Evaluating the indirect interaction between glucagon-like peptide-1 receptor agonists and warfarin using real-world...

Increasing use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) raises concern for interactions with warfarin. Although GLP-1 RAs do not affect warfarin pharmacokinetics, their appetite-reducing effects may decrease vitamin K intake and increase International Normalized Ratio (INR) variability. Large-scale real-world data (RWD) are needed to evaluate these effects. To evaluate changes in time-in-therapeutic INR range (TTR) among warfarin patients initiated on GLP-1 RA therapy. This retrospective cohort study evaluated TTR 6 months before and after GLP-1 RA initiation using RWD from the TriNetX Research Network. Included patients were required to have evidence of warfarin use before and after GLP-1 RA initiation. Primary outcomes included changes in TTR, INR, and INR recheck frequency. Secondary outcomes included time below and above the therapeutic range and INR variability. Of 53,943 patients screened, 1,021 met inclusion criteria. Mean TTR decreased by 2.1% (95% CI, -3.7% to -0.6%; p = 0.01), decreasing from 64.2% to 62.1%. Mean INR did not change (0.00; 95% CI, -0.02 to 0.03; p = 0.79). INR recheck frequency increased slightly, with a mean interval decrease of 0.7 days (95% CI -1.4 to 0.0; p = 0.049). Time below therapeutic range increased by 0.8% (p = 0.25), time above therapeutic range increased by 1.3% (p = 0.04), and INR standard deviation increased by 0.03 (p = 0.051). GLP-1 RA initiation was associated with a modest decrease in TTR and increased INR variability among warfarin-treated patients. Clinicians may consider closer INR monitoring following GLP-1 RA initiation.