{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T08:20:22Z","timestamp":1790410822437,"version":"4.1.0"},"reference-count":15,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,4,12]],"date-time":"2020-04-12T00:00:00Z","timestamp":1586649600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To compare nasal glucagon (NG) with intramuscular glucagon (IMG) for the treatment of insulin\u2010induced hypoglycaemia in Japanese patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>This phase 3, randomized, open\u2010label, two\u2010treatment, two\u2010period crossover non\u2010inferiority study enrolled Japanese adults with T1DM or T2DM on insulin therapy, with glycated haemoglobin levels \u226486 mmol\/mol (\u226410%). After \u22658 hours of fasting, hypoglycaemia was induced with human regular insulin (intravenous infusion). Patients received NG 3 mg or IMG 1 mg approximately 5 minutes after insulin termination. The primary endpoint was the proportion of patients achieving treatment success [plasma glucose (PG) increase to \u22653.9 mmol\/L (\u226570 mg\/dL) or \u22651.1 mmol\/L (\u226520 mg\/dL) increase from the PG nadir within 30\u2009minutes of receiving glucagon]. Non\u2010inferiority was declared if the upper limit of the two\u2010sided 95% confidence interval (CI) of the mean difference in the percentage of patients achieving treatment success (IMG minus NG) was &lt;10%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seventy\u2010five patients with T1DM (n = 34) or T2DM (n = 41) were enrolled; 72 patients (50 men, 22 women) received \u22651 study drug dose (T1DM, n = 33; T2DM, n = 39). Sixty\u2010eight patients completed the study and were evaluable. All NG\u2010 and IMG\u2010treated patients achieved treatment success (treatment arm difference: 0%; upper limit of two\u2010sided 95% CI 1.47%); NG met prespecified conditions defining non\u2010inferiority versus IMG. Glucagon was rapidly absorbed after both nasal and intramuscular administration; PG profiles were similar between administration routes during the first 60\u2009minutes post dose. Study drug\u2010related treatment\u2010emergent adverse events affecting &gt;2 patients were rhinalgia, increased blood pressure, nausea, ear pain and vomiting in the NG group, and nausea and vomiting in the IMG group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Nasal glucagon was non\u2010inferior to IMG for successful treatment of insulin\u2010induced hypoglycaemia in Japanese patients with T1DM\/T2DM, supporting use of NG as a rescue treatment for severe hypoglycaemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14019","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T02:08:43Z","timestamp":1583114923000},"page":"1167-1175","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Nasal glucagon as a viable alternative for treating insulin\u2010induced hypoglycaemia in Japanese patients with type 1 or type 2 diabetes: A phase 3 randomized crossover study"],"prefix":"10.1111","volume":"22","author":[{"given":"Munehide","family":"Matsuhisa","sequence":"first","affiliation":[{"name":"Diabetes Therapeutics and Research Centre Institute of Advanced Medical Sciences, Tokushima University  Tokushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Takita","sequence":"additional","affiliation":[{"name":"Medicine Development Unit\u2010Japan and Medical Affairs, Eli Lilly Japan K.K.  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risa","family":"Nasu","sequence":"additional","affiliation":[{"name":"Medicine Development Unit\u2010Japan and Medical Affairs, Eli Lilly Japan K.K.  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Nagai","sequence":"additional","affiliation":[{"name":"Medicine Development Unit\u2010Japan and Medical Affairs, Eli Lilly Japan K.K.  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Ohwaki","sequence":"additional","affiliation":[{"name":"Medicine Development Unit\u2010Japan and Medical Affairs, Eli Lilly Japan K.K.  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Shinjuku Research Park Clinic  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1932296814557518"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-007-0599-y"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-4127"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.12491"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.4103\/2230-8210.117219"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S20633"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01454.x"},{"key":"e_1_2_9_9_1","unstructured":"SuicoJ H\u00f6velmannU ZhangS et al. Nasal glucagon: a viable alternative to treat insulin\u2010induced hypoglycaemia in adults with type 1 diabetes. 54th Annual Meeting of the European Association for the Study of Diabetes. Berlin Germany; October 1\u20135 2018.https:\/\/www.easd.org\/virtualmeeting\/home.html#!resources\/nasal\u2010glucagon\u2010a\u2010viable\u2010alternative\u2010to\u2010treat\u2010insulin\u2010induced\u2010hypoglycaemia\u2010in\u2010adults\u2010with\u2010type\u20101\u2010diabetes\u201056ea02bc\u20107c76\u201040fe\u2010a2c8\u20102ebd92aa0e0f. Accessed December 13 2019."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13278"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/pedi.12668"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2016.0460"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1498"},{"key":"e_1_2_9_14_1","unstructured":"World Health Organization. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia.https:\/\/www.who.int\/diabetes\/publications\/Definition%20and%20diagnosis%20of%20diabetes_new.pdfAccessed June 12 2019."},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12790"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1606"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdom.14019","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.14019","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.14019","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.14019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T23:56:02Z","timestamp":1761868562000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.14019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,12]]},"references-count":15,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1111\/dom.14019"],"URL":"https:\/\/doi.org\/10.1111\/dom.14019","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/DOM.14019\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14019\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14019\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14019\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14019\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14019\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14019\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14019\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14019\/v1\/decision1","asserted-by":"object"}]},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,12]]},"assertion":[{"value":"2019-11-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}