Genetic evidence for a causal protective effect of GLP-1 receptor agonists on paralytic ileus but not on other gastrointestinal events.

The association between genetically proxied GLP1RA using 6 SNPs as the instrument and decreased risk of ileus was nominally significant (IVW: P = 2.11 × 10 −2 ; weighted median: P = 1.86 × 10 −2 ; weighted mode: P = 7.80 × 10 −2 ; simple mode: P = 1.57 × 10 -1 ) (Fig. 3 , Table S1, Supplemental Digital Content, https://links.lww.com/MD/R558 ).

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However, another analysis based on data from 3 European countries did not confirm this signal, suggesting that the increased risk associated with GLP-1RAs may not be significant compared to sodium-glucose cotransporter-2 inhibitors among T2DM patients.

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In the multivariable-adjusted model, the GLP1-RA PGS was inversely associated with the risk of paralytic ileus but did not reach statistical significance, likely due to a limited number of events (Fig. 4 ).

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