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In Cohort 1, insulin tregopil administered 10 to 20 minutes before a meal resulted in optimal postmeal exposure and demonstrated better postprandial glucose\u2010lowering effect (glucose area under concentration\u2010time curve [AUC]) compared to the 30\u2010minute group. In Cohort 2, insulin tregopil pharmacokinetic exposure (plasma AUC) showed a progressive increase through 4, 5, and 6 hours of between\u2010meal interval. The 6\u2010hour between\u2010meal interval resulted in better absorption of insulin tregopil in comparison to 4\u2010 and 5\u2010hour intervals. However, no significant differences were observed in pharmacodynamic parameters except for higher glucose AUC<jats:sub>0\u2010180min<\/jats:sub> in the insulin tregopil 4\u2010hour group during the afternoon meal as compared to the morning meal. In Cohort 3, a high\u2010fiber meal had the least impact on insulin tregopil absorption and resulted in the highest reduction in plasma glucose levels in the afternoon. A high\u2010fat meal reduced insulin tregopil absorption in the afternoon meal; however, pharmacodynamic response was not diminished significantly. Insulin tregopil has a rapid onset of action of approximately 10 minutes and, when administered 10 to 20 minutes before a meal, demonstrated up to 13% to 18% reduction in blood glucose levels compared to baseline. A 5\u2010hour between\u2010meal interval minimizes the impact of a meal on absorption of subsequent (afternoon) insulin tregopil dose, and the pharmacodynamic response of insulin tregopil is not altered by meal composition. Insulin tregopil was well tolerated in patients with type 2 diabetes mellitus.<\/jats:p>","DOI":"10.1002\/cpdd.730","type":"journal-article","created":{"date-parts":[[2019,8,8]],"date-time":"2019-08-08T06:08:28Z","timestamp":1565244508000},"page":"74-86","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Pharmacokinetics and Pharmacodynamics of Insulin Tregopil in Relation to Premeal Dosing Time, Between Meal Interval, and Meal Composition in Patients With Type 2 Diabetes Mellitus"],"prefix":"10.1002","volume":"9","author":[{"given":"Anand","family":"Khedkar","sequence":"first","affiliation":[{"name":"Employed at Biocon Research Ltd., during study conduct  Bengaluru Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold","family":"Lebovitz","sequence":"additional","affiliation":[{"name":"State University of New York Health Science Centre at Brooklyn  Brooklyn NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Fleming","sequence":"additional","affiliation":[{"name":"Kinexum  Harpers Ferry WV USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Cherrington","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinu","family":"Jose","sequence":"additional","affiliation":[{"name":"Employed at Biocon Research Ltd., during study conduct  Bengaluru Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep N.","family":"Athalye","sequence":"additional","affiliation":[{"name":"Biocon Research Ltd.  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