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However, the AUC of the victim drugs were not altered by GLP-1 RA administration in most cases, suggesting that clinically significant DDIs are unlikely to occur.124 Conversely, both the C max and AUC of statins decreased by 28–70% and 0–40%, respectively, after GLP-1 RA subcutaneous administration.140,147,153,155,159 However, statins are known to exhibit high interindividual variability in terms of pharmacokinetics, and GLP-1 RA administration did not affect the lipid-lowering effect of statins in clinical studies, indicating minimal clinical significance.147,164 Moreover, the AUC of metformin increased by 32%, while the C max of metformin remained unchanged following oral semaglutide administration.158 In addition, the C max and AUC of furosemide were decreased by 34% and increased by 28%, respectively.140 Due to metformin and furosemide’s wide therapeutic index, the risk of clinically significant DDIs is low.140,158 Administration of SNAC, the absorption enhancer for oral semaglutide, did not alone alter exposure to lisinopril, warfarin, digoxin, or metformin
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Survival analyses–i.e., Cox model, Kaplan-Meier estimator, and Aalen’s additive hazards regression–were performed using packages “Survival” (v
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