Use of sodium-glucose cotransporter 2 inhibitors may beas associated with a lower likelihood of incident all-cause dementia among older patients with psychiatric disorders, according to a recent study.
Investigators conducted a retrospective cohort study using US Department of Veterans Affairs electronic health record data from January 1, 2016, to June 1, 2024. The analysis included patients aged 65 years or older with at least two diagnostic codes for major depressive disorder, bipolar disorder, or schizophrenia spectrum disorder and no prior dementia diagnosis or previous sodium-glucose cotransporter 2 (SGLT2) inhibitor use. Patients with diagnosed personality disorders were excluded.
The primary outcome was incident all-cause dementia, defined by two International Classification of Diseases, Ninth Revision codes for Alzheimer's disease, Alzheimer's disease–related dementias, or nonspecific dementias. Secondary outcomes included time to psychiatric emergency department utilization and time to psychiatric hospitalization.
The investigators used a target trial emulation design with 3-month periods and dynamic eligibility, allowing patients to enter once they met age and psychiatric diagnosis criteria. The patients also had to remain in the cohort for 6 months after meeting eligibility criteria to reduce potential reverse causation. Marginal structural models with inverse probability weighting were used to account for treatment and censoring.
The analysis included 112,725 patients, of whom 7,631 initiated SGLT2 inhibitor treatment. The cohort was predominantly male, and most patients had major depressive disorder. Overall, 4,616 patients developed dementia during follow-up.
In the intention-to-treat analysis, SGLT2 inhibitor initiation was associated with 39% lower odds of all-cause dementia and 20% lower odds of psychiatric emergency department visits compared with noninitiation. Psychiatric hospitalization was not statistically different in this analysis. In the per-protocol analysis, sustained SGLT2 inhibitor use was associated with a 46% lower odds of both all-cause dementia and psychiatric hospitalization but not psychiatric emergency department visits.
Estimated cumulative incidence analyses showed an absolute 5-year dementia risk of 1.6% among the patients who initiated SGLT2 inhibitors compared with 2.9% among noninitiators.
The investigators noted that residual confounding may remain despite adjustment, including confounding related to psychiatric disorder severity, baseline cognitive function, and diabetes indications. The use of diagnosis and prescription codes may have introduced misclassification, and psychiatric emergency department visits and hospitalizations were proxies for symptom severity. Generalizability may also be limited because the cohort was predominantly male and drawn from the Veterans Affairs health care system.
“Further investigation is warranted of SGLT2 inhibitors as potential transdiagnostic treatment options in [patients] with high-risk psychiatric disorders,” wrote lead study author David T. Liebers, MD, of the Department of Psychiatry at the New York University Grossman School of Medicine as well as the Clinical Research Division in the Nathan Kline Institute for Psychiatric Research, and colleagues.
The study was supported by grants from the National Institutes of Health and the Cooperative Studies Program of the Veterans Affairs Boston Healthcare System. Full disclosures can be found in the published study.
Source: JAMA Network Open
