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Sodium-Glucose Cotransporter 2 Inhibitors for Lithium-Associated Kidney Dysfunction in Mood Disorders: A Real-World

Mete Ercis1, Idil Tarikogullari1, Vanessa K Pazdernik2

  • 1Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN, USA.

Medrxiv : the Preprint Server for Health Sciences
|September 15, 2025
PubMed
Abstract

Insights

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improved kidney function in patients with mood disorders on lithium. This suggests SGLT2i may help prevent lithium-induced kidney damage.

Area of Science:

  • Nephrology
  • Psychiatry
  • Pharmacology

Background:

  • Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are used for type 2 diabetes and show renal benefits.
  • The impact of SGLT2i on lithium-associated kidney dysfunction is unknown.

Purpose of the Study:

  • To investigate the effect of SGLT2i on estimated glomerular filtration rate (eGFR) in patients with mood disorders receiving long-term lithium therapy.

Main Methods:

  • Historical cohort study at Mayo Clinic (2001-2023).
  • Included patients with mood disorders on lithium (≥6 months) and SGLT2i (≥1 month).
  • Analyzed eGFR trajectories using linear mixed-effects models before and after SGLT2i initiation.

Main Results:

  • Fifty-six patients were included (mean age 57.4 years).
  • Before SGLT2i, eGFR declined by -1.43 mL/min/1.73 m²/year.
  • After SGLT2i initiation, eGFR increased by 0.69 mL/min/1.73 m²/year (p=0.025).

Conclusions:

  • SGLT2i treatment was associated with improved eGFR trajectory in patients on long-term lithium.
  • SGLT2i may mitigate lithium-associated kidney dysfunction.
  • Randomized controlled trials are needed to confirm these findings.
Keywords:
Bipolar DisorderCreatinineKidneyLithiumMood DisordersSodium-Glucose Transporter 2 Inhibitors

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