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Sodium-Glucose Cotransporter 2 Inhibitors and Dementia Risk in Patients With Psychiatric Disorders

David T Liebers1,2, Tianshe He1,3, Rebecca A Betensky4

  • 1Department of Psychiatry, New York University (NYU) Grossman School of Medicine, New York.

JAMA Network Open
|June 30, 2026
PubMed
Abstract

Insights

Sodium-glucose cotransporter 2 (SGLT2) inhibitors may reduce dementia risk in individuals with psychiatric disorders. This study found SGLT2 inhibitor use was linked to lower dementia and psychiatric emergency department visit rates.

Area of Science:

  • Neuroscience
  • Psychiatry
  • Pharmacology

Background:

  • Individuals with mood and psychotic disorders face elevated dementia risk.
  • Sodium-glucose cotransporter 2 (SGLT2) inhibitors possess mitochondrial and metabolic properties suggesting potential neuroprotection.

Purpose of the Study:

  • To investigate the association between SGLT2 inhibitor treatment and the risk of incident dementia in patients with psychiatric disorders.
  • To evaluate the impact of SGLT2 inhibitors on other neuropsychiatric outcomes, including psychiatric emergency department visits and hospitalizations.

Main Methods:

  • A cohort study emulating a target trial using US Department of Veterans Affairs data (2016-2024).
  • Inclusion criteria: patients aged 65+ with major depressive disorder, bipolar disorder, or schizophrenia spectrum disorder, without prior dementia or SGLT2 inhibitor use.
  • Marginal structural models with inverse probability of treatment and censoring weighting were employed.

Main Results:

  • SGLT2 inhibitor use was associated with reduced odds of all-cause dementia (OR, 0.61; 95% CI, 0.52-0.73) in intention-to-treat analysis.
  • Sustained SGLT2 inhibitor use (per-protocol analysis) also showed lower odds of dementia (OR, 0.54; 95% CI, 0.40-0.73) and psychiatric hospitalizations (OR, 0.56; 95% CI, 0.31-1.00).
  • A significant reduction in psychiatric emergency department visits was observed (OR, 0.80; 95% CI, 0.66-0.97).

Conclusions:

  • SGLT2 inhibitor use is associated with a lower risk of dementia in older adults with mood and psychotic disorders.
  • Findings suggest a potential neuroprotective role for SGLT2 inhibitors in this high-risk psychiatric population.
  • Further research is warranted to confirm these neuroprotective effects.

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