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Updated: Apr 9, 2026

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Sodium-glucose cotransporter 2 inhibitors and constipation: a two-sample mendelian randomization study

Qiuhui Liu1, Jing Ning2, Zihan Chen2

  • 1Department of Preventive Treatment of Disease, Wujin Hospital of Traditional Chinese Medicine, Wujin TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Changzhou, China.

Frontiers in Pharmacology
|April 8, 2026
PubMed
Abstract

Insights

Sodium-glucose cotransporter 2 (SGLT-2) inhibition may reduce constipation risk. A specific metabolite, DSGEGDFXAEGGGVR, appears to mediate this protective effect, offering new insights for constipation management.

Area of Science:

  • Pharmacology
  • Metabolomics
  • Gastroenterology

Background:

  • Conflicting evidence exists on the effect of sodium-glucose cotransporter 2 (SGLT-2) inhibition on constipation.
  • The underlying mechanisms linking SGLT-2 inhibition to constipation remain largely unknown.

Purpose of the Study:

  • To investigate the causal effect of SGLT-2 inhibition on constipation.
  • To explore the potential mediating role of circulating metabolites in this relationship.

Main Methods:

  • A two-sample Mendelian randomization (MR) study was conducted.
  • Genetic instruments for SGLT-2 inhibition were derived from SLC5A2 gene expression and HbA1c levels.
  • Summary-level data from large-scale genome-wide association studies (GWAS) for constipation and 452 metabolites were utilized.

Main Results:

  • Genetically proxied SGLT-2 inhibition showed a significant association with reduced constipation risk (OR 0.31).
  • The metabolite DSGEGDFXAEGGGVR was significantly associated with both SGLT-2 inhibition and constipation.
  • Mediation analysis revealed that DSGEGDFXAEGGGVR mediated 22.76% of the protective effect.

Conclusions:

  • This study provides genetic evidence for a causal link between SGLT-2 inhibition and decreased constipation incidence.
  • DSGEGDFXAEGGGVR is identified as a potential mediating metabolite in this pathway.
  • Findings suggest a novel pharmacological pathway for constipation management.
Keywords:
circulating metabolitesconstipationmendelian randomizationsodium-glucose cotransporter 2 inhibitiontype 2 diabetes mellitus

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