SGLT2 inhibitors tied to lower dementia risk in psychiatric patients

Clinical takeaway: For older adults with major depression, bipolar disorder, or schizophrenia spectrum disorder, SGLT2 inhibitors may offer benefits beyond cardiometabolic disease, with this study linking their use to lower dementia risk and fewer psychiatric emergency department visits.

Older adults with mood and psychotic disorders are at increased risk for dementia. In a large Veterans Affairs (VA) cohort study, SGLT2 inhibitor use was associated with lower risks of dementia and psychiatric emergency visits, adding to growing evidence that metabolic pathways may contribute to both psychiatric illness and neurodegeneration.

The study included 112,725 adults aged 65 years or older with major depressive disorder, bipolar disorder, or schizophrenia spectrum disorder and no prior dementia diagnosis. The predominantly male cohort reflected the VA population.

SGLT2 inhibitor initiation was associated with a 39% lower relative odds of incident all-cause dementia. Over five years, the estimated absolute dementia risk was 1.6% among SGLT2 inhibitor users versus 2.9% among nonusers. Sustained treatment was associated with an even stronger reduction.

The association extended beyond cognition. SGLT2 inhibitor initiation was associated with fewer psychiatric emergency department visits, while sustained use was also linked to fewer psychiatric hospitalizations, suggesting broader neuropsychiatric benefits.

For patients who already meet established indications for an SGLT2 inhibitor, this study provides another factor to consider when selecting therapy and discussing its potential benefits.

The results also support the concept that psychiatric illness and dementia may share metabolic mechanisms, including impaired insulin signaling, mitochondrial dysfunction, and inflammation. These biologic links provide a rationale for future studies evaluating whether SGLT2 inhibitors have direct neuroprotective effects.

"These findings support the hypothesis of shared metabolic vulnerability across psychiatric and neurodegenerative diseases. Further investigation is warranted of SGLT2 inhibitors as potential transdiagnostic treatment options in individuals with high-risk psychiatric disorders," the study authors concluded.

Source: Liebers DT, et al. (2026 June 30) JAMA Netw Open. Sodium-glucose cotransporter 2 inhibitors and dementia risk in patients with psychiatric disorders