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We conducted a comprehensive meta\u2010analysis of randomized studies on once\u2010weekly semaglutide in this patient population. We identified nine studies with 11,641 patients in the semaglutide group and 10,479 in the placebo group. We observed that semaglutide resulted in significant benefits, including change in body weight (%): mean difference (MD) of \u221211.49% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), change in absolute body weight: MD of \u221211.74\u2009kg (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), and change in waist circumference: MD of \u22129.06\u2009cm (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Gastrointestinal side effects are predominant including nausea: odds ratio (OR) of 4.06 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), vomiting: OR of 4.43 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), diarrhea: OR of 2.10 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), constipation: OR of 2.43 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), gallbladder disorders: OR of 1.26 (<jats:italic>p<\/jats:italic>\u2009=\u20090.010), and cholelithiasis: OR of 2.06 (<jats:italic>p<\/jats:italic>\u2009=\u20090.04). Serious adverse events were not statistically significant: OR of 1.06 (<jats:italic>p<\/jats:italic>\u2009=\u20090.82). However, the percentage of participants discontinuing due to adverse events and gastrointestinal side effects was statistically significant: ORs of 2.22 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) and 3.77 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), respectively. This study shows that in patients with overweight or obesity without DM, once\u2010weekly subcutaneous semaglutide can significantly decrease body weight without risk of serious adverse events when compared with a placebo. However, gastrointestinal side effects are predominant with semaglutide, which can result in medication discontinuation.<\/jats:p>","DOI":"10.1111\/obr.13792","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T02:44:55Z","timestamp":1719197095000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Efficacy and safety of once\u2010weekly subcutaneous semaglutide on weight loss in patients with overweight or obesity without diabetes mellitus\u2014A systematic review and meta\u2010analysis of randomized controlled trials"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4430-9830","authenticated-orcid":false,"given":"Sharath","family":"Kommu","sequence":"first","affiliation":[{"name":"Department of Hospital Medicine Marshfield Clinic Health System  Rice Lake Wisconsin USA"},{"name":"Department of Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3732-0716","authenticated-orcid":false,"given":"Richard L.","family":"Berg","sequence":"additional","affiliation":[{"name":"Office of Research Computing and Analytics Marshfield Clinic Research Institute  Marshfield Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,23]]},"reference":[{"issue":"2","key":"e_1_2_10_2_1","first-page":"51S","article-title":"Evaluation, and treatment of overweight and obesity in adults\u2014the evidence report","volume":"6","author":"Clinical Guidelines on the Identification","year":"1998","journal-title":"Nat Inst Health Obes Res"},{"key":"e_1_2_10_3_1","unstructured":"FryarCD CarrollMD AffulJ.Prevalence of overweight obesity and severe obesity among adults aged 20 and over: United States 1960\u20131962 through 2017\u20132018.2020. 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