Mediation analysis indicated that DSGEGDFXAEGGGVR significantly mediated 22.76% of the protective effect.<h4>Conclusion</h4>This study provides genetic support for a causal relationship between SGLT-2 inhibition and reduced constipation risk, and identifies DSGEGDFXAEGGGVR as a potential mediating metabolite. The gene discussed is SLC5A2; the disease is Constipation.