{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T23:55:04Z","timestamp":1789343704630,"version":"build-2803163510"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T00:00:00Z","timestamp":1668988800000},"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":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To assess the safety and efficacy of multiple daily doses of oral insulin (ORMD\u20100801) in subjects with type 2 diabetes (T2DM) over 12\u2009weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Participants with T2DM on metformin or combination oral therapy with glycated haemoglobin (HbA1c) levels \u2265\u20097.5% (58 mmol\/mol) were randomized to receive ORMD\u20100801 8\u00a0mg or 16\u2009mg once (QD) or twice (BID) daily, or 32\u2009mg QD,\u00a0BID or three times daily (TID) over a 12\u2010week period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 373 subjects were randomized to active treatment or placebo (~60% male, age\u2009~\u200956\u2009years, HbA1c 9%\u20109.8%; 75\u201084 mmol\/mol). Placebo\u2010adjusted HbA1c changes from baseline to Week 12 were observed with ORMD\u20100801 8\u00a0mg BID (\u22127.15\u2009\u00b1\u20093.57\u2009mmol\/mol [\u22120.65%\u2009\u00b1\u20090.33%];\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u20090.046). However, a significant site interaction was observed in two sites. After excluding these, HbA1c reduction was observed with 8\u00a0mg QD (\u22120.81\u2009\u00b1\u20090.37%; \u22128.89 \u00b1\u00a04.01\u00a0mmol\/mol;\u00a0\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u20090.028, n\u00a0=\u00a015), 8\u00a0mg BID (\u22120.82\u2009\u00b1\u20090.37%; \u22128.95 \u00b1\u00a04.08\u00a0mmol\/mol;\u00a0\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u20090.029, n\u00a0=\u00a017), 32\u2009mg QD (\u22120.54\u2009\u00b1\u20090.26%; \u22125.89 \u00b1\u00a02.78\u00a0mmol\/mol;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u20090.036, n\u00a0=\u00a069) and 32\u2009mg BID (\u22120.53\u2009\u00b1\u20090.26%; \u22125.80 \u00b1\u00a02.83\u00a0mmol\/mol;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u20090.042, n\u00a0=\u00a068). No effect was observed with 16\u2009mg QD (0.25\u2009\u00b1\u20090.37%; 2.76 \u00b1\u00a03.99\u00a0mmol\/mol;\u00a0\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u20090.48, n\u00a0=\u00a018), 16\u2009mg BID (\u22120.36\u2009\u00b1\u20090.40%; \u22123.97 \u00b1\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u20090.36, n\u00a0=\u00a015) or 32\u2009mg TID (\u22120.45\u2009\u00b1\u20090.27%, \u22124.89 \u00b1\u00a02.90\u00a0mmol\/mol;\u00a0\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u20090.093, n\u00a0=\u00a069). Continuous glucose monitor and serum glucose measurements showed similar trends but were not significant. ORMD\u20100801 was safe, well tolerated and not associated with weight gain or hypoglycaemia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Oral insulin (ORMD\u20100801) induced greater reductions in HbA1c when compared to placebo, and was safe and well tolerated in individuals with uncontrolled T2DM. The efficacy and safety findings support continued development of the 8\u2010mg dose at bedtime, which is currently being evaluated in two Phase 3 trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14901","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T02:09:10Z","timestamp":1666663750000},"page":"943-952","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Oral insulin (\n                    <scp>ORMD<\/scp>\n                    \u20100801) in type 2 diabetes mellitus: A\n                    <scp>dose\u2010finding 12\u2010week<\/scp>\n                    randomized\n                    <scp>placebo\u2010controlled<\/scp>\n                    study"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1151-1370","authenticated-orcid":false,"given":"Roy","family":"Eldor","sequence":"first","affiliation":[{"name":"Diabetes Unit, 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