{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:07:39Z","timestamp":1783548459493,"version":"3.55.0"},"reference-count":22,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"unspecified","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Xeris Pharmaceuticals, Inc.","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Diab Res Care"],"accepted":{"date-parts":[[2021,8,25]]},"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>To prevent medical sequelae of severe hypoglycemic emergencies, prompt and reliable rescue intervention is critically important. A ready-to-use, liquid stable glucagon, administered subcutaneously by glucagon autoinjector (GAI), Gvoke HypoPen (glucagon injection; Xeris Pharmaceuticals), was evaluated for rescue treatment of severe hypoglycemia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Research design and methods<\/jats:title>\n                  <jats:p>Two phase III, randomized, controlled, blinded, non-inferiority crossover studies were conducted in 161 adults with type 1 diabetes to compare 1\u2009mg doses of GAI versus glucagon emergency kit (GEK) for treating insulin-induced severe hypoglycemia. Efficacy was evaluated as either a return of plasma glucose to &gt;70\u2009mg\/dL (3.9\u2009mmol\/L) or increase \u226520\u2009mg\/dL (1.1\u2009mmol\/L) from a baseline glucose of &lt;50\u2009mg\/dL (2.9\u2009mmol\/L), within 30\u2009min of dosing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>For successful plasma glucose recovery within 30\u2009min, treatment with GAI was non-inferior to GEK. Treatment with GAI was non-inferior to GEK for a plasma glucose &gt;70\u2009mg\/dL (3.9\u2009mmol\/L) or neuroglycopenic symptom relief within 30\u2009min. From administration of glucagon, the mean time to achieve plasma glucose &gt;70\u2009mg\/dL (3.9\u2009mmol\/L) or increase \u226520\u2009mg\/dL (1.1\u2009mmol\/L) was 13.8\u00b15.6\u2009min for GAI and 10.0\u00b13.6\u2009min for GEK. This mean time does not account for the significantly shorter (p&lt;0.0001) drug preparation and administration time for GAI (27.3\u00b119.7\u2009s) versus GEK (97.2\u00b145.1\u2009s). The incidence of treatment emergent adverse events was comparable in both groups.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A ready-to-use GAI was non-inferior to GEK, with a similar tolerability profile. GAI is an effective, safe, and well-tolerated rescue treatment for severe hypoglycemia and is a viable alternative to GEK.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration numbers<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02656069\">NCT02656069<\/jats:ext-link> and <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03439072\">NCT03439072<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjdrc-2021-002137","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T00:07:43Z","timestamp":1633824463000},"page":"e002137","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Comparison of a ready-to-use liquid glucagon injection administered by autoinjector to glucagon emergency kit for the symptomatic relief of severe hypoglycemia: two randomized crossover non-inferiority studies"],"prefix":"10.1136","volume":"9","clinical-trial-number":[{"clinical-trial-number":"nct02656069","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03439072","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Mark P","family":"Christiansen","sequence":"first","affiliation":[{"name":"Diablo Clinical Research, Walnut Creek, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Cummins","sequence":"additional","affiliation":[{"name":"Clinical Development, Xeris Pharmaceuticals Inc, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Prestrelski","sequence":"additional","affiliation":[{"name":"Clinical Development, Xeris Pharmaceuticals Inc, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole C","family":"Close","sequence":"additional","affiliation":[{"name":"EmpiriStat Inc, Kitty Hawk, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Clinical Development, Xeris Pharmaceuticals Inc, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0581-5412","authenticated-orcid":false,"given":"Khaled","family":"Junaidi","sequence":"additional","affiliation":[{"name":"Clinical Development, Xeris Pharmaceuticals Inc, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"key":"2025073113051053000_9.1.e002137.1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.4.1176"},{"key":"2025073113051053000_9.1.e002137.2","doi-asserted-by":"publisher","DOI":"10.2337\/dc21-S006"},{"key":"2025073113051053000_9.1.e002137.3","doi-asserted-by":"crossref","first-page":"337","DOI":"10.2147\/DMSO.S20633","article-title":"Treatment of severe diabetic hypoglycemia with glucagon: an underutilized therapeutic