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Obesogenic environments promote unhealthy behavior, making weight management challenging. Until recently, effective pharmacological treatments were lacking. The introduction of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) represents a major breakthrough in obesity care, with the potential to transform treatment strategies. Despite their efficacy, high costs (as of 2025) limit accessibility, particularly in low and middle-income regions, where parallel, unregulated use is emerging. Obesity remains under-recognized as a primary medical condition, especially in populations prone to metabolic complications, including metabolic dysfunction-associated steatotic liver disease (MASLD). Gastroenterology has historically underestimated the role of GLP-1 RAs in the past. Moving forward, the choice between GLP-1 therapy and bariatric endoscopy\/surgery will become a central research focus, with treatment failures in one modality already leading to crossover. GLP-1 RAs are expected to significantly impact obesity-related comorbidities, including hypertension, dyslipidaemia, type-2 diabetes, sleep apnea, MASLD and inflammatory bowel disease (IBD). An \u201cObesity First\u201d approach may reshape healthcare by addressing obesity as the primary topic cause for chronic disease. By 2035, the role of GLP-1 RAs as potential lifelong treatment will become clearer, with generic market expansion anticipated following patent expirations (China 2026; Europe 2031).<\/jats:p>","DOI":"10.1007\/s12664-025-01882-5","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T19:04:09Z","timestamp":1761678249000},"page":"15-19","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The \u2018Obesity First\u2019 approach: Redefining the future of healthcare"],"prefix":"10.1007","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6332-0365","authenticated-orcid":false,"given":"Chris J. 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