SGLT2 Inhibitors Linked to Lower Dementia Risk in Older Adults With Psychiatric Disorders: JAMA
USA: Researchers have found in a target trial emulation study that the use of SGLT2 inhibitors was associated with a reduced risk of dementia among older adults with mood and psychotic disorders. An intention-to-treat analysis also demonstrated that SGLT2 inhibitor use was linked to fewer psychiatric emergency department visits.
The findings are particularly noteworthy because individuals with major depression, bipolar disorder, and schizophrenia are known to have an elevated risk of developing dementia but have historically been underrepresented in dementia prevention research. These results suggest that SGLT2 inhibitors may offer potential neuroprotective and psychiatric benefits beyond glycemic control, warranting further investigation into their role in dementia prevention among high-risk psychiatric populations.
The findings, published in JAMA Network Open, are from a study led by David T. Liebers of the Department of Psychiatry, New York University (NYU) Grossman School of Medicine, New York, and colleagues. The researchers investigated whether SGLT2 inhibitor use is associated with a lower risk of dementia and other neuropsychiatric outcomes in older adults with mood and psychotic disorders.
Using a target trial emulation design, the researchers analyzed data from 112,725 adults aged 65 years or older with major depressive disorder, bipolar disorder, or schizophrenia spectrum disorder in the US Department of Veterans Affairs healthcare system (2016–2024). Participants had no prior dementia diagnosis or SGLT2 inhibitor use.
The primary outcome was incident all-cause dementia, while psychiatric emergency department visits and hospitalizations were evaluated as secondary outcomes using both intention-to-treat and per-protocol analyses.
Key findings of the study include:
- The study included 112,725 older adults, of whom 7,631 (6.8%) initiated SGLT2 inhibitor therapy.
- In the intention-to-treat analysis, SGLT2 inhibitor use was associated with a 39% lower risk of all-cause dementia (OR 0.61).
- SGLT2 inhibitor use was also associated with a 20% lower risk of psychiatric emergency department visits in the intention-to-treat analysis (OR 0.80).
- No statistically significant reduction in psychiatric hospitalizations was observed in the intention-to-treat analysis.
- In the per-protocol analysis, sustained SGLT2 inhibitor use for at least three months was associated with a 46% lower risk of all-cause dementia (OR 0.54).
- Sustained SGLT2 inhibitor use was also associated with lower odds of psychiatric hospitalization (OR 0.56), although no significant reduction in psychiatric emergency department visits was observed in this analysis.
The findings suggest that SGLT2 inhibitors may offer benefits beyond glycemic control by targeting shared metabolic mechanisms underlying psychiatric and neurodegenerative disorders. Their use was associated with a lower risk of dementia and psychiatric emergency department visits in older adults with mood and psychotic disorders.
The researchers acknowledged limitations including potential residual confounding, reliance on diagnostic and prescription codes, the predominantly male veteran population limiting generalizability, and underpowered subgroup analyses that require further investigation.
The researchers concluded that SGLT2 inhibitor use was associated with a reduced risk of all-cause dementia and psychiatric emergency department visits, supporting further studies to evaluate their potential neuroprotective role in high-risk psychiatric populations.
Reference:
Liebers DT, He T, Betensky RA, et al. Sodium-Glucose Cotransporter 2 Inhibitors and Dementia Risk in Patients With Psychiatric Disorders. JAMA Netw Open. 2026;9(6):e2619985. doi:10.1001/jamanetworkopen.2026.19985
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