{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T05:10:57Z","timestamp":1791781857306,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp;amp; Metabol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Obesity represents a major global health challenge, contributing substantially to cardiovascular disease and metabolic complications. Orforglipron, a novel oral non\u2010peptide GLP\u20101 receptor agonist, has emerged as a promising therapeutic option for weight management and glycemic control. This meta\u2010analysis evaluated the efficacy and safety of orforglipron in obese patients with or without type 2 diabetes mellitus (T2DM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library and\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      from inception to October 2025 to identify randomised controlled trials (RCTs) evaluating orforglipron in obese patients. Mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random\u2010effects models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Five RCTs comprising 4410 participants were included. Orforglipron demonstrated dose\u2010dependent reductions in body weight from 2.48% at 3\u2009mg to 9.8% at 45\u2009mg, BMI from 0.89 to 3.62\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , waist circumference from 1.57 to 6.9\u2009cm, and HbA1c from 0.76% to 1.04% compared with placebo. Favourable lipid changes included reductions in total cholesterol (MD: \u22124.51% [95% CI: \u22126.91 to \u22122.11]), LDL\u2010C (MD: \u22125.34% [95% CI: \u22127.10 to \u22123.58]), and triglycerides (MD: \u221210.07% [95% CI: \u221212.33 to \u22127.80]), with increased HDL\u2010C (MD: 2.94% [95% CI: 1.38 to 4.49]). However, gastrointestinal adverse events were significantly more frequent at doses of 12\u2009mg or higher and treatment discontinuation rates were highest at 24\u2009mg (RR:4.61 [95% CI:1.6 to 13.33]) and 36\u2009mg (RR:3.68 [95% CI:2.48 to 5.44]) doses. Serious adverse events and mortality rates were comparable to those with placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Orforglipron significantly improved glycemic and lipid parameters in patients with obesity, demonstrating dose\u2010dependent efficacy with maximal benefits at higher doses. While gastrointestinal tolerability remains a clinically important limitation requiring mitigation strategies, orforglipron represents a promising oral therapeutic option for comprehensive obesity and metabolic management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/edm2.70134","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T18:40:24Z","timestamp":1764182424000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Efficacy and Safety of Orforglipron in Obese Adults With or Without Diabetes: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"8","author":[{"given":"Ravi Kumar","family":"Pandey","sequence":"first","affiliation":[{"name":"Nepalgunj Medical College  Nepalgunj Lumbini Province Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahnoor","family":"Jan","sequence":"additional","affiliation":[{"name":"Shaikh Khalifa Bin Zayed Al\u2010Nahyan Medical and Dental College  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aqsa","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Rawalpindi Medical University  Rawalpindi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khawaja Arham","family":"Jawaid","sequence":"additional","affiliation":[{"name":"Sharif Medical City Hospital  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mawra","family":"Naveed","sequence":"additional","affiliation":[{"name":"Shaikh Khalifa Bin Zayed Al\u2010Nahyan Medical and Dental College  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Ali","family":"Abid","sequence":"additional","affiliation":[{"name":"King Edward Medical University  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah Bin","family":"Amir","sequence":"additional","affiliation":[{"name":"King Edward Medical University  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shafique","family":"Ahmed","sequence":"additional","affiliation":[{"name":"International University of Kyrgyzstan  Bishkek Kyrgyzstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7773-2605","authenticated-orcid":false,"given":"Muhammad","family":"Safiullah","sequence":"additional","affiliation":[{"name":"King Edward Medical University  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9381-0106","authenticated-orcid":false,"given":"Muhammad Imaz","family":"Bhatti","sequence":"additional","affiliation":[{"name":"King Edward Medical University  Lahore 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