{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T08:47:35Z","timestamp":1790412455404,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"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":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This randomized, double\u2010blind, placebo\u2010controlled Phase 2b study aimed to assess the efficacy, safety, and tolerability of danuglipron (PF\u201006882961), an oral small\u2010molecule glucagon\u2010like peptide\u20101 (GLP\u20101) receptor agonist, in adults with obesity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Eligible participants (aged 18\u201375\u2009years; with obesity, without diabetes) were randomized to receive danuglipron or placebo twice daily (BID) for 26 or 32\u2009weeks. Danuglipron was escalated to doses of 40\u2013200\u2009mg BID in 1\u2010, 2\u2010, or 4\u2010week intervals. Assessments included body weight, waist circumference, and safety evaluations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, 628 participants were randomized; of 626 receiving study treatment (placebo,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200990; danuglipron,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009536), 39.3% completed treatment. Approximately 38% of participants discontinued treatment because of adverse events (AEs)\u00a0and 22% discontinued for other reasons. The primary endpoint was the change in weight from baseline to the end of treatment; all danuglipron groups demonstrated statistically significant reductions with least squares mean percentage decreases from baseline ranging from \u22125.0% (90% confidence interval [CI] \u22126.8%, \u22123.2%) to \u221212.9% (90% CI \u221216.1%, \u22129.5%) relative to placebo. Danuglipron was considered safe. Consistent with the mechanism, the most frequently reported events were nausea and vomiting, and increased rates of gastrointestinal\u00a0AEs were generally observed at higher doses. Most events were reported as mild, and no other dose\u2010related trends were observed in safety endpoints.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In participants with obesity, danuglipron resulted in statistically significant and clinically meaningful reductions in body weight versus placebo over 26 or 32\u2009weeks. The overall safety profile observed in this study was consistent with expectations for the mechanism, although discontinuation rates due to AEs were higher than anticipated across all treatment groups, including placebo.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>ClinicalTrials.gov identifier<\/jats:bold>\n                      : NCT04707313.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.16534","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T05:03:46Z","timestamp":1750395826000},"page":"4915-4926","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Efficacy and safety of danuglipron (\n                    <scp>PF<\/scp>\n                    \u201006882961) in adults with obesity: A randomized, placebo\u2010controlled, dose\u2010ranging phase 2b study"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8578-8639","authenticated-orcid":false,"given":"Clare","family":"Buckeridge","sequence":"first","affiliation":[{"name":"Pfizer Research and Development  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Cobain","sequence":"additional","affiliation":[{"name":"Pfizer Research and Development  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold E.","family":"Bays","sequence":"additional","affiliation":[{"name":"Louisville Metabolic and Atherosclerosis Research Center University of Louisville School of Medicine  Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Medical Corporation Heishinkai ToCROM Clinic  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Fukuwa Clinic  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Halstead","sequence":"additional","affiliation":[{"name":"Pfizer Research and Development  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Tsamandouras","sequence":"additional","affiliation":[{"name":"Pfizer Research and Development  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Sherry","sequence":"additional","affiliation":[{"name":"Pfizer Research and Development  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donal N.","family":"Gorman","sequence":"additional","affiliation":[{"name":"Pfizer Research and Development  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6017-1838","authenticated-orcid":false,"given":"Aditi R.","family":"Saxena","sequence":"additional","affiliation":[{"name":"Pfizer Research and Development  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c01856"},{"key":"e_1_2_10_3_1","unstructured":"SAXENDA\u00ae (liraglutide) Prescribing Information.Novo Nordisk Bagsvaert Denmark.2023.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/206321s016lbl.pdf. Accessed August 14 2024."},{"key":"e_1_2_10_4_1","unstructured":"WEGOVY\u00ae (semaglutide) Prescribing Information.Novo Nordisk Bagsvaert Denmark.2024.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/215256s011lbl.pdf. Accessed August 14 2024."},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14487"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14928"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01391-w"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15168"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.14493"},{"key":"e_1_2_10_10_1","unstructured":"Pfizer.Pfizer provides update on oral GLP\u20101 receptor agonist danuglipron.2025.https:\/\/www.pfizer.com\/news\/press-release\/press-release-detail\/pfizer-provides-update-oral-glp-1-receptor-agonist. 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