{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:43:36Z","timestamp":1789983816612,"version":"4.0.1"},"reference-count":20,"publisher":"American Diabetes Association","issue":"1","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"\n OBJECTIVE<\/jats:title>\n Hypoglycemia is a leading risk of glucose-lowering therapy. Treatment with insulin glargine compared with standard care early in the course of dysglycemia in the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial provides information on the frequency and predictors of hypoglycemia in this setting.<\/jats:p>\n <\/jats:sec>\n \n RESEARCH DESIGN AND METHODS<\/jats:title>\n A total of 12,537 people with high cardiovascular risk and dysglycemia treated with one or no oral glucose-lowering agents were randomized to add glargine titrated to a fasting glucose level of \u22645.3 mmol\/L (\u226495 mg\/dL) or to use standard therapies. Independent associations of both nonsevere hypoglycemia (symptomatic and confirmed with a glucose level of \u22643 mmol\/L [\u226454 mg\/dL]) and severe hypoglycemia with characteristics at baseline, treatment allocation, and average HbA1c were assessed by Cox proportional hazards models.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n During a median follow-up period of 6.2 years, 28% of participants reported nonsevere hypoglycemia, and 3.8% reported severe hypoglycemia. Prior use of a sulfonylurea and allocation to glargine independently predicted a higher risk for both categories of participants. Nonsevere events were independently associated with younger age, lower BMI, the presence of diabetes, and higher baseline HbA1c level. Severe events were associated with older age, hypertension, higher serum creatinine level, and lower cognitive function, but not baseline glycemic status. Progressively higher on-treatment HbA1c level was associated with a lower risk of nonsevere events in both treatment groups; a lower risk of severe events in the glargine group, and a higher risk of severe events with standard care.<\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n Hypoglycemia was relatively uncommon in the ORIGIN trial, but was more frequent with sulfonylurea use at baseline and allocation to glargine. Nonsevere and severe events were associated with different clinical characteristics, awareness of which may guide individualized therapy.<\/jats:p>\n <\/jats:sec>","DOI":"10.2337\/dc14-1329","type":"journal-article","created":{"date-parts":[[2014,10,29]],"date-time":"2014-10-29T06:19:04Z","timestamp":1414563544000},"page":"22-28","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":66,"title":["Predictors of Nonsevere and Severe Hypoglycemia During Glucose-Lowering Treatment With Insulin Glargine or Standard Drugs in the ORIGIN Trial"],"prefix":"10.2337","volume":"38","author":[{"name":"The ORIGIN Trial Investigators","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2014,10,28]]},"reference":[{"key":"2022031301404018800_B1","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1056\/NEJMoa1003795","article-title":"Severe hypoglycemia and risks of vascular events and death","volume":"363","author":"Zoungas","year":"2010","journal-title":"N Engl J Med"},{"key":"2022031301404018800_B2","doi-asserted-by":"crossref","first-page":"S132","DOI":"10.2337\/dc11-s220","article-title":"Hypoglycemia and cardiovascular risks","volume":"34","author":"Frier","year":"2011","journal-title":"Diabetes Care"},{"key":"2022031301404018800_B3","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1161\/CIRCULATIONAHA.110.948489","article-title":"Serious cardiovascular outcomes in diabetes: the role of hypoglycemia","volume":"123","author":"Yakubovich","year":"2011","journal-title":"Circulation"},{"key":"2022031301404018800_B4","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1136\/hrt.2008.152835","article-title":"for the DIGAMI 2 investigators. 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