Metformin monotherapy in youth with recent onset type 2 diabetes: experience from the prerandomization run-in phase of the TODAY study
Lori Laffel, Nancy Chang, Margaret Grey, Dan Hale, Laurie Higgins, Kathryn Hirst, Roberto Izquierdo, Mary Larkin, Christina Macha, Trang Pham, Aimee Wauters, Ruth S Weinstock, TODAY Study Group, S McKay, B Anderson, C Bush, S Gunn, M Haymond, H Holden, K Hwu, S Jones, McGirk, B Schreiner, S Thamotharan, M Zarate, L Cuttler, E Abrams, T Casey, W Dahms, A Davis, A Haider, S Huestis, C Ievers-Landis, B Kaminski, M Koontz, S MacLeish, P McGuigan, S Narasimhan, D Rogers, M Geffner, V Barraza, N Chang, B Conrad, D Dreimane, S Estrada, L Fisher, E Fleury-Milfort, S Hernandez, B Hollen, F Kaufman, E Law, V Mansilla, D Miller, C Muñnoz, R Ortiz, J Sanchez, A Ward, K Wexler, Y Xu, P Yasuda, L Levitt Katz, R Berkowitz, K Gralewski, B Johnson, J Kaplan, C Keating, C Lassiter, T Lipman, G McGinley, H McKnight, B Schwartzman, S Willi, S Arslanian, F Bacha, S Foster, B Galvin, T Hannon, A Kriska, I Libman, M Marcus, K Porter, T Songer, R Venditti, R Goland, R Cain, I Fennoy, D Gallagher, P Kringas, N Leibel, R Motaghedi, D Ng, M Ovalles, M Pellizzari, R Rapaport, K Robbins, D Seidman, L Siegel-Czarkowski, P Speiser, L Laffel, A Goebel-Fabbri, M Hall, M Higgins, M Malloy, K Milaszewski, L Orkin, A Rodriguez-Ventura, D Nathan, L Bissett, K Blumenthal, L Delahanty, V Goldman, A Goseco, M Larkin, L Levitsky, R McEachern, K Milaszewski, D Norman, B Nwosu, S Park-Bennett, D Richards, N Sherry, B Steiner, S Tollefsen, S Carnes, D Dempsher, D Flomo, V Kociela, T Whelan, B Wolff, R Weinstock, D Bowerman, S Bristol, J Bulger, J Hartsig, R Izquierdo, J Kearns, R Saletsky, P Trief, P Zeitler, N Abramson, A Bradhurst, N Celona-Jacobs, J Higgins, A Hull, M Kelsey, G Klingensmith, K Nadeau, T Witten, K Copeland, E Boss, R Brown, J Chadwick, L Chalmers, S Chernausek, C Macha, R Newgent, A Nordyke, D Olson, T Poulsen, L Pratt, J Preske, J Schanuel, J Smith, S Sternlof, J Lynch, N Amodei, R Barajas, R Swisher, C Cody, D Hale, J Hernandez, C Ibarra, E Morales, S Rivera, G Rupert, A Wauters, N White, A Arbeláez, J Jones, T Jones, M Sadler, M Tanner, A Timpson, R Welch, S Caprio, M Grey, C Guandalini, S Lavietes, M Mignosa, P Rose, A Syme, W Tamborlane, S Edelstein, P Feit, N Grover, C Long, L Pyle, B Linder, S Marcovina, J Chmielewski, M Ramirez, G Strylewicz, J Shepherd, B Fan, L Marquez, M Sherman, J Wang, E Mayer-Davis, Y Liu, M Nichols, D Wilfley, D Aldrich-Rasche, K Franklin, D Laughlin, G Leibach, C Massmann, M Mills, D O'Brien, J Patterson, T Tibbs, D Van Buren, A Vannuci, P Zhang, M Palmert, L Epstein, J Silverstein, Lori Laffel, Nancy Chang, Margaret Grey, Dan Hale, Laurie Higgins, Kathryn Hirst, Roberto Izquierdo, Mary Larkin, Christina Macha, Trang Pham, Aimee Wauters, Ruth S Weinstock, TODAY Study Group, S McKay, B Anderson, C Bush, S Gunn, M Haymond, H Holden, K Hwu, S Jones, McGirk, B Schreiner, S Thamotharan, M Zarate, L Cuttler, E Abrams, T Casey, W Dahms, A Davis, A Haider, S Huestis, C Ievers-Landis, B Kaminski, M Koontz, S MacLeish, P McGuigan, S Narasimhan, D Rogers, M Geffner, V Barraza, N Chang, B Conrad, D Dreimane, S Estrada, L Fisher, E Fleury-Milfort, S Hernandez, B Hollen, F Kaufman, E Law, V Mansilla, D Miller, C Muñnoz, R Ortiz, J Sanchez, A Ward, K Wexler, Y Xu, P Yasuda, L Levitt Katz, R Berkowitz, K Gralewski, B Johnson, J Kaplan, C Keating, C Lassiter, T Lipman, G McGinley, H McKnight, B Schwartzman, S Willi, S Arslanian, F Bacha, S Foster, B Galvin, T Hannon, A Kriska, I Libman, M Marcus, K Porter, T