approach","volume":"4","author":"Kedia","year":"2011","journal-title":"Diabetes Metab Syndr Obes"},{"key":"2025073113051053000_9.1.e002137.4","doi-asserted-by":"publisher","DOI":"10.1177\/1932296814549597"},{"key":"2025073113051053000_9.1.e002137.5","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1089\/dia.2016.0460","article-title":"Faster use and fewer failures with needle-free nasal glucagon versus injectable glucagon in severe hypoglycemia rescue: a simulation study","volume":"19","author":"Yale","year":"2017","journal-title":"Diabetes Technol Ther"},{"key":"2025073113051053000_9.1.e002137.6","unstructured":"Ching K , Andre A , Crick M , et al . Biodel's glucagon emergency management auto reconstitution device demonstrates superior usability compared to market glucagon kits in human factors study. 15th Annual Meeting of the Diabetes Technology Society; October 22-24, Bethesda, MD, 2015:A15."},{"key":"2025073113051053000_9.1.e002137.7","doi-asserted-by":"crossref","first-page":"407","DOI":"10.4158\/EP-2019-0502","article-title":"Nasal glucagon delivery is more successful than injectable delivery: a simulated severe hypoglycemia rescue","volume":"26","author":"Settles","year":"2020","journal-title":"Endocr Pract"},{"key":"2025073113051053000_9.1.e002137.8","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1089\/dia.2019.0148","article-title":"Human factors usability and validation studies of a glucagon autoinjector in a simulated severe hypoglycemia rescue situation","volume":"21","author":"Valentine","year":"2019","journal-title":"Diabetes Technol Ther"},{"key":"2025073113051053000_9.1.e002137.9","doi-asserted-by":"crossref","first-page":"123","DOI":"10.4158\/EP15831.OR","article-title":"Glucagon prescription patterns in patients with either type 1 or 2 diabetes with newly prescribed insulin","volume":"22","author":"Mitchell","year":"2016","journal-title":"Endocr Pract"},{"key":"2025073113051053000_9.1.e002137.10","doi-asserted-by":"publisher","DOI":"10.1177\/1932296814565131"},{"key":"2025073113051053000_9.1.e002137.11","unstructured":"Gvoke\u00ae . Gvoke\u00ae package insert, 2019. Available: https:\/\/www.gvokeglucagon.com\/pdf\/gvoke-prescribing-information.pdf"},{"key":"2025073113051053000_9.1.e002137.12","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1080\/17425247.2019.1653278","article-title":"Human factors studies of a prefilled syringe with stable liquid glucagon in a simulated severe hypoglycemia rescue situation","volume":"16","author":"Newswanger","year":"2019","journal-title":"Expert Opin Drug Deliv"},{"key":"2025073113051053000_9.1.e002137.13","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0022-3565(25)08751-8","article-title":"Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes","volume":"82","author":"Draize","year":"1944","journal-title":"J Pharmacol Exp Ther"},{"key":"2025073113051053000_9.1.e002137.14","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.17.7.697"},{"key":"2025073113051053000_9.1.e002137.15","unstructured":"R Core Team . R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing, 2020. https:\/\/www.R-project.org\/"},{"key":"2025073113051053000_9.1.e002137.16","doi-asserted-by":"publisher","DOI":"10.1177\/1932296816653141"},{"key":"2025073113051053000_9.1.e002137.17","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1210\/jc.2017-00591","article-title":"Efficacy and safety of mini-dose glucagon for treatment of nonsevere hypoglycemia in adults with type 1 diabetes","volume":"102","author":"Haymond","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"2025073113051053000_9.1.e002137.18","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-2124"},{"key":"2025073113051053000_9.1.e002137.19","doi-asserted-by":"publisher","DOI":"10.2337\/diaclin.24.3.115"},{"key":"2025073113051053000_9.1.e002137.20","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-1402"},{"key":"2025073113051053000_9.1.e002137.21","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1498"},{"key":"2025073113051053000_9.1.e002137.22","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1606"}],"container-title":["BMJ Open Diabetes Research &amp; Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjdrc-2021-002137","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T20:05:17Z","timestamp":1753992317000},"score":1,"resource":{"primary":{"URL":"https:\/\/drc.bmj.com\/lookup\/doi\/10.1136\/bmjdrc-2021-002137"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":22,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,10,7]]},"published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1136\/bmjdrc-2021-002137"],"URL":"https:\/\/doi.org\/10.1136\/bmjdrc-2021-002137","relation":{},"ISSN":["2052-4897"],"issn-type":[{"value":"2052-4897","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10]]}}}