A WIDELY used class of diabetes drugs may lower the dementia risk that shadows people with psychiatric disorders, a large US study suggests, hinting at a shared metabolic thread linking mental illness and neurodegeneration.
People with mood and psychotic disorders face a raised likelihood of developing dementia, yet treatment options to counter that danger are scarce. Researchers asked whether sodium-glucose cotransporter 2 (SGLT2) inhibitors, antidiabetic drugs with metabolic and mitochondrial effects, might reduce dementia risk in this high-risk group with psychiatric disorders.
Study Design and Patient Selection
The cohort study used a target trial emulation design and US Department of Veterans Affairs data from January 2016 to June 2024. Participants were aged 65 or older with major depressive disorder, bipolar disorder, or schizophrenia spectrum disorder, none having prior dementia or SGLT2 inhibitor use. The primary outcome was incident all-cause dementia; secondary outcomes were time to psychiatric emergency department (PED) visit and to psychiatric hospitalisation. Of 112,725 individuals (median age 74.1 years; 92.8% male; 49.3% with obesity), 7,631 (6.8%) were exposed to an SGLT2 inhibitor.
Reduced Dementia and Emergency Visits
In the intention-to-treat analysis, SGLT2 inhibitor use was associated with reduced odds of all-cause dementia (odds ratio 0.61; 95% CI 0.52 to 0.73) and of PED visits (OR 0.80; 95% CI 0.66 to 0.97), but not psychiatric hospitalisations (OR 0.68; 95% CI 0.44 to 1.04). In the per-protocol analysis, sustained use was linked to lower odds of dementia (OR 0.54; 95% CI 0.40 to 0.73) and psychiatric hospitalisations (OR 0.56; 95% CI 0.31 to 1.00), though not PED visits (OR 0.74; 95% CI 0.53 to 1.05).
Implications for High-Risk Patients
The authors concluded that, among older adults with mood and psychotic disorders, SGLT2 inhibitor use was associated with lower dementia risk and fewer psychiatric emergency visits, supporting a possible neuroprotective role. They argue the pattern strengthens the hypothesis of a shared metabolic vulnerability underlying psychiatric and neurodegenerative disease, positioning these drugs as candidate transdiagnostic treatments. Because the cohort was observational and overwhelmingly male, the authors called for further research before the findings could guide practice in patients with psychiatric disorders.
Reference
Liebers DT et al. Sodium-glucose cotransporter 2 inhibitors and dementia risk in patients with psychiatric disorders. JAMA Netw Open. 2026;9(6):e2619985.
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