Songer, R Venditti, R Goland, R Cain, I Fennoy, D Gallagher, P Kringas, N Leibel, R Motaghedi, D Ng, M Ovalles, M Pellizzari, R Rapaport, K Robbins, D Seidman, L Siegel-Czarkowski, P Speiser, L Laffel, A Goebel-Fabbri, M Hall, M Higgins, M Malloy, K Milaszewski, L Orkin, A Rodriguez-Ventura, D Nathan, L Bissett, K Blumenthal, L Delahanty, V Goldman, A Goseco, M Larkin, L Levitsky, R McEachern, K Milaszewski, D Norman, B Nwosu, S Park-Bennett, D Richards, N Sherry, B Steiner, S Tollefsen, S Carnes, D Dempsher, D Flomo, V Kociela, T Whelan, B Wolff, R Weinstock, D Bowerman, S Bristol, J Bulger, J Hartsig, R Izquierdo, J Kearns, R Saletsky, P Trief, P Zeitler, N Abramson, A Bradhurst, N Celona-Jacobs, J Higgins, A Hull, M Kelsey, G Klingensmith, K Nadeau, T Witten, K Copeland, E Boss, R Brown, J Chadwick, L Chalmers, S Chernausek, C Macha, R Newgent, A Nordyke, D Olson, T Poulsen, L Pratt, J Preske, J Schanuel, J Smith, S Sternlof, J Lynch, N Amodei, R Barajas, R Swisher, C Cody, D Hale, J Hernandez, C Ibarra, E Morales, S Rivera, G Rupert, A Wauters, N White, A Arbeláez, J Jones, T Jones, M Sadler, M Tanner, A Timpson, R Welch, S Caprio, M Grey, C Guandalini, S Lavietes, M Mignosa, P Rose, A Syme, W Tamborlane, S Edelstein, P Feit, N Grover, C Long, L Pyle, B Linder, S Marcovina, J Chmielewski, M Ramirez, G Strylewicz, J Shepherd, B Fan, L Marquez, M Sherman, J Wang, E Mayer-Davis, Y Liu, M Nichols, D Wilfley, D Aldrich-Rasche, K Franklin, D Laughlin, G Leibach, C Massmann, M Mills, D O'Brien, J Patterson, T Tibbs, D Van Buren, A Vannuci, P Zhang, M Palmert, L Epstein, J Silverstein
Abstract
Background: TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) is a federally funded multicenter randomized clinical trial comparing three treatments of youth onset type 2 diabetes.
Objective: To describe the experience of youth participating in a 2-6 month run-in period in preparation for randomization into TODAY.
Subjects: An ethnically diverse sample of 927 youth, 65.4% females, aged 13.7 ± 2.0 yr old, with type 2 diabetes for a median of 2 months (0.7-7.8 months, 25th-75th percentiles).
Methods: A run-in period was conducted to achieve HbA1c <8% with metformin monotherapy and diabetes education, and to evaluate adherence to pill taking, visit attendance, and other procedures.
Results: At entry, mean body mass index (BMI) and z-BMI were 35.6 ± 7.7 and 2.3 ± 0.4, respectively, mean HbA1c was 7.7 ± 2.2%, only 42.5% were on a hypoglycemic treatment, and 35.6% had HbA1c ≥8%. Comorbid conditions were common; 18.8% had hypertension, 24.2% had elevated cholesterol, and 6.5% had abnormal liver enzymes. After a median 71 d of run-in, 90.9% had HbA1c <8%, 77.9% had HbA1c <7%, and 46.4% had HbA1c <6%. Of the 772 youth achieving the target HbA1c <8%, 704 (91.2%) were randomized; non-adherence to metformin treatment was the main cause for non-randomization. Youth proceeding to randomization decreased weight by 0.68 kg and HbA1c by 1.45% compared to a weight gain of 0.71 kg and HbA1c decrease of 0.74% in the non-randomized youth (p = 0.01 in both cases). However, change in z-BMI was not significantly different between the two groups.
Conclusions: Most youth with recent onset type 2 diabetes can achieve target HbA1c <8.0% with short-term metformin monotherapy and standard diabetes education (ClinicalTrials.gov identifier: NCT00081328).
Conflict of interest statement
Members of the writing group have no conflicts of interest or financial arrangements to disclose.
© 2012 John Wiley & Sons A/S.
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Source: PubMed