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Their development emerged from the understanding that a combined islet dysfunction comprising of impaired insulin secretion and exaggerated glucagon secretion is the key defect of hyperglycemia. <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101 was shown to target these defects, and after the discovery that dipeptidyl peptidase\u20104 inactivates native <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101, several different dipeptidyl peptidase\u20104\u2010resistant <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101 receptor agonists have been developed. They are administered subcutaneously, but show differences in molecular structure, molecular size and pharmacokinetics, the latter allowing twice\u2010daily, once\u2010daily or once\u2010weekly administration. They have been shown to be efficient in reducing both glycated hemoglobin and bodyweight, and to be safe and highly tolerable. Cardiovascular outcomes trials have shown them to be neutral or beneficial. <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101 receptor agonists are positioned as add\u2010ons to metformin alone or in combination with oral agents in the clinical paradigm. They are also efficient when combined with insulin, and fixed dose combinations with long\u2010acting insulin have been developed. Recent development includes a very long administration schedule and oral availability. The research from the first demonstration of the antidiabetic action of <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101 in the early 1990s to the enormously accumulated data today represents a successful and rational development, which has been characterized by focused perseverance to establish this therapy in the management of type 2 diabetes.<\/jats:p>","DOI":"10.1111\/jdi.12911","type":"journal-article","created":{"date-parts":[[2018,8,12]],"date-time":"2018-08-12T11:08:14Z","timestamp":1534072094000},"page":"196-201","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Glucagon\u2010like peptide\u20101 receptor agonists for type 2 diabetes: A rational drug development"],"prefix":"10.1111","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9804-5340","authenticated-orcid":false,"given":"Bo","family":"Ahr\u00e9n","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences Lund Lund University Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,17]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.40.2.166"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1212166"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-5-3-395"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.25.2.136"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2006-0026"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2015.03.011"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/db08-1158"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/302716a0"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2782"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-381517-0.00007-2"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69705-5"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)91194-9"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-123-4-2009"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006676-199103000-00013"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.10.2860"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.03.054"},{"key":"e_1_2_14_18_1","first-page":"A73","article-title":"Glucagon\u2010like insulinotropic peptide 1 (7\u201036) \u2010 new approach to treating diabetes? 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