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While DPP-4 inhibitors offer modest glycaemic benefits, GLP1RAs such as liraglutide and semaglutide have demonstrated significant weight loss and cardiometabolic protection. Dual GIP\/GLP-1 agonist tirzepatide and triple agonist retatrutide have shown unprecedented efficacy, with up to 24% body weight reduction and improvement in hepatic and inflammatory markers. Agents like cotadutide and efinopegdutide further expand indications to MASLD and metabolic dysfunction associated steatohepatitis (MASH). Despite promising outcomes, challenges persist in terms of cost, accessibility, and the underrepresentation of low- and middle-income countries in major trials. Pharmacogenomic variability may also influence therapeutic response. Incretin-based multi-agonists offer a transformative, multi-system approach to metabolic disease but require tailored implementation. This review provides an updated synthesis of therapeutic developments and outlines priorities for future research, regulatory policy, and equitable global integration as incretin-based therapies have evolved into a versatile class addressing glycaemic control, weight loss, and cardio-metabolic risk.<\/jats:p>","DOI":"10.25259\/ijmr_2041_2025","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T07:08:28Z","timestamp":1777360108000},"page":"427-435","update-policy":"https:\/\/doi.org\/10.25259\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evolution of incretin-based therapies: From GLP-1 monotherapy to dual and triple agonists: A new era in metabolic therapy"],"prefix":"10.25259","volume":"163","author":[{"given":"Monika","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Moti Lal Nehru Medical College, Prayagraj, Uttar Pradesh, 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