{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T09:03:04Z","timestamp":1785229384212,"version":"3.55.0"},"reference-count":61,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp; Metabol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aim<\/jats:title>\n                    <jats:p>Orforglipron (OFG), an oral, non\u2010peptide glucagon\u2010like peptide\u20101 receptor agonist (GLP\u20101 RAs), showed potential benefits for type 2 diabetes mellitus (T2DM) and obesity. Its dose\u2013response effects on body weight\u2010related parameters and glycemic outcomes remain incompletely analysed. This network meta\u2010analysis aims to address this gap across multiple doses of OFG (3, 12, 24, 36 and 45\u2009mg) in adults with or without T2DM at 12, 26 and 36\u2009weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PRISMA guidelines were followed in our study. Embase, PubMed, Web of Science and Scopus were searched for randomised controlled trials. Random\u2010effects models expressed OFG effects as odds ratios (OR), mean difference (MD) and standardised mean difference (SMD) with 95% confidence intervals (95% CI). RStudio software (version 4.5.1) was used for analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Six RCTs comprising 4878 participants were included. OFG demonstrated reductions in body weight, BMI and waist circumference across all follow\u2010ups. OFG 45\u2009mg dose produced the greatest effects in body weight (SMD: \u22121.71\u2009kg at 12\u2009weeks, MD: \u22128.81\u2009kg at 26\u2009weeks and MD: \u221212.13\u2009kg at 36\u2009weeks vs. placebo). Categorical weight\u2010loss analyses showed that individuals receiving 24\u201345\u2009mg increased the odds to achieve \u2265\u20095%, \u2265\u200910% and \u2265\u200915% weight loss at 26\u2009weeks. Glycemic outcomes improved across all doses, with the greatest HbA1c reduction at 45\u2009mg (\u22121.65%; 95% CI \u22121.98 to \u22121.32) and greatest fasting glucose improvement at 36\u2009mg dose. Treatment\u2010emergent adverse events increased with dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>OFG demonstrated improvements in weight\u2010related outcomes and glycemic outcomes. Adverse events increased with dose, consistent with expected class tolerability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/edm2.70275","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T04:32:18Z","timestamp":1784781138000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic and Glycemic Effects of Orforglipron, a\n                    <scp>GLP<\/scp>\n                    \u20101 Receptor Agonist, in Adults With or Without Diabetes: A Network Meta\u2010Analysis of Randomised Clinical Trials"],"prefix":"10.1002","volume":"9","author":[{"given":"Ahmed W.","family":"Hageen","sequence":"first","affiliation":[{"name":"Faculty of Medicine Tanta University  Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5802-2291","authenticated-orcid":false,"given":"Ahmed 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