{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T18:35:45Z","timestamp":1780511745667,"version":"3.54.1"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,8,8]],"date-time":"2017-08-08T00:00:00Z","timestamp":1502150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Nevada INBRE (NIH)","award":["NIH GM103440"],"award-info":[{"award-number":["NIH GM103440"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>\n<jats:table-wrap position=\"anchor\">\n\n<jats:table frame=\"hsides\">\n<jats:col\/>\n<jats:tbody>\n<jats:tr>\n<jats:td>Preclinical Research<\/jats:td>\n<\/jats:tr>\n<\/jats:tbody>\n<\/jats:table>\n<\/jats:table-wrap><\/jats:p><jats:p>Mimetics of Glucagon\u2010like peptide 1 (GLP\u20101) represent a useful alternative or complementary treatment choice to insulin in the treatment of diabetes mellitus. The lack of hypoglycemia as a side effect when GLP\u20101 receptor agonists are used along with the tendency of these therapeutic agents to prevent or even reduce weight gain makes them valuable targets in therapy development. However, native GLP\u20101 and many of its early analogues have very short half\u2010lives, requiring repeated treatment to maintain therapeutic levels. As all current treatments are injected subcutaneously, a large focus has been made on trying to extend the half\u2010lives of GLP\u20101 analogues while retaining bioactivity. Most success in this regard has been achieved with the use of peptide\u2010protein fusions, which are not as well suited for oral administration. However, recent work focused on the development of non\u2010fusion peptides with increased half\u2010lives that may be more appropriate for oral administration. This minireview discusses the structural characteristics of past and present analogues as well as the recent work conducted toward developing novel GLP\u20101 receptor agonists. Drug Dev Res 78 : 292\u2013299, 2017. \u00a9 2017 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ddr.21404","type":"journal-article","created":{"date-parts":[[2017,8,8]],"date-time":"2017-08-08T01:02:15Z","timestamp":1502154135000},"page":"292-299","source":"Crossref","is-referenced-by-count":28,"title":["Recent Advances in GLP\u20101 Receptor Agonists for Use in Diabetes Mellitus"],"prefix":"10.1002","volume":"78","author":[{"given":"Dominic N.","family":"McBrayer","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Nevada Reno Reno Nevada 89557"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yftah","family":"Tal\u2010Gan","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Nevada Reno Reno Nevada 89557"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,8]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.02.010"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.01.017"},{"key":"e_1_2_6_4_1","first-page":"483","article-title":"Gateways to clinical trials \u2010 July\/August 2003","volume":"25","author":"Bayes M","year":"2003","journal-title":"Methods Findings Exp Clin Pharmacol"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.50.070181.002125"},{"key":"e_1_2_6_6_1","first-page":"S379","article-title":"Superagonistic mechanism of increased glucodynamic and weight loss effects of (LAPS)CA\u2010Exendin\u20104 (efpeglenatide)","volume":"58","author":"Choi I","year":"2015","journal-title":"Diabetologia"},{"key":"e_1_2_6_7_1","volume-title":"A long\u2010acting Exendin\u20104 analog conjugate to the human Fc fragment reveals low immunogenic potential","author":"Choi IY","year":"2014"},{"key":"e_1_2_6_8_1","volume-title":"Underlying superagonistic mechanisms of efpeglenatide in glycaemic control and weight loss potency","author":"Choi IY","year":"2016"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-010-0102-x"},{"key":"e_1_2_6_10_1","first-page":"503","article-title":"Lixisenatide, a novel GLP\u20101 receptor agonist for the treatment of type 2 diabetes mellitus","volume":"12","author":"Christensen M","year":"2009","journal-title":"Idrugs"},{"key":"e_1_2_6_11_1","volume-title":"Safety, pharmacokinetics, and pharmacodynamics of a single subcutaneous dose of VRS\u2010859 in patients with type 2 diabetes","author":"Cleland JL","year":"2012"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69705-5"},{"key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"7402","DOI":"10.1016\/S0021-9258(18)42531-8","article-title":"Isolation and characterization of Exendin\u20104, an Exendin\u20103 analog, from heloderma\u2010suspectum venom \u2010 further evidence for an exendin receptor on