{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:04:57Z","timestamp":1792267497769,"version":"4.4.0"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T00:00:00Z","timestamp":1673913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To assess the safety, tolerability and pharmacodynamics (PD) of the ketohexokinase inhibitor PF\u201006835919 in participants with non\u2010alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>This double\u2010blind, placebo\u2010controlled, parallel\u2010group study enrolled adults with NAFLD (\u2265\u20098% whole liver fat [WLF] using MRI proton density fat fraction [MRI\u2010PDFF]) and T2D on stable doses of metformin (\u2265\u2009500\u2009mg\/day). Participants received once\u2010daily placebo, PF\u201006835919 150\u2009or 300\u2009mg for 16\u2009weeks. Randomization (1:1:1) was via an interactive response technology system. Endpoints included percentage change from baseline (CFB) in WLF using MRI\u2010PDFF (primary endpoint) and CFB in HbA1c (co\u2010primary endpoint) at 16\u2009weeks, PD, safety and tolerability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 164 participants randomized and treated, 145 completed the treatment (placebo, n\u00a0=\u00a050; PF\u201006835919 150\u2009mg, n\u00a0=\u00a046; PF\u201006835919 300\u2009mg, n\u00a0=\u00a049). At week 16, least squares mean (90% confidence interval) percentage CFB in WLF was \u22125.26% (\u221212.86%, 2.99%), \u221217.05% (\u221224.01%, \u22129.46%) and \u221219.13% (\u221225.51%, \u221212.20%) in the placebo, PF\u201006835919 150\u2010mg and 300\u2010mg groups, respectively (PF\u201006835919 300\u2010mg group vs. placebo,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.0288). Modest numerical reductions in HbA1c were observed in all groups that did not reach statistical significance. Treatment\u2010emergent adverse event incidence was similar across groups (40.7%, 45.5% and 32.7% in the placebo, PF\u201006835919 150\u2010mg and 300\u2010mg groups, respectively), with no apparent dose\u2010related trend.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PF\u201006835919 administration over 16\u2009weeks was generally safe and well tolerated and resulted in reductions in WLF in participants with NAFLD and T2D.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14946","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T06:05:46Z","timestamp":1670997946000},"page":"992-1001","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["A phase 2a, randomized, double\u2010blind, placebo\u2010controlled, three\u2010arm, parallel\u2010group study to assess the efficacy, safety, tolerability and pharmacodynamics of\n                    <scp>PF<\/scp>\n                    \u201006835919 in patients with non\u2010alcoholic fatty liver disease and type 2 diabetes"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6017-1838","authenticated-orcid":false,"given":"Aditi R.","family":"Saxena","sequence":"first","affiliation":[{"name":"Pfizer Worldwide Research and Development  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie\u2010An","family":"Lyle","sequence":"additional","affiliation":[{"name":"Early Clinical Development Pfizer Inc  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaivan","family":"Khavandi","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research and Development  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruolun","family":"Qiu","sequence":"additional","affiliation":[{"name":"Early Clinical Development Pfizer Inc  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Whitlock","sequence":"additional","affiliation":[{"name":"Early Clinical Development Pfizer Inc  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4783-8620","authenticated-orcid":false,"given":"William P.","family":"Esler","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research and Development  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5269-2155","authenticated-orcid":false,"given":"Albert M.","family":"Kim","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research and Development  Cambridge Massachusetts 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