{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:46:50Z","timestamp":1792118810957,"version":"4.4.0"},"reference-count":52,"publisher":"The Endocrine Society","issue":"5","funder":[{"name":"Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases"},{"DOI":"10.13039\/100000098","name":"National Institutes of Health Clinical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006545","name":"National Institute of Minority Health and Health Disparities","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006545","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Bench-to-Bedside and Back","award":["(381469)"],"award-info":[{"award-number":["(381469)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Elevated rates of gluconeogenesis are an early pathogenic feature of youth-onset type 2 diabetes (Y-T2D), but targeted first-line therapies are suboptimal, especially in African American (AA) youth. We evaluated glucose-lowering mechanisms of metformin and liraglutide by measuring rates of gluconeogenesis and \u03b2-cell function after therapy in AA Y-T2D.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this parallel randomized clinical trial, 22 youth with Y-T2D\u2014age 15.3 \u00b1 2.1 years (mean \u00b1 SD), 68% female, body mass index (BMI) 40.1 \u00b1 7.9\u2005kg\/m2, duration of diagnosis 1.8 \u00b1 1.3 years\u2014were randomized to metformin alone (Met) or metformin + liraglutide (Lira) (Met + Lira) and evaluated before and after 12 weeks. Stable isotope tracers were used to measure gluconeogenesis [2H2O] and glucose production [6,6-2H2]glucose after an overnight fast and during a continuous meal. \u03b2-cell function (sigma) and whole-body insulin sensitivity (mSI) were assessed during a frequently sampled 2-hour oral glucose tolerance test.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>At baseline, gluconeogenesis, glucose production, and fasting and 2-hour glucose were comparable in both groups, though Met + Lira had higher hemoglobin A1C. Met + Lira had a greater decrease from baseline in fasting glucose (\u22122.0 \u00b1 1.3 vs \u22120.6 \u00b1 0.9\u2005mmol\/L, P = .008) and a greater increase in sigma (0.72 \u00b1 0.68 vs \u22120.05 \u00b1 0.71, P = .03). The change in fractional gluconeogenesis was similar between groups (Met + Lira: \u22120.36 \u00b1 9.4 vs Met: 0.04 \u00b1 12.3%, P = .9), and there were no changes in prandial gluconeogenesis or mSI. Increased glucose clearance in both groups was related to sigma (r = 0.63, P = .003) but not gluconeogenesis or mSI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Among Y-T2D, metformin with or without liraglutide improved glycemia but did not suppress high rates of gluconeogenesis. Novel therapies that will enhance \u03b2-cell function and target the elevated rates of gluconeogenesis in Y-T2D are needed.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgad669","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T05:51:43Z","timestamp":1699941103000},"page":"1361-1370","source":"Crossref","is-referenced-by-count":15,"title":["Glycemia and Gluconeogenesis With Metformin and Liraglutide: A Randomized Trial in Youth-onset Type 2 Diabetes"],"prefix":"10.1210","volume":"109","author":[{"given":"Katrina B","family":"Dietsche","sequence":"first","affiliation":[{"name":"National Institute of Diabetes, Digestive and Kidney Diseases\/National Institutes of Health , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0949-4399","authenticated-orcid":false,"given":"Sheela N","family":"Magge","sequence":"additional","affiliation":[{"name":"Division of 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