Does empagliflozin (Jardiance) decrease serum lithium concentrations?

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Last updated: September 2, 2026 • View editorial policy

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Jardiance (Empagliflozin) DOES Lower Lithium Levels

Yes, Jardiance (empagliflozin) decreases serum lithium concentrations, and this interaction requires increased monitoring frequency of lithium levels during initiation and dose changes. 1

FDA-Confirmed Drug Interaction

The FDA drug label for Jardiance explicitly states that concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations 1. This is a documented class effect of SGLT2 inhibitors, not unique to empagliflozin.

Clinical Management Algorithm

When initiating Jardiance in patients on lithium:

  1. Obtain baseline lithium level before starting empagliflozin
  2. Monitor serum lithium concentrations more frequently during:
    • JARDIANCE initiation
    • Any dosage changes 1
  3. Anticipate need for lithium dose increases to maintain therapeutic levels
  4. Watch for loss of mood stabilization as lithium levels drop

Mechanism of Interaction

The mechanism involves increased renal excretion of lithium through SGLT2 inhibition 2. Empagliflozin blocks sodium-glucose reabsorption in the proximal convoluted tubules, which simultaneously:

  • Increases sodium delivery to distal nephron 1
  • Enhances lithium excretion (lithium shares sodium transport pathways)
  • Reduces lithium-glucose reabsorption in proximal tubules 2

This results in clinically significant decreases in serum lithium levels that are reproducible and not explained by other confounding factors 2.

Clinical Evidence

A documented case report demonstrated that empagliflozin caused reproducible and clinically significant decreases in serum lithium levels in a patient with schizoaffective disorder, requiring discontinuation of empagliflozin to maintain therapeutic lithium concentrations 2. The patient's lithium levels dropped to subtherapeutic ranges specifically when empagliflozin was present, despite stable renal function and no other medication changes.

Critical Pitfall to Avoid

Do not assume stable lithium levels will remain stable after starting Jardiance. The interaction is predictable and clinically meaningful. Failure to increase monitoring frequency risks:

  • Subtherapeutic lithium levels
  • Loss of bipolar disorder control
  • Psychiatric decompensation requiring hospitalization

Contrast With GLP-1 Agonists

Note that this interaction is opposite to what occurs with GLP-1 receptor agonists like semaglutide, which can increase lithium levels and cause toxicity 3. SGLT2 inhibitors and GLP-1 agonists have opposing effects on lithium clearance.

References

Related Questions

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.