{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:52:09Z","timestamp":1790833929015,"version":"4.1.0"},"reference-count":36,"publisher":"American Diabetes Association","issue":"12","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,12,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Clinical studies evaluating the effects of medications on \u03b2-cell function in type 2 diabetes (T2DM) are compromised by an inability to determine the actual baseline degree of \u03b2-cell dysfunction independent of the reversible dysfunction induced by hyperglycemia (glucotoxicity). Short-term intensive insulin therapy (IIT) is a strategy for eliminating glucotoxicity before randomization. This study determined whether liraglutide can preserve \u03b2-cell function over 48 weeks in early T2DM following initial elimination of glucotoxicity with IIT.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>In this double-blind, randomized, placebo-controlled trial, 51 patients with T2DM of 2.6 \u00b1 1.9 years' duration and an A1C of 6.8 \u00b1 0.8% (51 \u00b1 8.7 mmol\/mol) completed 4 weeks of IIT before randomization to daily subcutaneous liraglutide or placebo injection, with serial assessment of \u03b2-cell function by Insulin Secretion-Sensitivity Index-2 (ISSI-2) on oral glucose tolerance test performed every 12 weeks.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>The primary outcome of baseline-adjusted ISSI-2 at 48 weeks was higher in the liraglutide group than in the placebo group (339.8 \u00b1 27.8 vs. 229.3 \u00b1 28.4, P = 0.008). Baseline-adjusted HbA1c at 48 weeks was lower in the liraglutide group (6.2 \u00b1 0.1% vs. 6.6 \u00b1 0.1%, P = 0.055) (44 \u00b1 1.1 vs. 49 \u00b1 1.1 mmol\/mol). At each quarterly assessment, &amp;gt;50% of participants on liraglutide had an HbA1c \u22646.0% (42 mmol\/mol) and glucose tolerance in the nondiabetic range. Despite this level of glycemic control, no difference was found in the incidence of hypoglycemia between the liraglutide and placebo groups (P = 0.61). Two weeks after stopping treatment, however, the beneficial effect on ISSI-2 of liraglutide versus placebo was entirely lost (191.9 \u00b1 24.7 vs. 238.1 \u00b1 25.2, P = 0.20).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Liraglutide provides robust enhancement of \u03b2-cell function that is sustained over 48 weeks in early T2DM but lost upon cessation of therapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc14-0893","type":"journal-article","created":{"date-parts":[[2014,9,24]],"date-time":"2014-09-24T05:38:27Z","timestamp":1411537107000},"page":"3270-3278","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":124,"title":["Liraglutide and the Preservation of Pancreatic \u03b2-Cell Function in Early Type 2 Diabetes: The LIBRA Trial"],"prefix":"10.2337","volume":"37","clinical-trial-number":[{"clinical-trial-number":"nct01270789","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01270789","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Ravi","family":"Retnakaran","sequence":"first","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada"},{"name":"Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada"},{"name":"Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline K.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada"},{"name":"Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haysook","family":"Choi","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balakumar","family":"Swaminathan","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Zinman","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada"},{"name":"Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada"},{"name":"Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2014,11,8]]},"reference":[{"key":"2022031219374120400_B1","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1001\/jama.281.21.2005","article-title":"Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49)","volume":"281","author":"Turner","year":"1999","journal-title":"JAMA"},{"key":"2022031219374120400_B2","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1007\/s00125-009-1321-z","article-title":"The beta cell lesion in type 2 diabetes: there has to be a primary functional abnormality","volume":"52","author":"Kahn","year":"2009","journal-title":"Diabetologia"},{"key":"2022031219374120400_B3","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1210\/10.1210\/er.2006-0038","article-title":"Beta-cell failure in diabetes and preservation by clinical treatment","volume":"28","author":"Wajchenberg","year":"2007","journal-title":"Endocr Rev"},{"key":"2022031219374120400_B4","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1056\/NEJMoa066224","article-title":"Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy","volume":"355","author":"Kahn","year":"2006","journal-title":"N Engl J Med"},{"key":"2022031219374120400_B5","doi-asserted-by":"crossref","first-page":"4206","DOI":"10.1210\/jc.2010-0668","article-title":"Targeting beta-cell function early in the course of therapy for type 2 diabetes