{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T12:05:54Z","timestamp":1792325154128,"version":"4.4.0"},"reference-count":30,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2014,2,27]],"date-time":"2014-02-27T00:00:00Z","timestamp":1393459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Diabetes Sci Technol"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The dose response of postprandial plasma glucose (PPG) to add-on, premeal oral hepatic-directed vesicle-insulin (HDV-I), an investigational lipid bio-nanoparticle hepatocyte-targeted insulin delivery system, was evaluated in a 3-test-meal\/day model in type 2 diabetes patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method:<\/jats:title>\n                    <jats:p>\n                      The single-blind, placebo-controlled, dose-escalating trial enrolled 6 patients with HbA\n                      <jats:sub>1c<\/jats:sub>\n                      8.6 \u00b1 2.0% (70.0 \u00b1 21.9 mmol\/mol) and on stable metformin therapy. Patients received oral HDV-I capsules daily 30 minutes before breakfast, lunch, and dinner as follows: placebo capsules, 0.05, 0.1, 0.2, and 0.4 U\/kg on days 1, 2, 3, 4, and 5, respectively. Outcome measures were PPG and incremental PPG area under the concentration-time curve (AUC).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>All 4 doses of oral HDV-I statistically significantly lowered mean PPG ( P \u2264 .0110 each) and incremental PPG ( P \u2264 .0352 each) AUC compared to placebo. A linear dose response was not observed. The 0.05 U\/kg dose was the minimum effective dose in the dosage range studied. Three adverse events unrelated to treatment were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Add-on oral HDV-I 0.05-0.4 U\/kg significantly lowered PPG excursions and the dose response curve was flat. These results are consistent with the lack of a linear dose response between portal and systemic plasma insulin concentrations in previous animal and human studies. Oral HDV-I was safe and well tolerated.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1932296814524871","type":"journal-article","created":{"date-parts":[[2014,2,27]],"date-time":"2014-02-27T21:51:13Z","timestamp":1393537873000},"page":"551-559","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":35,"title":["A Single-blind, Placebo-controlled, Dose-ranging Trial of Oral Hepatic-directed Vesicle Insulin Add-on to Oral Antidiabetic Treatment in Patients With Type 2 Diabetes Mellitus"],"prefix":"10.1177","volume":"8","author":[{"given":"W. 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