{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T19:48:24Z","timestamp":1787600904441,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Glucagon-like peptide-1 receptor agonist (GLP-1RA)- and incretin-based therapies are now central to obesity management. Their clinical value, however, should be interpreted beyond total weight loss, because changes in fat mass, lean mass, physical function, and cardiometabolic risk may depend on the accompanying dietary, behavioral, and exercise co-interventions. This systematic review and meta-analysis evaluated GLP-1RA- and incretin-based therapies delivered within lifestyle interventions in adults with overweight or obesity. Methods: The protocol was registered in PROSPERO (CRD420261360837). PubMed\/MEDLINE, Web of Science, Scopus, CINAHL, SPORTDiscus, and CENTRAL were searched from inception to the final search dates. Records were deduplicated in Zotero. Risk of bias was assessed using the Cochrane RoB 2 tool. Random-effects meta-analyses were estimated using restricted maximum likelihood with Hartung\u2013Knapp adjustment when pooling was appropriate. Results: Across all database sources, 1651 records were identified. After removing 113 duplicate records and 212 records with an ineligible publication type before screening, 1326 records were screened. Seventy-seven reports were sought for retrieval, five were not retrieved, 72 were assessed at full text, and 48 reports corresponding to 35 independent parent trials or trial clusters were retained for qualitative synthesis. The primary kilogram-scale meta-analysis included eight independent comparisons and showed greater body-weight reduction with GLP-1RA\/incretin-based therapy delivered within a lifestyle background than with placebo\/control (mean difference [MD] \u221210.08 kg, 95% confidence interval [CI] \u221212.76 to \u22127.39; 95% prediction interval [PI] \u221217.86 to \u22122.29; I2 = 95.6%). Percentage body-weight change was analyzed separately across 11 independent comparisons and also favored GLP-1RA\/incretin-based therapy (MD \u22129.53 percentage points, 95% CI \u221211.92 to \u22127.14; 95% PI \u221217.58 to \u22121.48; I2 = 95.4%). Conclusions: GLP-1RA- and incretin-based therapies delivered within lifestyle interventions are associated with clinically meaningful reductions in body weight in adults with overweight or obesity. Absolute and relative body-weight change metrics should remain analytically separate. The magnitude of benefit varies across trial contexts, and certainty remains limited by risk-of-bias concerns and considerable heterogeneity. Future trials should standardize the reporting of lifestyle co-interventions, body composition, adherence, physical-function outcomes, and safety monitoring.<\/jats:p>","DOI":"10.3390\/nu18111781","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:19:42Z","timestamp":1780316382000},"page":"1781","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["GLP-1RA- and Incretin-Based Therapies Within Lifestyle Interventions for Adults with Overweight or Obesity: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7697-419X","authenticated-orcid":false,"given":"Alejandro","family":"Bruna-Mejias","sequence":"first","affiliation":[{"name":"Programa de Doctorado en Investigaci\u00f3n Aplicada a las Ciencias Sanitarias, Escuela de Doctorado, Universidad de Las Palmas de Gran Canaria (ULPGC), 35001 Las Palmas de Gran Canaria, Spain"},{"name":"Escuela de Medicina, Facultad de Medicina, Universidad Andr\u00e9s Bello, Vi\u00f1a del Mar 2520000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Jos\u00e9","family":"Valenzuela-Fuenzalida","sequence":"additional","affiliation":[{"name":"Escuela de Medicina, Facultad de Medicina, Universidad Andr\u00e9s Bello, Vi\u00f1a del Mar 2520000, Chile"},{"name":"Department of Chemical and Biological Sciences, Faculty of Health Sciences, Universidad Bernardo O\u2019Higgins, Santiago 8370993, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Oyanedel","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Universidad Aut\u00f3noma de Chile, Santiago 8910060, Chile"},{"name":"Faculty of Health and Social Sciences, Universidad de Las Am\u00e9ricas, Santiago 8370040, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Figueroa-Puig","sequence":"additional","affiliation":[{"name":"School of Kinesiology, Faculty of Medicine, Universidad Mayor, Santiago 7500000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Jos\u00e9","family":"Cabezas-Salgado","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad Cat\u00f3lica del Maule, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1781-062X","authenticated-orcid":false,"given":"Mathias","family":"Orellana-Donoso","sequence":"additional","affiliation":[{"name":"School of Medicine, Universidad Finis Terrae, Santiago 7501015, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6497-3480","authenticated-orcid":false,"given":"Gloria","family":"Cifuentes-Suazo","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Carrera de Odontolog\u00eda, Universidad Cat\u00f3lica de la Sant\u00edsima Concepci\u00f3n, Av. Alonso de Ribera 2850, Concepci\u00f3n 4090541, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0517-8209","authenticated-orcid":false,"given":"Juan Francisco","family":"Loro-Ferrer","sequence":"additional","affiliation":[{"name":"Departamento Ciencias Cl\u00ednicas, Universidad de Las Palmas de Gran Canaria (ULPGC), 35001 Las Palmas de Gran Canaria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025). Obesity and Overweight."},{"key":"ref_2","unstructured":"NCD Risk Factor Collaboration (2024). Worldwide trends in underweight and obesity from 1990 to 2022: A pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults. 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