Association of SGLT2 inhibition with psychiatric disorders: A Mendelian randomization study.

BACKGROUND

Some observational studies have reported that sodium-glucose cotransporter 2 (SGLT2) inhibitors may have an impact on psychiatric disorders. This Mendelian randomization (MR) study aims to explore the causal relationship between SGLT2 inhibition and five types of psychiatric disorders.

METHODS

Genetic variants associated with the SLC5A2 gene and glycated hemoglobin were selected from the eQTLGen Consortium and Genotype-Tissue Expression datasets. Type 2 diabetes served as a positive control in the application of MR and colocalization analyses to investigate potential causal relationships between SGLT2 inhibition and depression, anxiety disorder, schizophrenia, obsessive-compulsive disorder, and bipolar affective disorder. The impact of glycated hemoglobin on psychiatric disorders was additionally analyzed.

RESULTS

SGLT2 inhibition was associated with an increased risk of anxiety disorder, obsessive-compulsive disorder, and bipolar affective disorder. The effect of SGLT2 inhibition on depression did not reach Bonferroni-corrected significance levels. No association was found between SGLT2 inhibition and schizophrenia.

CONCLUSIONS

This study provides genetic evidence supporting that SGLT2 inhibitors increase the risk of obsessive-compulsive disorder, anxiety disorder, and bipolar affective disorder.