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

Le Liu1,2, Chen Li1,2, Shuang Li3,2

  • 1Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Open Medicine (Warsaw, Poland)
|November 11, 2025
PubMed
Abstract

Insights

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are linked to increased risks for anxiety, obsessive-compulsive disorder, and bipolar disorder. This genetic study provides evidence for these SGLT2 inhibitor effects on mental health.

Area of Science:

  • Pharmacogenomics
  • Psychiatric Epidemiology
  • Metabolic Disorders

Background:

  • Observational studies suggest a link between SGLT2 inhibitors and psychiatric disorders.
  • The precise causal relationship remains unclear, necessitating further investigation.
  • SGLT2 inhibitors are commonly used for type 2 diabetes management.

Purpose of the Study:

  • To investigate the potential causal effects of SGLT2 inhibition on five major psychiatric disorders using Mendelian randomization.
  • To explore the relationship between SGLT2 inhibition and depression, anxiety, schizophrenia, OCD, and bipolar disorder.
  • To analyze the impact of glycated hemoglobin on psychiatric disorders.

Main Methods:

  • Mendelian randomization (MR) study design.
  • Utilized genetic variants from SLC5A2 gene and glycated hemoglobin data.
  • Employed MR and colocalization analyses, with type 2 diabetes as a positive control.

Main Results:

  • SGLT2 inhibition showed a significant association with increased risk for anxiety disorder, obsessive-compulsive disorder, and bipolar affective disorder.
  • No significant association was found between SGLT2 inhibition and schizophrenia.
  • The effect on depression did not meet statistical significance thresholds.

Conclusions:

  • This study provides genetic evidence supporting an increased risk of anxiety disorder, obsessive-compulsive disorder, and bipolar affective disorder with SGLT2 inhibitor use.
  • Findings highlight potential psychiatric risks associated with SGLT2 inhibitors.
  • Further research is warranted to elucidate the mechanisms underlying these associations.
Keywords:
SGLT2 inhibitoranxiety disorderdepressionobsessive-compulsive disorderpsychiatric disorder

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