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BI and GLP\u20101RAs can be administered separately or as fixed\u2010ratio combinations (FRCs) for daily use (degludec+liraglutide, IDegLira, glargine\u2010100\u2009+\u2009lixisenatide iGlarLixi) or weekly use (icodec+semaglutide, IcoSema). The currently available FRCs IDegLira and iGlarLixi differ in their respective BI as well as GLP\u20101RA components. Liraglutide predominantly stimulates glucose\u2010dependent endogenous insulin secretion in response to nutrient challenges. In contrast, the rapid\u2010acting lixisenatide primarily delays gastric emptying over a few hours post\u2010dosing with little or no impact on insulin secretion. IDegLira in DUAL studies and iGlarLixi in LixiLan studies appear to have equivalent lowering effects on HbA1c, although IDegLira achieves a greater reduction in body weight. The weekly FRC IcoSema is superior to weekly insulin icodec (COMBINE 1), to semaglutide (COMBINE 2), and non\u2010inferior to basal\u2010bolus insulin therapy (COMBINE 3). Comparison of IcoSema with glargine\u2010100 is ongoing (COMBINE 4). However, all FRCs are limited by the low GLP\u20101RA dose relative to the insulin delivered. Whenever higher GLP\u20101RA doses are required (i.e., in obese people), the option of separate dosing of BI and GLP\u20101RA with independent titration of each component should be considered.<\/jats:p>","DOI":"10.1111\/dom.16616","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T06:53:31Z","timestamp":1752821611000},"page":"14-25","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["An overview of randomized clinical trials of fixed\u2010ratio combinations of basal insulin plus\n                    <scp>GLP<\/scp>\n                    \u2010\n                    <scp>1RA<\/scp>\n                    (injectable therapy): Lessons for advancing therapy in people with type 2 diabetes"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4966-4003","authenticated-orcid":false,"given":"Geremia 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