{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:19:33Z","timestamp":1791566373091,"version":"4.3.4"},"reference-count":48,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012187","name":"St. Vincent's Clinic Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012187","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>This study investigated the safe use of metformin in patients with (1) type 2 diabetes mellitus (T2DM) and heart failure on metformin, and (2) heart failure without T2DM and metformin na\u00efve.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two prospective studies on heart failure patients were undertaken. The first was a cross\u2010sectional study with two patient cohorts, one with T2DM on metformin (n\u2009=\u200944) and one without T2DM metformin naive (n\u2009=\u200947). The second was a 12\u2010week interventional study of patients without T2DM (n\u2009=\u200927) where metformin (500\u2009mg immediate release, twice daily) was prescribed. Plasma metformin and lactate concentrations were monitored. Individual pharmacokinetics were compared between cohorts. Univariable and multivariable analysis analysed the effects of variables on plasma lactate concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Plasma metformin and lactate concentrations mostly (99.9%) remained below safety thresholds (5\u00a0mg\/L and 5\u00a0mmol\/L, respectively). Metformin concentration had no significant relationship with lactic acidosis safety markers. In the interventional study, New York Heart Association (NYHA) II (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.03) and III (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001) grading was associated with higher plasma lactate concentrations, whereas male sex was associated with 47% higher plasma lactate concentrations (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05). The pharmacokinetics of heart failure patients with and without T2DM were similar.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We observed no unsafe plasma lactate concentrations in patients with heart failure treated with metformin. Metformin exposure did not influence plasma lactate concentrations, but NYHA class and sex did. The pharmacokinetics of metformin in heart failure patients are similar irrespective of T2DM. These findings may support the safe use of metformin in heart failure patients with and without T2DM.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15737","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T06:29:41Z","timestamp":1680676181000},"page":"2603-2613","source":"Crossref","is-referenced-by-count":6,"title":["The safe use of metformin in heart failure patients both with and without T2DM: A cross\u2010sectional and longitudinal study"],"prefix":"10.1111","volume":"89","author":[{"given":"Gina","family":"Chowdhury","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology &amp; Toxicology St Vincent's Hospital Sydney  Sydney Australia"},{"name":"School of Medical Science The University of New South Wales  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1456-876X","authenticated-orcid":false,"given":"Jane E.","family":"Carland","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology &amp; 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