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Existing systematic reviews are largely confined to a single intervention category or to mixed populations, which limits targeted recommendations for adults in whom obesity itself, rather than an established metabolic comorbidity, is the principal clinical concern. This protocol describes a systematic review and network meta-analysis comparing dietary, physical activity, behavioural and pharmacological interventions in adults with simple obesity, pragmatically defined as trial populations in which obesity itself is the primary inclusion criterion. We will search PubMed, Embase and the Cochrane Library from inception to the search date for randomised controlled trials. Two reviewers will independently screen records, extract data and assess risk of bias using the Cochrane Risk of Bias 2 tool. The principal primary outcome will be percentage change in body weight at the end of an intervention period of at least 24 weeks. Key secondary outcomes will include the proportion of participants achieving at least 5% weight loss, separate measures of central obesity, and health-related quality of life. Pairwise and network meta-analyses will be conducted under a frequentist random-effects framework, and small-study effects will be examined with funnel plots and regression-based tests. Subgroup analyses and meta-regression will explore prespecified effect modifiers, and the credibility of important subgroup findings will be judged with the ICEMAN instrument. Certainty of evidence will be assessed using the GRADE framework. Depending on the quality, consistency and certainty of the available evidence, the findings may inform clinical decision-making, future guideline development and research priorities. This review is registered with PROSPERO (CRD420251236477).<\/jats:p>","DOI":"10.1371\/journal.pone.0351589","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:26:45Z","timestamp":1791480405000},"page":"e0351589","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systematic review and network meta-analysis of interventions for adults with simple obesity: Study protocol"],"prefix":"10.1371","volume":"21","author":[{"given":"Lingyao","family":"Sun","sequence":"first","affiliation":[{"name":"China Pharmaceutical University","place":["Nanjing, China"],"department":["Centre for Pharmacoeconomics and Outcomes Research"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhen","family":"Xu","sequence":"additional","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital","place":["Fuzhou, China"],"department":["Department of Endocrinology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dachuang","family":"Zhou","sequence":"additional","affiliation":[{"name":"China Pharmaceutical University","place":["Nanjing, China"],"department":["Centre for Pharmacoeconomics and Outcomes Research"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia, Medica, Chinese Academy of Sciences","place":["Shanghai, China"],"department":["Molecular Imaging Center, State Key Laboratory of Drug Research"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Yin","sequence":"additional","affiliation":[{"name":"University of Macau","place":["Macau, China"],"department":["Faculty of Health Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Ye","sequence":"additional","affiliation":[{"name":"China Pharmaceutical University","place":["Nanjing, China"],"department":["Centre for Pharmacoeconomics and Outcomes Research"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5364-2061","authenticated-orcid":true,"given":"Lei","family":"Tian","sequence":"additional","affiliation":[{"name":"China Pharmaceutical University","place":["Nanjing, China"],"department":["Centre for Pharmacoeconomics and Outcomes Research"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"pone.0351589.ref001","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa1614362","article-title":"Health effects of overweight and obesity in 195 countries over 25 years","volume":"377","author":"A Afshin","year":"2017","journal-title":"N Engl J Med"},{"key":"pone.0351589.ref002","unstructured":"Obesity WPRO. 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