A Clinical Trial to Maintain Glycemic Control in Youth with Type 2 Diabetes

被引:684
作者
Zeitler, Phil [1 ]
Hirst, Kathryn [2 ]
Pyle, Laura [2 ]
Linder, Barbara [3 ]
Copeland, Kenneth [4 ]
Arslanian, Silva [5 ]
Cuttler, Leona [6 ]
Nathan, David M. [7 ]
Tollefsen, Sherida [8 ]
Wilfley, Denise [9 ]
Kaufman, Francine [10 ]
机构
[1] Univ Colorado, Denver, CO 80202 USA
[2] George Washington Univ, Washington, DC USA
[3] NIDDK, Bethesda, MD USA
[4] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA
[5] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA
[6] Case Western Reserve Univ, Cleveland, OH 44106 USA
[7] Massachusetts Gen Hosp, Boston, MA 02114 USA
[8] St Louis Univ, St Louis, MO 63103 USA
[9] Washington Univ, St Louis, MO 63130 USA
[10] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA
关键词
OBESE BLACK; INSULIN; ADOLESCENTS; METFORMIN; AMERICAN; MELLITUS; CHILDREN; FAT;
D O I
10.1056/NEJMoa1109333
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND Despite the increasing prevalence of type 2 diabetes in youth, there are few data to guide treatment. We compared the efficacy of three treatment regimens to achieve durable glycemic control in children and adolescents with recent-onset type 2 diabetes. METHODS Eligible patients 10 to 17 years of age were treated with metformin (at a dose of 1000 mg twice daily) to attain a glycated hemoglobin level of less than 8% and were randomly assigned to continued treatment with metformin alone or to metformin combined with rosiglitazone (4 mg twice a day) or a lifestyle-intervention program focusing on weight loss through eating and activity behaviors. The primary outcome was loss of glycemic control, defined as a glycated hemoglobin level of at least 8% for 6 months or sustained metabolic decompensation requiring insulin. RESULTS Of the 699 randomly assigned participants (mean duration of diagnosed type 2 diabetes, 7.8 months), 319 (45.6%) reached the primary outcome over an average follow-up of 3.86 years. Rates of failure were 51.7% (120 of 232 participants), 38.6% (90 of 233), and 46.6% (109 of 234) for metformin alone, metformin plus rosiglitazone, and metformin plus lifestyle intervention, respectively. Metformin plus rosiglitazone was superior to metformin alone (P = 0.006); metformin plus lifestyle intervention was intermediate but not significantly different from metformin alone or metformin plus rosiglitazone. Prespecified analyses according to sex and race or ethnic group showed differences in sustained effectiveness, with metformin alone least effective in non-Hispanic black participants and metformin plus rosiglitazone most effective in girls. Serious adverse events were reported in 19.2% of participants. CONCLUSIONS Monotherapy with metformin was associated with durable glycemic control in approximately half of children and adolescents with type 2 diabetes. The addition of rosiglitazone, but not an intensive lifestyle intervention, was superior to metformin alone. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; TODAY ClinicalTrials.gov number, NCT00081328.)
引用
收藏
页码:2247 / 2256
页数:10
相关论文
共 20 条
[11]  
Kahn SE, 2007, NEW ENGL J MED, V356, P1387
[12]   The Presence of GAD and IA-2 Antibodies in Youth With a Type 2 Diabetes Phenotype Results from the TODAY study [J].
Klingensmith, Georgeanna J. ;
Pyle, Laura ;
Arslanian, Silva ;
Copeland, Kenneth C. ;
Cuttler, Leona ;
Kaufman, Francine ;
Laffel, Lori ;
Marcovina, Santica ;
Tollefsen, Sherida E. ;
Weinstock, Ruth S. ;
Linder, Barbara .
DIABETES CARE, 2010, 33 (09) :1970-1975
[13]  
Lee S, 2006, DIABETES CARE, V29, P51, DOI 10.2337/diacare.29.01.06.dc05-0952
[14]   The global spread of type 2 diabetes mellitus in children and adolescents [J].
Pinhas-Hamiel, O ;
Zeitler, P .
JOURNAL OF PEDIATRICS, 2005, 146 (05) :693-700
[15]   The type 2 family -: A setting for development and treatment of adolescent type 2 diabetes mellitus [J].
Pinhas-Hamiel, O ;
Standiford, D ;
Hamiel, D ;
Dolan, LM ;
Cohen, R ;
Zeitler, PS .
ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE, 1999, 153 (10) :1063-1067
[16]   Clinical presentation and treatment of type 2 diabetes in children [J].
Pinhas-Hamiel, Orit ;
Zeitler, Phil .
PEDIATRIC DIABETES, 2007, 8 :16-27
[17]  
Pinhas-Hamiel Orit, 2003, Pediatr Diabetes, V4, P24, DOI 10.1034/j.1399-5448.2003.00027.x
[18]   Design of a family-based lifestyle intervention for youth with type 2 diabetes: the TODAY study The TODAY Study Group [J].
Wilfley, D. E. ;
Haymond, M. ;
Anderson, B. ;
Gunn, S. ;
Holden, H. ;
Jones, M. ;
Hwu, K. ;
McGirk, S. ;
Mckay, S. ;
Schreiner, B. ;
Cuttler, L. ;
Abrams, E. ;
Casey, T. ;
Dahms, W. ;
Drotar, D. ;
Huestis, S. ;
Levers-Landis, C. ;
McGuigan, P. ;
Sundararajan, S. ;
Geffner, M. ;
Chang, N. ;
Dreimane, D. ;
Halvorson, M. ;
Hernandez, S. ;
Kaufman, F. ;
Mansilla, V. ;
Ortiz, R. ;
Ward, A. ;
Wexler, K. ;
Yasuda, P. ;
Katz, L. Levitt ;
Berkowitz, R. ;
Boyd, S. ;
Carchidi, C. ;
Kaplan, J. ;
Keating, C. ;
Kneeshaw-Price, S. ;
Lassiter, C. ;
Lipman, T. ;
Magge, S. ;
McGinley, G. ;
Schwartzman, B. ;
Willi, S. ;
Arslanian, S. ;
Bacha, F. ;
Foster, S. ;
Galvin, B. ;
Hannon, T. ;
Kriska, A. ;
Libman, I. .
INTERNATIONAL JOURNAL OF OBESITY, 2010, 34 (02) :217-226
[19]   United Kingdom prospective diabetes study 17: A 9-year update of a randomized, controlled trial on the effect of improved metabolic control on complications in non-insulin-dependent diabetes mellitus [J].
Turner, R ;
Cull, C ;
Holman, R .
ANNALS OF INTERNAL MEDICINE, 1996, 124 (01) :136-145
[20]   Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus - Progressive requirement for multiple therapies (UKPDS 49) [J].
Turner, RC ;
Cull, CA ;
Frighi, V ;
Holman, RR .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1999, 281 (21) :2005-2012