Is Jardiance (empagliflozin) contraindicated in a patient with polycystic kidney disease?

Jardiance is NOT Contraindicated in Polycystic Kidney Disease, But Current Guidelines Advise Against Its Use

Jardiance (empagliflozin) is not formally contraindicated in patients with polycystic kidney disease according to FDA labeling 1, but the 2025 KDIGO ADPKD guidelines explicitly state that SGLT2 inhibitors are "not advised at this time" due to lack of evidence 2, and the 2024 BMJ CKD guidelines exclude polycystic kidney disease patients from their SGLT2i recommendations 3.

The Evidence Landscape

Guideline Recommendations

The most recent and authoritative guidance comes from two major sources:

• 2025 KDIGO ADPKD Guidelines 2: Explicitly state that "use of sodium-glucose cotransporter-2 inhibitors is not advised at this time" for diabetes management in ADPKD patients due to lack of evidence. This is a clear recommendation against use, though not a formal contraindication.

• 2024 BMJ SGLT2i Guidelines 3: Specifically list "individuals with polycystic kidney disease" among groups where recommendations "may not be applicable" due to lack of representation in clinical trials.

FDA Labeling Position

The FDA label for Jardiance 1 lists only two contraindications:

• Hypersensitivity to empagliflozin
• Patients on dialysis

Polycystic kidney disease is NOT listed as a contraindication. However, the absence of a formal contraindication does not equate to safety or efficacy in this population.

Why the Concern?

The systematic exclusion of ADPKD patients from major SGLT2i trials stems from theoretical concerns:

1. Osmotic diuresis risk: SGLT2 inhibitors may provoke osmotic diuresis and activate vasopressin signaling, potentially accelerating cyst growth 4
2. Lack of safety data: ADPKD patients were excluded from pivotal trials like EMPA-KIDNEY 5 and DAPA-CKD
3. Uncertain effect on cyst progression: Whether SGLT2i accelerates or slows cyst growth remains unresolved

Emerging Evidence (Not Yet Practice-Changing)

Small observational and ongoing trial data suggest potential benefits, but these do NOT override current guideline recommendations:

• A 7-patient retrospective study 6 showed possible kidney function protection with dapagliflozin when combined with RAS inhibitors, but kidney volume increased in all patients
• The EMPA-PKD trial 7 is currently assessing safety but results are not yet available
• These studies are too small and preliminary to change practice 7, 6, 4

Clinical Decision Algorithm

For ADPKD patients requiring diabetes management:

1. First-line: Use metformin when eGFR ≥30 mL/min/1.73 m² 2
2. Second-line: Use GLP-1 receptor agonist when:
   • eGFR <30 mL/min/1.73 m²
   • Metformin not tolerated
   • Metformin alone insufficient for glycemic control 2
3. Avoid SGLT2 inhibitors until definitive safety and efficacy data become available

For ADPKD patients with heart failure or cardiovascular disease:

• The guidelines do not address this scenario directly
• Given the lack of safety data and explicit guideline recommendations against use, avoid SGLT2 inhibitors and use alternative heart failure therapies (ACE inhibitors, ARBs, beta-blockers, mineralocorticoid receptor antagonists)

Key Caveats

• If a patient is already on Jardiance when ADPKD is diagnosed, discuss discontinuation with nephrology consultation
• The distinction between "not advised" and "contraindicated" matters for liability and insurance, but clinically you should avoid prescribing it
• Future trial results may change this recommendation, but current evidence does not support use
• Genetic heterogeneity in ADPKD (PKD1, PKD2, DNAJB11, ALG8, ALG9) may affect response, but this remains speculative 4