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The introduction of advanced pharmacotherapies, including GLP-1 receptor agonists (GLP-1 RA), dual Glucose-dependent Insulinotropic Polypeptide\/Glucagon-like Peptide-1 (GIP\/GLP-1) agonists, and emerging triple agonists, has facilitated a shift from weight-centric goals to precision-based obesity care. This review provides a clinical framework for pharmacologic treatment, organized by phenotype, obesity-related complications, age, and behavioral traits.<\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n Narrative review of randomized trials, meta-analyses, real-world evidence, and international guidelines through May 2025. Evidence was synthesized across key obesity phenotypes, cardiometabolic, hepatic, renal, mechanical, behavioral, and stratified by life stage, including pediatric, reproductive-age, and older adults, with attention to safety, cost-effectiveness, and special populations.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n In established Atherosclerotic Cardiovascular Disease, semaglutide significantly reduces major adverse cardiovascular events. Tirzepatide offers cardiometabolic benefits for high-risk people without overt disease. Both agents improve symptoms and function in Heart Failure with Preserved Ejection Fraction, irrespective of glycemia or weight loss. In Chronic Kidney Disease, they decrease albuminuria and eGFR decline. In Metabolic Dysfunction-Associated Steatotic Liver Disease, GLP-1 RAs and GIP\/GLP-1 RAs demonstrate marked histological improvements. Mechanical complications such as osteoarthritis and sleep apnea are improved by anti-obesity medications-induced weight loss. GLP-1 RAs and naltrexone\/bupropion prove effective against binge and emotional eating. In youths, liraglutide and semaglutide are both approved and effective. Liraglutide and orlistat preserve lean mass alongside resistance training and adequate protein intake in older and sarcopenic people.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n An anti-obesity treatment framework focused on both phenotype and complication burden improves the personalization of obesity care and supports clinical decision-making throughout a person\u2019s lifespan.<\/jats:p>\n <\/jats:sec>","DOI":"10.1007\/s40618-025-02700-7","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T07:21:19Z","timestamp":1762759279000},"page":"2761-2798","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan"],"prefix":"10.1007","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9139-7159","authenticated-orcid":false,"given":"Dario","family":"Tuccinardi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Masi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikiko","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Zanghi Buffi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"De Domenico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Berti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Cipriani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melania","family":"Manco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Manfrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uberto","family":"Pagotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"2700_CR1","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1111\/obr.12551","volume":"18","author":"GA Bray","year":"2017","unstructured":"Bray GA, Kim KK, Wilding JPH, World Obesity Federation (2017) Obesity: a chronic relapsing progressive disease process. 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UP is Editor in Chief of The Journal of Endocrinological Investigation. The manuscript will be handled by an independent editor. UP is a member of Advisory Boards of Novo Nordisk, Sciterion, Boehringer Ingelheim, Pfizer, Lilly Italia, Lilly Corporate and he received speaker fees from: Lilly Italia, Novo Nordisk, Astra-Zeneca, Bruno Farmaceutici, Rhythm Pharma, Merck, IQVIA; DT received funding for educational sessions from: Novo Nordisk, Eli Lilly, Boehringer-Ingelheim, Guidotti, Astra Zeneca, Sanofi and Bruno Farmaceutici; for institutional research grant support or funding for clinical trials from Novo Nordisk, Eli Lilly, Abbott, Boehringer-Ingelheim, Amgen, and Astra Zeneca; and Institutional Scientific Board and\/or consulting from Eli Lilly, Astra Zeneca, and Novo Nordisk. MW received funding for educational sessions from: Novo Nordisk, Eli Lilly, Theras Lifetech and Bruno Farmaceutici; and Institutional Scientific Board and\/or consulting from Eli Lilly, Theras Lifetech, and Novo Nordisk.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}