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<p>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%; <i>p</i> = 0.01), decreasing from 64.2% to 62.1%. Mean INR did not change (0.00; 95% CI, -0.02 to 0.03; <i>p</i> = 0.79). INR recheck frequency increased slightly, with a mean interval decrease of 0.7 days (95% CI -1.4 to 0.0; <i>p</i> = 0.049). Time below therapeutic range increased by 0.8% (<i>p</i> = 0.25), time above therapeutic range increased by 1.3% (<i>p</i> = 0.04), and INR standard deviation increased by 0.03 (<i>p</i> = 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.</p> Graphical Abstract <p>The increasing use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) raises concern about potential interactions with narrow therapeutic index medications such as warfarin. This retrospective cohort study evaluated changes in time in therapeutic range (TTR) among patients receiving warfarin during the 6 months before and after GLP-1 RA initiation, using real-world data from the TriNetX Research Network. Among 1,021 patients, mean TTR decreased by 2.1% after GLP-1 RA initiation, while mean international normalized ratio (INR) remained unchanged. Given the potential for increased INR variability, clinicians may consider increasing INR monitoring frequency following GLP-1 RA initiation.</p>

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

  • 期刊论文

  • 发表日期：

    2026年5月11日

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  • Spencer J. Gilbert,
  • Sara R. Vazquez,
  • Ramkiran Gouripeddi,
  • Alexander Millar,
  • Julio C. Facelli,
  • Daniel M. Witt

摘要

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.

Graphical Abstract

The increasing use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) raises concern about potential interactions with narrow therapeutic index medications such as warfarin. This retrospective cohort study evaluated changes in time in therapeutic range (TTR) among patients receiving warfarin during the 6 months before and after GLP-1 RA initiation, using real-world data from the TriNetX Research Network. Among 1,021 patients, mean TTR decreased by 2.1% after GLP-1 RA initiation, while mean international normalized ratio (INR) remained unchanged. Given the potential for increased INR variability, clinicians may consider increasing INR monitoring frequency following GLP-1 RA initiation.