{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:18:42Z","timestamp":1791897522419,"version":"4.3.4"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,10,24]],"date-time":"2021-10-24T00:00:00Z","timestamp":1635033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To compare the pharmacokinetics (PK), glucodynamics (GD), and tolerability following single and multiple daily subcutaneous (SC) doses of ultra rapid lispro (URLi) and Humalog\u00ae in patients with type 1 diabetes mellitus (T1D).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>This was a two\u2010part, randomized, double\u2010blind, Phase 1b study. Part A used a six\u2010period crossover design to assess PK and GD response to a solid mixed meal tolerance test (MMTT) following a single dose of URLi or Humalog administered 15\u2009min before, immediately before, and 15\u2009min after the start of the meal. Part B evaluated URLi or Humalog during 2\u2009weeks of multiple daily dosing with a parallel design. The PK and GD were assessed following MMTTs at the beginning and end of the 2\u2010week period when insulins were administered immediately before the start of the meal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>URLi increased the insulin exposure within the first 30 min postdose by 2.2\u2010fold and reduced the time to early half\u2010maximal drug concentration by 37% compared with Humalog. Overall, URLi resulted in better postprandial glucose lowering when dosed before, immediately before, or after a meal compared with Humalog. Comparing the same meal\u2010to\u2010dose timing between the insulins, postprandial glucose excursion over 5\u00a0hours was reduced by 40%\u201044% for all three dose timings (\u221215, 0, and +15\u2009min) with URLi, achieving statistical significance for the 0\u2010 and +15\u2010min timings. The PK and GD profiles were sustained after daily SC dosing for 2\u2009weeks in patients with T1D. The number of documented hypoglycaemic events was similar between URLi and Humalog during the postprandial period of the MMTTs and the outpatient period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>URLi showed accelerated insulin lispro absorption and greater postprandial glucose reduction at different meal\u2010to\u2010dose timings compared with Humalog and was well tolerated in patients with T1D.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14563","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T22:52:09Z","timestamp":1633042329000},"page":"196-203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Ultra rapid lispro (URLi) shows accelerated pharmacokinetics and greater reduction in postprandial glucose versus\n                    <scp>Humalog\u00ae<\/scp>\n                    in patients with type 1 diabetes mellitus in a randomized, double\u2010blind meal test early\u2010phase study"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2538-2573","authenticated-orcid":false,"given":"Christof","family":"Kazda","sequence":"first","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5434-7905","authenticated-orcid":false,"given":"Jennifer","family":"Leohr","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Liu","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shobha","family":"Reddy","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Anne","family":"Dellva","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei Teng","family":"Loh","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hardy","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leona","family":"Plum\u2010M\u00f6rschel","sequence":"additional","affiliation":[{"name":"Profil  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-S008"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/diaclin.20.1.11"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/193229681200600402"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9136(199607)13:7<625::AID-DIA134>3.0.CO;2-2"},{"key":"e_1_2_9_6_1","unstructured":"Humalog\u00ae [package insert]. Indianapolis IN: Eli Lilly and Company; 2017."},{"key":"e_1_2_9_7_1","unstructured":"Remodulin [package insert for US]. Research Triangle Park NC: United Therapeutics Corp; 2014."},{"issue":"1","key":"e_1_2_9_8_1","first-page":"A253","article-title":"Treprostinil causes local vasodilation, is well tolerated, and results in faster absorption of insulin lispro","volume":"66","author":"Pratt E","year":"2017","journal-title":"Diabetes."},{"issue":"1","key":"e_1_2_9_9_1","first-page":"A250","article-title":"Exploration of the mechanism of accelerated absorption for a novel insulin lispro formulation","volume":"66","author":"Michael MD","year":"2017","journal-title":"Diabetes"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00903-0"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00901-2"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14100"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc19-2550"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1932296821991216"},{"key":"e_1_2_9_15_1","first-page":"88","volume-title":"Design and Analysis of Bioavailability and Bioequivalence Studies","author":"Chow S","year":"2009"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-2643"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.14563","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.14563","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.14563","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T06:12:33Z","timestamp":1761891153000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.14563"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,24]]},"references-count":15,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["10.1111\/dom.14563"],"URL":"https:\/\/doi.org\/10.1111\/dom.14563","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,24]]},"assertion":[{"value":"2021-04-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}