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Incretin
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<h2 id="medical-uses">Medical uses</h2> <p><a href="/facts/Medication/h9mhwWP2">Medications</a> based on incretins are used in the treatment of <a href="/facts/Type_2_diabetes_mellitus/zCMXksmt">type 2 diabetes mellitus</a> as well as the management of <a href="/facts/Obesity/RBF9y5Vl">obesity</a>. </p><p>Most of the earliest incretin-targeting agents to be approved fell into the class of <a href="/facts/DPP-4_inhibitors/uqBmECL0">DPP-4 inhibitors</a>; these inhibit <a href="/facts/Dipeptidyl_peptidase-4/8CchtyzM">DPP-4</a> and thus prevent the enzymatic degradation of GLP-1 and GIP. The first medication in this class, <a href="/facts/Sitagliptin/KY8oN8zM">sitagliptin</a>, received FDA approval in 2006 for the treatment of type 2 diabetes mellitus. </p><p>The <a href="/facts/Glucagon-like_peptide-1_receptor_agonist/ruP4tEJC">GLP-1 analogs</a> principally act as agonists of the GLP-1 receptor and are thus insulinotropic. <a href="/facts/Exenatide/LPa5uUqW">Exenatide</a> was the first drug in this class to be used in the treatment of type 2 diabetes; it first received FDA approval in 2005. More recently, longer-acting and more potent GLP-1 analogs have been developed, most notably <a href="/facts/Semaglutide/g565XV32">semaglutide</a>, which received FDA approval for the treatment of type 2 diabetes in 2017. It was subsequently approved for the management of <a href="/facts/Obesity/RBF9y5Vl">obesity</a>. In 2021, it was in the Top 100 most-prescribed drugs in the United States. </p><p><a href="/facts/Tirzepatide/7LQNoMgR">Tirzepatide</a> (Mounjaro) is a potent <a href="/facts/Gastric_inhibitory_polypeptide/VyhleUdR">GIP</a> analog with agonist activity at GIP and GLP-1 receptors. It was approved for the treatment of type 2 diabetes in the United States in May 2022, and for the management of obesity in November 2023. </p> <h2 id="incretin-effect">Incretin effect</h2> <p>The incretin effect describes the phenomenon whereby oral glucose intake elicits a higher insulin response compared to intravenously introduced glucose that produces the same levels of serum glucose levels.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> </p> <h2 id="history">History</h2> <p>In 1932, <a href="/facts/Belgians/xSmHFHch">Belgian</a> <a href="/facts/Physiologist/fh25y2pQ">physiologist</a> Jean La Barre used the word "incretin" for a <a href="/facts/Gastrointestinal_hormone/FM8hM78n">gut hormone</a> which stimulates the <a href="/facts/Pancreatic_islets/PJVtM7MY">endocrine pancreas</a> including <a href="/facts/Insulin/oXG0myt1">insulin</a> release.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> He also proposed that such incretins could be used as a treatment for diabetes mellitus.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Secretin_family/3EwgY2Sb">Secretin family</a></li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Nauck MA, Meier JJ (February 2018). "Incretin hormones: Their role in health and disease". Diabetes, Obesity & Metabolism. 20 (Suppl 1): 5–21. doi:10.1111/dom.13129. PMID 29364588. <a href="https://doi.org/10.1111%2Fdom.13129" target="_blank">https://doi.org/10.1111%2Fdom.13129</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Nauck MA, Meier JJ (February 2018). "Incretin hormones: Their role in health and disease". Diabetes, Obesity & Metabolism. 20 (Suppl 1): 5–21. doi:10.1111/dom.13129. PMID 29364588. <a href="https://doi.org/10.1111%2Fdom.13129" target="_blank">https://doi.org/10.1111%2Fdom.13129</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Jorsal T, Rhee NA, Pedersen J, Wahlgren CD, Mortensen B, Jepsen SL, Jelsing J, Dalbøge LS, Vilmann P, Hassan H, Hendel JW, Poulsen SS, Holst JJ, Vilsbøll T, Knop FK (February 2018). "Enteroendocrine K and L cells in healthy and type 2 diabetic individuals". Diabetologia. 61 (2): 284–294. doi:10.1007/s00125-017-4450-9. PMID 28956082. <a href="https://doi.org/10.1007%2Fs00125-017-4450-9" target="_blank">https://doi.org/10.1007%2Fs00125-017-4450-9</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Iwasaki K, Harada N, Sasaki K, Yamane S, Iida K, Suzuki K, Hamasaki A, Nasteska D, Shibue K, Joo E, Harada T, Hashimoto T, Asakawa Y, Hirasawa A, Inagaki N (March 2015). "Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K cells of the upper small intestine and has a critical role in GIP secretion after fat ingestion". Endocrinology. 156 (3): 837–46. doi:10.1210/en.2014-1653. hdl:2433/215430. PMID 25535828. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Kim YA, Keogh JB, Clifton PM (June 2018). "Probiotics, prebiotics, synbiotics and insulin sensitivity". Nutrition Research Reviews. 31 (1): 35–51. doi:10.1017/S095442241700018X. PMID 29037268. <a href="https://doi.org/10.1017%2FS095442241700018X" target="_blank">https://doi.org/10.1017%2FS095442241700018X</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Drucker DJ, Nauck MA (November 2006). "The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes". Lancet. 368 (9548): 1696–705. doi:10.1016/S0140-6736(06)69705-5. PMID 17098089. S2CID 25748028. <a href="/wiki/Daniel_J._Drucker" target="_blank">/wiki/Daniel_J._Drucker</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Amori RE, Lau J, Pittas AG (July 2007). "Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis". JAMA. 298 (2): 194–206. doi:10.1001/jama.298.2.194. PMID 17622601. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Rang HP, Ritter JM, Flower R, Henderson G (2016). Rang and Dale's Pharmacology (8th ed.). United Kingdom: Elsevier Churchill Livingstone. p. 385. ISBN 9780702053627. OCLC 903083639. <a href="9780702053627" target="_blank">9780702053627</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Nauck, Michael A; Meier, Juris J (June 2016). "The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions". The Lancet Diabetes & Endocrinology. 4 (6): 525–536. doi:10.1016/s2213-8587(15)00482-9. ISSN 2213-8587. PMID 26876794. <a href="https://doi.org/10.1016/S2213-8587(15)00482-9" target="_blank">https://doi.org/10.1016/S2213-8587(15)00482-9</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Rehfeld JF (2018-07-16). "The Origin and Understanding of the Incretin Concept". Frontiers in Endocrinology. 9: 387. doi:10.3389/fendo.2018.00387. PMC 6054964. PMID 30061863. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054964" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054964</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Rehfeld JF (2018-07-16). "The Origin and Understanding of the Incretin Concept". Frontiers in Endocrinology. 9: 387. doi:10.3389/fendo.2018.00387. PMC 6054964. PMID 30061863. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054964" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054964</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> </ol>