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The purpose of this systematic review and meta\u2010analysis was to evaluate the effect of MTF on weight and cardiometabolic parameters in adults with overweight\/obesity with or without nonalcoholic fatty liver disease (NAFLD) (CRD42018085512). We included randomized controlled trials (RCTs) in adults without diabetes mellitus, with mean body mass index (BMI)\u2009\u2265\u200925\u2009kg\/m\n                    <jats:sup>2<\/jats:sup>\n                    , with or without NAFLD, comparing MTF to placebo\/control, lifestyle modification (LSM) or a US Food and Drug Administration\u2010approved anti\u2010obesity drug, reporting on weight or metabolic parameters, and extending over at least 3\u2009months. We conducted a systematic search in MEDLINE, EMBASE, PubMed and the Cochrane Library without time limitation (until March 2022). We screened and selected eligible articles, abstracted relevant data, and assessed the risk of bias. All steps were in duplicate and independently. We conducted a random\u2010effects model meta\u2010analysis using Review Manager version 5.3, with prespecified subgroup analyses in case of heterogeneity. We identified 2650 citations and included 49 trials (55 publications). Compared to placebo, MTF was associated with a significant reduction in BMI (mean difference [MD] \u22120.56\u2009[\u22120.74, \u22120.37] kg\/m\n                    <jats:sup>2<\/jats:sup>\n                    ;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001), at doses ranging from 500 to 2550\u2009mg\/day, and with a significant percentage change in BMI of \u22122.53% (\u22122.90, \u22122.17) at the dose 1700\u2009mg\/day. There was no interaction by baseline BMI, MTF dose or duration, nor presence or absence of NAFLD. There was no significant difference between MTF and LSM. Orlistat was more effective than MTF (at doses of 1000\u20131700\u2009mg\/day) in terms of weight loss, with an MD in BMI of \u22123.17\u2009(\u22125.88; \u22120.47) kg\/m\n                    <jats:sup>2<\/jats:sup>\n                    , favouring the former. Compared to placebo\/control, MTF improved insulin parameters, while no effect was detected when compared to LSM. A few small trials showed heterogenous effects on liver parameters in patients with NAFLD treated with MTF compared to placebo\/control. There was a large variability in the expression of outcome measures and RCTs were of low quality. In conclusion, MTF was associated with a modest weight reduction in obese nondiabetic patients. Further high\u2010quality and better powered studies are needed to examine the impact of MTF in patients with insulin resistance and NAFLD.\n                  <\/jats:p>","DOI":"10.1111\/dom.15501","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:40:04Z","timestamp":1710204004000},"page":"1850-1867","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The impact of metformin on weight and metabolic parameters in patients with obesity: A systematic review and meta\u2010analysis of randomized controlled trials"],"prefix":"10.1111","volume":"26","author":[{"given":"Rachelle","family":"Haber","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Zarzour","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malak","family":"Ghezzawi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Saadeh","sequence":"additional","affiliation":[{"name":"Faculty of Medicine American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dania S.","family":"Bacha","sequence":"additional","affiliation":[{"name":"Faculty of Medicine American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lama","family":"Al Jebbawi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0012-986X","authenticated-orcid":false,"given":"Marlene","family":"Chakhtoura","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3755-8158","authenticated-orcid":false,"given":"Christos S.","family":"Mantzoros","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Medicine Boston VA Healthcare System  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014\u20103415"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.101882"},{"key":"e_1_2_11_4_1","unstructured":"FDA Zepbound leaflet accessed in February 2024.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/217806s000lbl.pdf"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/dmso.s95299"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11883\u2010016\u20100568\u20103"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2012.01.028"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010015\u20103844\u20109"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12812"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs20110386"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.03.014"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.7326\/m16\u20101860"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.12720"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12888\u2010016\u20101049\u20105"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc06\u20100560"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1370\/afm.343"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa012512"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20108587(15)00291\u20100"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1K656"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.581839"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2021357118"},{"key":"e_1_2_11_22_1","unstructured":"ChakhtouraM SaadehN GhosnA ZarzourF MantzorosC. 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