Post-intervention Effects of Varying Treatment Arms on Glycemic Failure and Beta-Cell Function in the TODAY Study
Year: 2020
Type: other
Abstract: Objective: The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) trial demonstrated that glycemic failure rates were significantly lower in youth randomized to metformin plus rosiglitazone treatment compared to metformin alone or metformin plus intensive lifestyle intervention. At end of study, rosiglitazone was permanently discontinued, and routine diabetes care resumed. Herein, we report post-intervention glycemic failure rates in TODAY participants over an additional 36 months of follow-up for the three original treatment arms and describe insulin sensitivity and beta-cell function outcomes. Research Design and Methods: A total of 699 participants were randomized during TODAY, of whom 572 enrolled in the TODAY2 observational follow-up. Glycemic failure was defined as HbA1c ≥8% over a 6-month period or inability to wean from temporary insulin therapy within 3 months after acute metabolic decompensation during TODAY or a sustained HbA1c ≥8% over two consecutive visits during TODAY2. Oral glucose tolerance tests were conducted and insulin sensitivity, insulinogenic index, and oral disposition index (oDI) were calculated. Results: During the 36 months of TODAY2, glycemic failure rates did not differ among participants by original treatment group assignment. Insulin sensitivity and beta-cell function deteriorated rapidly during the 36 months of TODAY2 routine diabetes care, but did not differ by treatment group assignment. Conclusions: The added benefit of preventing glycemic failure by using rosiglitazone as a second agent in youth-onset type 2 diabetes did not persist after its discontinuation. More work is needed to address this rapid progression to avoid long-term diabetes complications.
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Funders: Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, GlaxoSmithKline, Sanofi, LifeScan, Massachusetts General Hospital, Yale University, Children's Hospital of Philadelphia, Children's Hospital Los Angeles, Washington University in St. Louis, University of Oklahoma, Case Western Reserve University, BD, National Institutes of Health, University of Oklahoma Health Sciences Center, University of Colorado Denver, NIH Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, NIH Clinical Center, Children's Hospital of Pittsburgh
Awards: G1114177658, G1134233510, G130883262, G1415392549, G1415791185, G145157345, G1452406238, Management of Pediatric Type 2 Diabetes Mellitus, G149689038, G158963794, G1846855846, G1885171633, G1922015097, G20328578, G2236591371, G2250838539, G2290786691, Case Western Reserve University/Cleveland Clinic CTSA (UL1), G2328791590, G2427822680, G2445381393, G246532802, G2527449299, G2540315505, G27536180, G278975345, G284260254, G3029844320, G3089208431, G3247330982, G3285764141, G3394423889, Harvard Clinical and Translational Science Center (UL1), G3499161329, University of Pittsburgh Clinical and Translational Science Institute, G3770033996, G3770193043, G3832661877, G3976977953, Type 2 Diabetes in Youth: Beta Cell Preservation, G413336477, G4412971278, G4455723224, G4467312596, G4748915099, G475936976, G4884696667, G4948594166, G5021569069, G523627176, G5248153975, G547031277, G5495349041, G5587521943, G5640239032, G5973391453, G606898507, General Clinical Research Center, G6246743082, G653690408, G6716629419, G733747580, G7432973588, G7503690254, G7635370081, G7804600378, G800374514, Yale University Clinical and Translational Science Award Program, G8377578562, G862824631, G881343144, G889535532, G8900235588, G9000000078, G9000016200, G9000020237, G9000032576, G9000037440, G9000042762, G9000052321, G9000060836, G9000068737, G9000071235, G9000083019, G9000085504, G9000109397, G9000199034, G9000238543, G9000259551, G9000271159, G9000281696, G9000349463
OpenAlex ID: W4252611575