{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T17:50:58Z","timestamp":1782150658123,"version":"3.54.5"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\n Background<\/jats:title>\n Patients with type 2 diabetes mellitus (T2DM) usually accompany with the occurrence of high blood pressure, necessitating a combination of treatments. This includes sodium-glucose co-transporter 2(SGLT2) inhibitors like empagliflozin, ertugliflozin, and henagliflozin, and antihypertensives like telmisartan. Both classes interact with transporters like P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), with telmisartan further inhibiting several, including organic anion transporting poly-peptide (OATP) 1B1\/1B3.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n Despite their common use, pharmacokinetic interactions between these drugs remain underexplored. This study aims to investigate the potential pharmacokinetic interaction between three specific SGLT2 inhibitors and telmisartan.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Rats were divided into twelve groups, with six rats per group, and received different combinations of empagliflozin, ertugliflozin, henagliflozin, and telmisartan. Drug concentrations were measured using ultra-performance liquid chromatography-tandem mass spectrometry, and mRNA expressions through quantitative reverse transcription polymerase chain reaction (RT-qPCR).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Our study manifested that telmisartan increased the plasma concentration-time curves (AUC\n 0-t<\/jats:sub>\n and AUC\n 0\u2013\u221e<\/jats:sub>\n ) and the maximum plasma concentrations (C\n max<\/jats:sub>\n ) of empagliflozin, whereas the apparent clearance (CL\n z\/F<\/jats:sub>\n ) and apparent volume of distribution (V\n z<\/jats:sub>\n ) significantly decreased(all\n p<\/jats:italic>\n \u2009\uff1c\u20090.05). Similarly, telmisartan increased the AUC\n 0-t<\/jats:sub>\n , AUC\n 0-\u221e<\/jats:sub>\n and C\n max<\/jats:sub>\n of henagliflozin and decreased the CL\n z\/F<\/jats:sub>\n (all\n p<\/jats:italic>\n \u2009\uff1c\u20090.05). When coadministered with ertugliflozin or henagliflozin, the AUC\n 0-t<\/jats:sub>\n and AUC\n 0\u2013\u221e<\/jats:sub>\n of telmisartan decreased significantly and the CL\n z\/F<\/jats:sub>\n increased significantly(all\n p<\/jats:italic>\n \u2009\uff1c\u20090.05). Furthermore, PCR results demonstrated that telmisartan decreased the expression of BCRP expression in liver, intestines and kidney, P-gp expression in the intestines and kidney and OATP1B2 expression in liver tissue.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our findings highlight the importance of these drug interactions, which could inform dose adjustments to enhance safety in patients with T2DM and hypertension.<\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0350400","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T17:32:49Z","timestamp":1782149569000},"page":"e0350400","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic interactions between three SGLT2 inhibitors and telmisartan: A focus on empagliflozin, ertugliflozin, and henagliflozin"],"prefix":"10.1371","volume":"21","author":[{"given":"Xin","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanru","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caihui","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5349-4970","authenticated-orcid":true,"given":"Zhanjun","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"issue":"12","key":"pone.0350400.ref001","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.2337\/dci18-0033","article-title":"Management of hyperglycemia in type 2 diabetes, 2018. 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