{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T19:03:10Z","timestamp":1777662190246,"version":"3.51.4"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To characterize the drug-drug interaction (DDI) profile of the novel, long-acting GLP-1 receptor agonist ecnoglutide (XW003) with two widely co-prescribed drugs: metformin and narrow therapeutic index agent, warfarin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this open-label, fixed-sequence, crossover study, 28 healthy participants received a single dose of warfarin and multiple doses of metformin, both with and without steady-state XW003 coadministration. The primary endpoint was the comparison of systemic exposure, assessed by whether the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of key pharmacokinetic (PK) parameters fell within the 80.00%\u2013125.00% no-effect bounds. The pharmacodynamic (PD) impact on warfarin was evaluated via International Normalized Ratio (INR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Coadministration of XW003 did not clinically alter the total systemic exposure (AUC) of metformin or of either S- or R-warfarin enantiomer, as all corresponding GMRs and 90% CIs for AUC met the pre-specified no-effect criteria. While modest reductions in C\n                      <jats:sub>max<\/jats:sub>\n                      and delays in T\n                      <jats:sub>max<\/jats:sub>\n                      were observed for both object drugs, warfarin\u2019s anticoagulant activity remained unaffected, with INR profiles showing no clinically relevant changes. The safety profile of XW003 was consistent with the GLP-1 receptor agonist class.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The findings demonstrate the absence of a clinically significant interaction between XW003 and either metformin or warfarin. This supports the concomitant use of XW003 with these medications without dose adjustment, providing crucial evidence for its safe application in real-world clinical practice where polypharmacy is common.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1816593","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:28:32Z","timestamp":1777447712000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["No dose adjustment required for warfarin or metformin when coadministered with the novel GLP-1 receptor agonist ecnoglutide: an open-label, fixed-sequence, crossover study"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhuo","family":"Chen","sequence":"first","affiliation":[{"name":"Institution of National Drug Clinical Trial, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"NMPA Key Laboratory for Technical 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