GLP-1 receptor agonists: Difference between revisions

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The medicines that followed traced a striking expansion of use. [[Exenatide]] and the early agents required injection once or twice daily; later molecules were engineered for far longer action. [[Liraglutide]] was approved for type 2 diabetes in 2010 and, at a higher dose, for obesity in 2014. [[Dulaglutide]], a once-weekly agent, followed in 2014. [[Semaglutide]] was approved in 2017, later also in an oral form, and [[tirzepatide]] — which acts on a second gut-hormone receptor (GIP) as well as the GLP-1 receptor — was approved in 2022.<ref name="hist-glp1"/>

The expansion was driven by a long series of large clinical trials, and it ran in a consistent direction: from blood-sugar control, to weight loss, to the prevention of cardiovascular and kidney disease. Trials reported substantial weight reduction with the newer agents; cardiovascular outcome trials reported reductions in cardiovascular events, including — in the SELECT trial — a roughly twenty per cent reduction in major adverse cardiovascular events with [[semaglutide]] in people with obesity but without diabetes;<ref name="select">Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. ''N Engl J Med.'' 2023;389(24):2221–2232. PMID 37952131.</ref> and further trials examined kidney outcomes and other conditions. Head-to-head trials have compared agents directly, with [[tirzepatide]] generally producing greater average weight loss than [[semaglutide]].<ref name="surmount5">Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. ''N Engl J Med.'' 2025;393(1):26–36. PMID 40353578.</ref> This steady widening of approved uses — sometimes described as ~~indication~~ expansion — is the defining feature of the class's short history, and the reason these medicines moved within two decades from a niche diabetes treatment to a central place in medicine and in public attention.

The expansion was driven by a long series of large clinical trials, and it ran in a consistent direction: from blood-sugar control, to weight loss, to the prevention of cardiovascular and kidney disease. Trials reported substantial weight reduction with the newer agents; cardiovascular outcome trials reported reductions in cardiovascular events, including — in the SELECT trial — a roughly twenty per cent reduction in major adverse cardiovascular events with [[semaglutide]] in people with obesity but without diabetes;<ref name="select">Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. ''N Engl J Med.'' 2023;389(24):2221–2232. PMID 37952131.</ref> and further trials examined kidney outcomes and other conditions. Head-to-head trials have compared agents directly, with [[tirzepatide]] generally producing greater average weight loss than [[semaglutide]].<ref name="surmount5">Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. ''N Engl J Med.'' 2025;393(1):26–36. PMID 40353578.</ref> This steady widening of approved uses — sometimes described as problem expansion — is the defining feature of the class's short history, and the reason these medicines moved within two decades from a niche diabetes treatment to a central place in medicine and in public attention.

== Mechanisms ==

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