Is Jardiance (empagliflozin) contraindicated in a patient with a history of bladder cancer who is currently in remission and has no hematuria?

Is Bladder Cancer a Contraindication for Jardiance (Empagliflozin)?

No, bladder cancer—including a history of bladder cancer in remission—is not a contraindication for Jardiance (empagliflozin). Unlike pioglitazone, which carries specific warnings about bladder cancer risk, empagliflozin has no established causal relationship with bladder cancer and current evidence does not support restricting its use in patients with prior or active bladder malignancy.

Evidence-Based Rationale

Pioglitazone vs. Empagliflozin: Critical Distinction

• Pioglitazone is explicitly contraindicated in active bladder cancer and requires caution in patients with prior bladder cancer history, as stated in the 2025 American Diabetes Association guidelines 1
• Empagliflozin has no such restriction in current diabetes management guidelines, which do not list bladder cancer as a contraindication or precaution for SGLT2 inhibitors 1

Direct Safety Evidence for Empagliflozin

• A 2025 multi-country European post-authorization safety study of 151,055 matched patients found no increased risk of urinary tract cancers (adjusted HR = 0.88,95% CI: 0.66-1.17), bladder cancer specifically (adjusted HR = 0.91,95% CI: 0.63-1.33), or renal cancer (adjusted HR = 0.89,95% CI: 0.57-1.38) when comparing empagliflozin initiators to DPP-4 inhibitor initiators 2
• This represents the highest quality and most recent evidence directly addressing bladder cancer risk with empagliflozin, spanning multiple countries and robust propensity-score matching methodology 2

Mechanistic and Class Effect Considerations

• Early concerns about SGLT2 inhibitors and bladder cancer arose from dapagliflozin trials, where 9 of 5,936 dapagliflozin-treated patients developed bladder cancer versus 1 of 3,403 comparator patients 3
• However, all affected patients had typical bladder cancer risk factors (≥60-year-old males, 8 of 10 were current/former smokers), and 8 of 9 had microscopic hematuria prior to or within 6 months of treatment initiation, suggesting pre-existing undiagnosed disease rather than drug causation 3
• The totality of evidence does not suggest a causal relationship between SGLT2 inhibitors and bladder cancer 3

Clinical Application in Your Patient

For a patient with bladder cancer in remission and no hematuria:

• Empagliflozin can be safely initiated without specific bladder cancer-related restrictions 2
• The primary considerations should focus on standard SGLT2 inhibitor precautions: renal function (requires adequate eGFR), volume status, genital mycotic infection risk, and diabetic ketoacidosis risk 1
• Monitor for hematuria as part of routine diabetes care, but this is standard practice for all patients with diabetes regardless of medication choice, given the 80% presentation rate of bladder cancer with painless hematuria 4

Critical Monitoring Caveat

• If new hematuria develops during empagliflozin therapy, this mandates full urologic evaluation including cystoscopy and upper tract imaging, regardless of anticoagulation status or medication use 4
• This is not specific to empagliflozin—any adult with gross hematuria or unexplained microscopic hematuria requires complete evaluation to exclude recurrent malignancy 4
• Do not attribute new hematuria to empagliflozin's mechanism of action; assume bladder pathology until proven otherwise 4

Cardiovascular Benefit Consideration

• Empagliflozin demonstrated significant mortality reduction (5.7% vs. 8.3%, p < 0.001) in patients with type 2 diabetes and established cardiovascular disease, primarily through reduction in heart failure hospitalizations 5, 6
• This benefit appears independent of glycemic control and likely relates to the drug's diuretic effect 5
• In a patient with cardiovascular disease or heart failure risk, empagliflozin offers unique mortality benefits that should be weighed heavily in the treatment decision 6