mellitus","volume":"95","author":"Leahy","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031219374120400_B6","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1210\/jc.2011-0246","article-title":"Preservation of \u03b2-cell function: the key to diabetes prevention","volume":"96","author":"DeFronzo","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031219374120400_B7","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1210\/jcem-42-2-222","article-title":"Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance tests","volume":"42","author":"Brunzell","year":"1976","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031219374120400_B8","doi-asserted-by":"crossref","first-page":"E1398","DOI":"10.1152\/ajpendo.00447.2013","article-title":"Determinants of reversibility of \u03b2-cell dysfunction in response to short-term intensive insulin therapy in patients with early type 2 diabetes","volume":"305","author":"Kramer","year":"2013","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2022031219374120400_B9","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1463-1326.2012.01658.x","article-title":"Short-term intensified insulin treatment in type 2 diabetes: long-term effects on \u03b2-cell function","volume":"14","author":"Retnakaran","year":"2012","journal-title":"Diabetes Obes Metab"},{"key":"2022031219374120400_B10","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1111\/j.1463-1326.2010.01254.x","article-title":"Initial short-term intensive insulin therapy as a strategy for evaluating the preservation of beta-cell function with oral antidiabetic medications: a pilot study with sitagliptin","volume":"12","author":"Retnakaran","year":"2010","journal-title":"Diabetes Obes Metab"},{"key":"2022031219374120400_B11","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.2337\/dc11-2170","article-title":"\u03b2-cell function preservation after 3.5 years of intensive diabetes therapy","volume":"35","author":"Harrison","year":"2012","journal-title":"Diabetes Care"},{"key":"2022031219374120400_B12","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1172\/JCI30076","article-title":"The role of gut hormones in glucose homeostasis","volume":"117","author":"Drucker","year":"2007","journal-title":"J Clin Invest"},{"key":"2022031219374120400_B13","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.cmet.2013.04.008","article-title":"Pharmacology, physiology, and mechanisms of incretin hormone action","volume":"17","author":"Campbell","year":"2013","journal-title":"Cell Metab"},{"key":"2022031219374120400_B14","doi-asserted-by":"crossref","first-page":"4397","DOI":"10.1210\/en.2002-220405","article-title":"Glucagon-like peptide-1 promotes islet cell growth and inhibits apoptosis in Zucker diabetic rats","volume":"143","author":"Farilla","year":"2002","journal-title":"Endocrinology"},{"key":"2022031219374120400_B15","doi-asserted-by":"crossref","first-page":"124","DOI":"10.2337\/diabetes.52.1.124","article-title":"Glucagon-like peptide 1 induces pancreatic beta-cell proliferation via transactivation of the epidermal growth factor receptor","volume":"52","author":"Buteau","year":"2003","journal-title":"Diabetes"},{"key":"2022031219374120400_B16","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.2337\/dc11-0986","article-title":"Incretin-based therapy and the quest for sustained improvements in \u03b2-cell health","volume":"34","author":"Drucker","year":"2011","journal-title":"Diabetes Care"},{"key":"2022031219374120400_B17","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.2337\/dc13-2591","article-title":"Glycemic variability in patients with early type 2 diabetes: the impact of improvement in \u03b2-cell function","volume":"37","author":"Kramer","year":"2014","journal-title":"Diabetes Care"},{"key":"2022031219374120400_B18","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1463-1326.2009.01129.x","article-title":"The response to short-term intensive insulin therapy in type 2 diabetes","volume":"12","author":"Retnakaran","year":"2010","journal-title":"Diabetes Obes Metab"},{"key":"2022031219374120400_B19","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1016\/j.jcjd.2013.01.011","article-title":"Definition, classification and diagnosis of diabetes, prediabetes and metabolic syndrome","volume":"37","author":"Canadian Diabetes Association Clinical Practice Guidelines Expert Committee","year":"2013","journal-title":"Can J Diabetes"},{"key":"2022031219374120400_B20","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.2337\/diacare.22.9.1462","article-title":"Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp","volume":"22","author":"Matsuda","year":"1999","journal-title":"Diabetes Care"},{"key":"2022031219374120400_B21","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"2022031219374120400_B22","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1038\/oby.2008.307","article-title":"Hyperbolic relationship between insulin secretion and sensitivity on oral glucose tolerance test","volume":"16","author":"Retnakaran","year":"2008","journal-title":"Obesity (Silver Spring)"},{"key":"2022031219374120400_B23","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1111\/j.1464-5491.2009.02841.x","article-title":"Evaluation of proposed oral disposition index measures in relation to the actual disposition index","volume":"26","author":"Retnakaran","year":"2009","journal-title":"Diabet Med"},{"key":"2022031219374120400_B24","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0140-6736(10)60746-5","article-title":"Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study","volume":"376","author":"Zinman","year":"2010","journal-title":"Lancet"},{"key":"2022031219374120400_B25","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.2337\/db11-0465","article-title":"Prospective associations of vitamin D with \u03b2-cell function and glycemia: the PROspective Metabolism and ISlet cell Evaluation (PROMISE) cohort study","volume":"60","author":"Kayaniyil","year":"2011","journal-title":"Diabetes"},{"key":"2022031219374120400_B26","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.2337\/dc10-0351","article-title":"Beta-cell function declines within the first year postpartum in women with recent glucose intolerance in pregnancy","volume":"33","author":"Retnakaran","year":"2010","journal-title":"Diabetes Care"},{"key":"2022031219374120400_B27","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.2337\/dc11-0046","article-title":"Changes over time in glycemic control, insulin sensitivity, and beta-cell function in response to low-dose metformin and thiazolidinedione combination therapy in patients with impaired glucose tolerance","volume":"34","author":"Retnakaran","year":"2011","journal-title":"Diabetes Care"},{"key":"2022031219374120400_B28","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.2337\/db08-1607","article-title":"Changes in insulin sensitivity and insulin release in relation to glycemia and glucose tolerance in 6,414 Finnish men","volume":"58","author":"Stanc\u00e1kov\u00e1","year":"2009","journal-title":"Diabetes"},{"key":"2022031219374120400_B29","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1056\/NEJMoa1010949","article-title":"Pioglitazone for diabetes prevention in impaired glucose tolerance","volume":"364","author":"DeFronzo","year":"2011","journal-title":"N Engl J Med"},{"key":"2022031219374120400_B30","doi-asserted-by":"crossref","first-page":"3920","DOI":"10.2337\/db13-0265","article-title":"Prevention of diabetes with pioglitazone in ACT NOW: physiologic correlates","volume":"62","author":"Defronzo","year":"2013","journal-title":"Diabetes"},{"key":"2022031219374120400_B31","doi-asserted-by":"crossref","first-page":"3607","DOI":"10.2337\/dc13-0520","article-title":"Prediction of diabetes based on baseline metabolic characteristics in individuals at high risk","volume":"36","author":"Defronzo","year":"2013","journal-title":"Diabetes Care"},{"key":"2022031219374120400_B32","doi-asserted-by":"crossref","first-page":"780","DOI":"10.2337\/dc13-1879","article-title":"Restoring Insulin Secretion (RISE): design of studies of \u03b2-cell preservation in prediabetes and early type 2 diabetes across the life span","volume":"37","author":"RISE Consortium","year":"2014","journal-title":"Diabetes Care"},{"key":"2022031219374120400_B33","doi-asserted-by":"crossref","first-page":"762","DOI":"10.2337\/dc08-1797","article-title":"One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial","volume":"32","author":"Bunck","year":"2009","journal-title":"Diabetes Care"},{"key":"2022031219374120400_B34","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.2337\/dc11-0291","article-title":"Effects of exenatide on measures of \u03b2-cell function after 3 years in metformin-treated patients with type 2 diabetes","volume":"34","author":"Bunck","year":"2011","journal-title":"Diabetes Care"},{"key":"2022031219374120400_B35","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1016\/S0140-6736(08)60762-X","article-title":"Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial","volume":"371","author":"Weng","year":"2008","journal-title":"Lancet"},{"key":"2022031219374120400_B36","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S2213-8587(13)70006-8","article-title":"Short-term intensive insulin therapy in type 2 diabetes: a systematic review and meta-analysis","volume":"1","author":"Kramer","year":"2013","journal-title":"Lancet Diabetes Endocrinol"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/37\/12\/3270\/619861\/3270.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/37\/12\/3270\/619861\/3270.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T21:17:49Z","timestamp":1647119869000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/37\/12\/3270\/29432\/Liraglutide-and-the-Preservation-of-Pancreatic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,8]]},"references-count":36,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2014,11,8]]},"published-print":{"date-parts":[[2014,12,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc14-0893","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,8]]}}}