dispersed acini from guinea\u2010pig pancreas","volume":"267","author":"Eng J","year":"1992","journal-title":"J Biol Chem"},{"key":"e_1_2_6_14_1","first-page":"A109","article-title":"Dose\u2010response for 28\u2010day glycemic improvement following a single injection of long\u2010acting\u2010release exenatide (Synthetic exendin\u20104) in diabetic fatty Zucker (ZDF) rats","volume":"52","author":"Gedulin B","year":"2003","journal-title":"Diabetes"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm4017448"},{"key":"e_1_2_6_16_1","first-page":"790","article-title":"Dulaglutide, a long\u2010acting GLP\u20101 analog fused with an Fc antibody fragment for the potential treatment of type 2 diabetes","volume":"12","author":"Jimenez\u2010Solem E","year":"2010","journal-title":"Curr Opin Mol Therapeut"},{"key":"e_1_2_6_17_1","unstructured":"JungS LimCK SongDH BaeSM KimYH KwonSC LeeGS.Hanmi Science Co. Ltd assignee.2016. 2016\/08\/23\/. N\u2010terminal modified exendin\u20104 patent. US9422349 B2."},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2012.01.036"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.3.751"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.108.000604"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85004"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2011.11.028"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.18.5485"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728214.2011.616493"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2014.03.005"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/00970002042006005"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-016-0180-0"},{"key":"e_1_2_6_28_1","volume-title":"Significant effects of HM11260C (efpeglenatide) on body weight over 20 weeks in obese subjects without diabetes: a randomized, double\u2010blind, placebo controlled study","author":"Pratley RE","year":"2015"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1588"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-1459"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-015-0279-z"},{"key":"e_1_2_6_32_1","unstructured":"SongDH LimCK KimYH KwonSC LeeGS BaeSM JungSY Hanmi Science Co. Ltd. assignee.2009. Insulinotropic peptide derivative wherein its n\u2010terminal amino acid is modified patent. CA2789123 A1."},{"key":"e_1_2_6_33_1","first-page":"A154","article-title":"Pharmacodynamics, pharmacokinetics, safety, and tolerability of albiglutide (Syncria (R)), a long\u2010acting GLP\u20101 mimetic, in subjects with type 2 diabetes","volume":"57","author":"Stewart MW","year":"2008","journal-title":"Diabetes"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12615"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2016.04.016"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.10.028"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2011.04.006"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2016.1123249"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201600374"},{"key":"e_1_2_6_40_1","volume-title":"LAPS CA\u2010exendin\u20104 (efpeglenatide) enhances insulin secretion and beta cell responsiveness in subjects with type 2 diabetes","author":"Watkins E","year":"2015"},{"key":"e_1_2_6_41_1","unstructured":"WieczorekB SpetzlerJ KruseT LinderothL KofoedJ.Novo Nordisk A\/S (Bagsvaerd DK) assignee.2017. Double\u2010Acylated GLP\u20101 Derivatives patent United States Patent Application. 20170058014 Kind Code: A1."},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2015.11.008"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1513004112"},{"key":"e_1_2_6_44_1","volume-title":"Once weekly HM11260C (efpeglenatide) significantly improves glycemic control and reduced body weight in patients with type 2 diabetes: a phase II dose finding study","author":"Yoon K\u2010H","year":"2015"}],"container-title":["Drug Development Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fddr.21404","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.21404","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T15:43:46Z","timestamp":1760370226000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/ddr.21404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,8]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["10.1002\/ddr.21404"],"URL":"https:\/\/doi.org\/10.1002\/ddr.21404","archive":["Portico"],"relation":{},"ISSN":["0272-4391","1098-2299"],"issn-type":[{"value":"0272-4391","type":"print"},{"value":"1098-2299","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,8]]}}}