{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:25:53Z","timestamp":1788326753622,"version":"build-2803163510"},"reference-count":19,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This trial evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of oral insulin Tregopil (Part 1; results discussed in this paper) and the post\u2010prandial glucose control with different meal types in comparison with insulin aspart (Part 2) in patients with type 1 diabetes mellitus (T1DM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>This Phase 1, open\u2010label, multiple ascending dose (30\/45\/60\u2009mg\/60\u2009+\u200930\u2009mg rescue insulin Tregopil) trial enrolled 37 patients with T1DM (3 female [8.1%], 34 male [91.9%]; median age: 39.5\u2009years). Following screening, patients entered a run\u2010in phase to optimize their basal\u2010bolus (insulin glargine and insulin aspart) insulin therapy, and insulin Tregopil was administered orally 10\u2009min before the three major meals of the day in all cohorts during this period. Safety assessments included adverse events and hypo\u2212\/hyperglycaemic episodes, vital signs, electrocardiograms, laboratory safety parameters and physical examination. PK and PD were the secondary objectives.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The overall safety profile of insulin Tregopil indicated no safety concerns except a PD effect (hypoglycaemia). The incidence of hypoglycaemia did not increase with increasing doses of insulin Tregopil, and none of the episodes were severe. In general, the variability of the PK\/PD parameters was high. Insulin Tregopil demonstrated a rapid onset of action, with peak blood concentrations reached within 15\u201320\u2009min post\u2010dosing. Subsequently, insulin Tregopil exerted a PD effect for up to 105\u2009min.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Fixed\u2010dose insulin Tregopil reduced the requirement for insulin aspart supplementation, although it was not a viable stand\u2010alone option for the daily management of T1DM. Insulin Tregopil could be explored with a flexible dosing approach and be titrated based on individual needs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>The trial is registered at Clinicaltrials.gov (CT.gov identifier: NCT04141423). The ethical approval number for the protocol is 2019146.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.16327","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T01:01:36Z","timestamp":1744333296000},"page":"3154-3164","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An open\u2010label, multiple ascending dose trial of orally administered insulin Tregopil in patients with type 1 diabetes mellitus to evaluate its pharmacokinetics, pharmacodynamics, safety and tolerability"],"prefix":"10.1111","volume":"27","author":[{"given":"Esther","family":"Latres","sequence":"first","affiliation":[{"name":"Breakthrough T1D (formerly JDRF International)  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leona","family":"Plum\u2010Moerschel","sequence":"additional","affiliation":[{"name":"Profil  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sundara Moorthi Nainar","family":"Murugesan","sequence":"additional","affiliation":[{"name":"Biocon Biologics Limited  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Lou","sequence":"additional","affiliation":[{"name":"Breakthrough T1D (formerly JDRF International)  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayanti","family":"Panda","sequence":"additional","affiliation":[{"name":"Biocon Biologics Limited  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwani","family":"Marwah","sequence":"additional","affiliation":[{"name":"Biocon Biologics Limited  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Samsonraj","sequence":"additional","affiliation":[{"name":"Biocon Biologics Limited  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. L.","family":"Gopu","sequence":"additional","affiliation":[{"name":"Biocon Biologics Limited  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7186-0049","authenticated-orcid":false,"given":"Subramanian","family":"Loganathan","sequence":"additional","affiliation":[{"name":"Biocon Biologics Limited  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep Nilkanth","family":"Athalye","sequence":"additional","affiliation":[{"name":"Biocon Biologics Limited  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"DiGiacintoJ HigueraV.Everything you need to know about insulin.2023https:\/\/www.healthline.com\/health\/type\u20102\u2010diabetes\/insulin#takeaway. Accessed October 21 2024"},{"key":"e_1_2_11_3_1","unstructured":"International Diabetes Federation.Type 1 diabetes 2023.https:\/\/www.idf.org\/aboutdiabetes\/type-1-diabetes.html. Accessed October 21 2024"},{"key":"e_1_2_11_4_1","unstructured":"International Diabetes Federation.Facts & figures 2023.https:\/\/www.idf.org\/aboutdiabetes\/what-is-diabetes\/facts-figures.html. Accessed October 21 2024"},{"key":"e_1_2_11_5_1","unstructured":"WexlerDJ.Patient education: Type 2 diabetes: Insulin treatment (Beyond the Basics). 2023https:\/\/www.uptodate.com\/contents\/type-2-diabetes-insulin-treatment-beyond-the-basics\/print. Accessed October 21 2024"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-019-00743-7"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/cd18-0076"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13098-021-00700-0"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40744-020-00245-0"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-023-01925-1"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13498"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.730"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2010.01213.x"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2022.2141569"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc24-0838"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-018-0696-8"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-801238-3.97984-4"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2009.01153.x"},{"issue":"1","key":"e_1_2_11_19_1","first-page":"521","article-title":"Oral insulin: type I diabetes (T1DM) patient response upon preprandial administration","volume":"59","author":"Eldor R","year":"2010","journal-title":"Diabetes"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-019-00772-2"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.16327","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T06:55:36Z","timestamp":1761893736000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.16327"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,10]]},"references-count":19,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/dom.16327"],"URL":"https:\/\/doi.org\/10.1111\/dom.16327","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/DOM.16327\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16327\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16327\/v1\/review4","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16327\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16327\/v1\/review5","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16327\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16327\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16327\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16327\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.16327\/v1\/review1","asserted-by":"object"}]},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,10]]},"assertion":[{"value":"2024-12-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}