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Random-effects meta-analyses were used to derive effect sizes: event rates.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>From 7019 publications, we identified 211 potentially eligible full-text articles. Ultimately, 21 observational studies were included in the meta-analysis. The prevalence of GI AE was as follows: diarrhea 6.9% (95% CI: 0.038\u20130.123), bloating 6,2% (95% CI: 0.020\u20130.177), abdominal pain 5,3% (95% CI: 0.003\u20130.529), vomiting 2.4% (95%: CI 0.007\u20130.075), constipation 1.1% (95%: CI 0.001\u20130.100). The incidence of bloating (coefficient -4.46; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), diarrhea (coefficient -1.17; <jats:italic>p<\/jats:italic>\u2009=\u20090.0951) abdominal pain (coefficient -2.80; <jats:italic>p<\/jats:italic>\u2009=\u20090.001), constipation (coefficient -5.78; <jats:italic>p<\/jats:italic>\u2009=\u20090.0014) and vomiting (coefficient -2.47; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) were lower for extended release (XR) metformin than metformin immediate release (IR) formulation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study highlights the prevalence of GI AE in patients receiving metformin, with a diarrhea predominance, followed by bloating, diarrhea, abdominal pain, constipation, and vomiting. The incidence is lower in patients administered with XR metformin.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.crd.york.ac.uk\/prospero\/display_record.php?ID=CRD42021289975\">https:\/\/www.crd.york.ac.uk\/prospero\/display_record.php?ID=CRD42021289975<\/jats:ext-link>, identifier CRD42021289975.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12902-024-01727-w","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T08:02:51Z","timestamp":1727683371000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Gastrointestinal adverse events of metformin treatment in patients with type 2 diabetes mellitus: a systematic review and meta-analysis with meta-regression of observational studies"],"prefix":"10.1186","volume":"24","author":[{"given":"Katarzyna","family":"Nabrdalik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirela","family":"Hendel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Irlik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Kwiendacz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"\u0141oniewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Bucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uazman","family":"Alam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory Y. 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