DISCLOSURES:

This study was supported by Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance. Five authors reported being employees of IQVIA under contract with Boehringer Ingelheim to conduct the study. Two authors reported being employees of Boehringer Ingelheim.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.