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Related Experiment Video

Updated: Apr 9, 2026

Electroacupuncture Combined with Chinese Medicine Ironing Therapy for Functional Constipation

Electroacupuncture Combined with Chinese Medicine Ironing Therapy for Functional Constipation

Published on: July 5, 2024

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

Summary

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.

Keywords:

circulating metabolites constipation mendelian randomization sodium-glucose cotransporter 2 inhibition type 2 diabetes mellitus

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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.