{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:36:37Z","timestamp":1793144197230,"version":"4.5.0"},"reference-count":110,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Obesity is a chronic, heterogeneous disease with marked interindividual variability in response to anti-obesity medications. Although GLP-1 receptor agonists (GLP-1RAs) and dual incretin agonists produce substantial average weight loss in clinical trials, real-world effectiveness is limited by interindividual variability, gastrointestinal intolerance, incomplete dose escalation, cost and access barriers, poor long-term persistence, and weight plateau or regain in a subset of treated patients. Weight regain is particularly consistent after treatment discontinuation, reinforcing the chronic-care nature of obesity pharmacotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To synthesize evidence on phenotypic and genomic determinants of variability in pharmacotherapy response and propose a pragmatic framework for precision pharmacotherapy in obesity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Narrative review integrating data from randomized trials,\n                      <jats:italic>post-hoc<\/jats:italic>\n                      subgroup analyses, observational cohorts, neurobehavioral studies, pharmacogenomic investigations, and polygenic risk score research addressing predictors of efficacy and tolerability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Response heterogeneity reflects interactions among central satiety and reward circuitry, baseline metabolic and glycemic status, sex, baseline adiposity, treatment indication, previous GLP-1RA exposure, adherence, and tolerability. Early on-treatment weight change, usually assessed within 12\u201316\u202fweeks and in some liraglutide studies as early as 1\u202fmonth, is the most clinically actionable predictor of longer-term outcomes. Phenotype-guided approaches that classify dominant mechanisms such as impaired satiation, postprandial hunger, emotional or hedonic eating, and low energy expenditure offer a feasible bridge between pathophysiology and medication selection. Emerging genomic signals are promising but remain insufficiently replicated for routine clinical use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Precision pharmacotherapy in obesity is most viable today through phenotype-guided treatment, structured early-response monitoring, and proactive management of adherence and tolerability. Genomic tools may eventually refine treatment selection, but they remain investigational and require prospective, multi-ancestry validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1803474","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T11:10:33Z","timestamp":1783336233000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Phenotypic and genomic frameworks for precision pharmacotherapy in obesity: a narrative review"],"prefix":"10.3389","volume":"13","author":[{"given":"Dario S.","family":"Lopez Delgado","sequence":"first","affiliation":[{"name":"Fundaci\u00f3n Hospital San Pedro","place":["Pasto, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam Gabriela","family":"Reyes-Zerme\u00f1o","sequence":"additional","affiliation":[{"name":"Servicio de Gastroenterolog\u00eda, Centro M\u00e9dico Nacional 20 de Noviembre, ISSSTE","place":["Ciudad de M\u00e9xico, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elian David Sanjuanelo","family":"Lemus","sequence":"additional","affiliation":[{"name":"School of Medicine, Universidad del Norte","place":["Barranquilla, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine G.","family":"Acosta-Celis","sequence":"additional","affiliation":[{"name":"Department of Research, Tau Clinical Research Network","place":["Chiclayo, Peru"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Amparo","family":"Kant\u00fan-Mar\u00edn","sequence":"additional","affiliation":[{"name":"Department of Nursing, Universidad Aut\u00f3noma del Carmen","place":["Ciudad del Carmen, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mart\u00edn","family":"Gomez-Lujan","sequence":"additional","affiliation":[{"name":"School of Medicine, Universidad Nacional Federico Villarreal","place":["Lima, Peru"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin Gabriel","family":"Fallaza-Moya","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas (IIBISMED)","place":["Cochabamba, Bolivia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Mu\u00f1oz-Chuquil\u00edn","sequence":"additional","affiliation":[{"name":"Unidad de Postgrado, Universidad Nacional de Trujillo","place":["Trujillo, Peru"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Trujillo-Levano","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Carrera de Medicina Humana, Universidad Cient\u00edfica del Sur","place":["Lima, Peru"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Gutierrez-Chavez","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Universidad Continental","place":["Cusco, Peru"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Bonilla-Asalde","sequence":"additional","affiliation":[{"name":"Vice-Rectorate for Research, Universidad Se\u00f1or de Sip\u00e1n","place":["Chiclayo, Peru"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriana","family":"Rivera-Lozada","sequence":"additional","affiliation":[{"name":"Vice-Rectorate for Research, Universidad Se\u00f1or de Sip\u00e1n","place":["Chiclayo, Peru"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshuan J.","family":"Barboza","sequence":"additional","affiliation":[{"name":"Vice-Rectorate for Research, Universidad Se\u00f1or de Sip\u00e1n","place":["Chiclayo, 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