Effects of Metformin, Metformin Plus Rosiglitazone, and Metformin Plus Lifestyle on Insulin Sensitivity and β-Cell Function in TODAY
Year: 2013
Type: article
Abstract: OBJECTIVE: The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) trial demonstrated that combination therapy with metformin plus rosiglitazone provided superior durability of glycemic control compared with metformin alone, with significantly lower treatment failure rates (38.6 vs. 51.7%), and metformin plus lifestyle was intermediate. Herein we describe the temporal changes in measures of β-cell function and insulin sensitivity over a 4-year period among the three treatments. RESEARCH DESIGN AND METHODS: TODAY participants (699) were tested periodically with an oral glucose tolerance test to determine insulin sensitivity (1/fasting insulin [1/IF]), insulinogenic index (ΔI(30)/ΔG(30)) or C-peptide index (ΔC(30)/ΔG(30)), and β-cell function relative to insulin sensitivity (oral disposition index [oDI]). RESULTS: During the first 6 months, metformin plus rosiglitazone exhibited a significantly greater improvement in insulin sensitivity and oDI versus metformin alone and versus metformin plus lifestyle; these improvements were sustained over 48 months of TODAY. Irrespective of treatment, those who failed to maintain glycemic control had significantly lower β-cell function (~50%), higher fasting glucose concentration, and higher HbA1c at randomization compared with those who did not fail. CONCLUSIONS: The beneficial change in insulin sensitivity and the resultant lower burden on β-cell function achieved in the first 6 months with metformin plus rosiglitazone appear to be responsible for its superior glycemic durability over metformin alone and metformin plus lifestyle. However, initial β-cell reserve and HbA1c at randomization are independent predictors of glycemic durability. Therefore, efforts to preserve β-cell function before significant loss occurs and to reduce HbA1c may be beneficial in the treatment of youth with type 2 diabetes.
Source: Diabetes Care
DOI: 10.2337/dc12-2393
Author: TODAY Study Group
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: General Clinical Research Center, Management of Pediatric Type 2 Diabetes Mellitus, Multi-Center Study of the Treatment of T2DM in Youth, Case Western Reserve University/Cleveland Clinic CTSA (UL1), Southern California Clinical and Translational Science Institute, Harvard Clinical and Translational Science Center (UL1), General Clinical Research Center, University of Pittsburgh Clinical and Translational Science Institute, Type 2 Diabetes in Youth: Beta Cell Preservation, Treatment Alternatives in Pediatric Type 2 Diabetes, TODAY2 Phase 2 (T2P2): Long-Term Post-Intervention Follow-Up, Institutional Clinical and Translational Science Award, University of Pittsburgh Clinical and Translational Science Institute, General Clinical Research Center, G606898507, General Clinical Research Center, General Clinical Research Center, Washington University Institute of Clinical and Translational Sciences, Washington University Institute of Clinical and Translational Sciences (UL1), Yale University Clinical and Translational Science Award Program, General Clinical Research Center, Clinical and Translational Science Collaborative of Cleveland, GENERAL CLINICAL RESEARCH CENTER, Colorado Clinical and Translational Science Institute (UL1)
OpenAlex ID: W59232989