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SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS REDUCE SUICIDALITY, ALL-CAUSE MORTALITY, AND HOSPITALIZATION IN BIPOLAR DISORDER: A COHORT STUDY OF 1.23 MILLION ADULTS

Balwinder Singh — Raman Baweja2 1Mayo Clinic, 2Penn State College of Medicine

2026 ASCP Annual Meeting

Background

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated promising neuropsychiatric properties in animal research.

Aims

We aimed to examine whether SGLT2i exposure is associated with reduced incidence of suicidality, all-cause mortality, and hospitalization in bipolar disorder (BD).

Method

This cohort study utilized the TriNetX network (2008–2025) to identify 1,230,821 adults with BD, including 36,092 SGLT2i users and 1,194,729 non-users. The outcomes were incident suicidality, all-cause mortality, and hospitalization over 5-years of follow-up. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazards models, with additional 1:1 propensity score matching (PSM) for survival analysis conducted to control for confounding. Subgroup analyses stratified results by sex, race/ethnicity, concurrent mood stabilizer use, and somatic comorbidities.

Results

SGLT2i exposure was associated with significantly reduced risk of suicidality (aHR 0.75, 95% CI 0.71–0.79), all-cause mortality (aHR 0.55, 95% CI 0.52–0.57), and hospitalization (aHR 0.71, 95% CI 0.69–0.72). Protective associations remained consistent across subgroups, including patients receiving lithium, lamotrigine, or valproate. After PSM (31,001 matched pairs), five-year outcomes favored SGLT2i users: suicidality-free survival 94.51% versus 93.56%, overall survival 88.99% versus 79.57%, and hospitalization-free survival 72.39% versus 66.72% (all p < 0.001).

Conclusions

In this large cohort of over 1.2 million adults with BD, SGLT2i therapy was associated with substantially lower risks of suicidality, hospitalization, and all-cause mortality, with consistent benefits across demographic and clinical subgroups. These findings suggest SGLT2is may represent a promising therapeutic strategy to improve psychiatric and survival outcomes in BD. Prospective RCTs are warranted to evaluate long-term safety and efficacy.