{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:59:45Z","timestamp":1790373585931,"version":"4.1.0"},"reference-count":64,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp; Metabol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Conventional single\u2010agent drugs yield modest, plateauing weight loss and often lead to weight regain. Combination pharmacotherapy is a logical next step to target complementary pathways of weight control while reducing toxicity and treatment burden. This review synthesises mechanisms and clinical evidence for fixed\u2010dose combinations, multi\u2010agonist peptides, add\u2010on regimens and multimodal strategies integrating pharmacotherapy with procedures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a narrative review of clinical trials and observational studies on approved and emerging obesity pharmacotherapy combinations, focusing on mechanistic complementarity, efficacy, safety and practical implementation. Agents were mapped to three domains of energy homeostasis\u2014homeostatic appetite regulation, hedonic\u2010reward circuitry and peripheral metabolic effector pathways\u2014to inform interpretation of combination strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fixed\u2010dose combinations such as phentermine\u2010topiramate and naltrexone\u2010bupropion yield greater weight loss than their individual components but also carry gastrointestinal, cardiovascular and neuropsychiatric risks. Multi\u2010agonist peptides integrating GLP\u20101, GIP, glucagon, or amylin deliver double\u2010digit weight loss and improve glycemic and cardiometabolic profiles, but increase the risk of gastrointestinal adverse events, requiring close monitoring. Add\u2010on regimens that combine GLP\u20101 agonists with approved obesity medications or SGLT\u20102 inhibitors, and multimodal strategies that pair drugs with bariatric or endoscopic procedures, generally show additive rather than truly synergistic effects on weight loss.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Available data suggest that combination pharmacotherapy can extend current approaches to precision obesity care, generally providing additive benefits alongside increased regimen complexity, costs and adverse\u2010event risks. Thoughtful, phenotype\u2010guided selection and comparative studies versus potent monotherapies, enriched by multi\u2010omics and behavioural insights, may clarify which patients benefit most and sustainably from these strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/edm2.70307","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:09:22Z","timestamp":1786511362000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combination Pharmacotherapies for Obesity\u2014Current Evidence and Future Directions"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5681-6522","authenticated-orcid":false,"given":"A. B. 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