Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY)

NCT00081328 | Completed Phase 3 Results DMC

• 2 other identifiers: IND - DK61230-TODAYU01DK061230
• Study Type: interventional
• Target: 699
• Locations: 1 country
• Sites: 16

Brief Summary

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) has sponsored a consortium of investigators to conduct a clinical treatment trial, Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY). The primary objective of the TODAY trial is to compare the efficacy of three treatment arms on time to treatment failure based on glycemic control. The secondary aims are to:

• compare and evaluate the safety of the three treatment arms;
• compare the effects of the three treatments on the pathophysiology of type 2 diabetes (T2D) with regards to beta cell function and insulin resistance, body composition, nutrition, physical activity and aerobic fitness, cardiovascular risk factors, microvascular complications, quality of life, and psychological outcomes;
• evaluate the influence of individual and family behaviors on treatment response; and
• compare the relative cost effectiveness of the three treatment arms. The three treatment regimens are: (1) metformin alone, (2) metformin plus rosiglitazone, and (3) metformin plus an intensive lifestyle intervention called the TODAY Lifestyle Program (TLP). The study recruits patients over a three-year period and follows patients for a minimum of two years. Patients are randomized within two years of the diagnosis of T2D.

Conditions

Diabetes Mellitus, Type II

Outcome Measures

Primary Outcomes (1)

• Treatment Failure (Loss of Glycemic Control)

  Defined as A1c persistently \>=8% over a 6-month period or persistent metabolic decompensation (inability to wean insulin within 3 months of initiation or the occurrence of a second episode within three months of discontinuing insulin)

  Study duration - 2 years to 6.5 years of follow up from randomization

Secondary Outcomes (10)

• Insulin Sensitivity

  24 months

• Number of Serious Adverse Events

  Reported as occurred during study follow-up - 2 years to 6.5 years from randomization.

• Insulin Secretion

  24 months

• Body Composition -- BMI

  24 months

• Body Composition -- Waist Circumference

  24 months

Study Arms (3)

1

EXPERIMENTAL

Metformin alone

Drug: Metformin

2

EXPERIMENTAL

Metformin + Rosiglitazone

Drug: Metformin; Drug: Rosiglitazone

3

EXPERIMENTAL

Metformin + Lifestyle Program

Drug: Metformin; Behavioral: Lifestyle Program

Interventions

Metformin DRUG

capsule, 1000 mg bid

1; 2; 3

Rosiglitazone DRUG

capsule, 4 mg bid

2

Lifestyle Program BEHAVIORAL

a lifestyle change (LC) phase of weekly sessions for months 1-6, followed by a bi-weekly lifestyle maintenance (LM) phase through months 7-12, and a continued contact (CC) phase from months 13 through the end of the study. The CC phase sessions are scheduled monthly for the initial 12 months (study months 13-24) and then quarterly or 4 times a year to the end of the study

3

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Diabetes by ADA criteria (laboratory determinations of fasting glucose ≥ 126 mg/dL, random glucose ≥ 200 mg/dL, or two-hour OGTT glucose ≥ 200 mg/dL) documented and confirmed in medical record. For patients diagnosed with diabetes during screening who have a normal fasting glucose but an elevated two-hour glucose during an OGTT, the HbA1c must be ≥ 6%.
• Duration since diagnosis less than two years by date of randomization.
• BMI ≥ 85th percentile documented at time of diagnosis or at screening.
• Fasting C-peptide at screening (drawn at least one week after treatment for ketosis or acidosis, if applicable) \> 0.6 ng/mL.
• Absence of pancreatic autoimmunity (both GAD and ICA512 negative).
• Age 10-17, with randomization prior to 18th birthday.
• Signed informed consent/assent forms for the pre-randomization period.
• A family member or adult closely involved in the daily activities of the child agrees to participate in the child's treatment.
• Fluency in English or Spanish for both child and family member.
• Patient and family able to fully participate in trial protocol in the opinion of the investigator.

You may not qualify if:

• Participating in another interventional research study protocol in the past 30 days.
• Genetic syndrome or disorder known to affect glucose tolerance other than diabetes.
• Patient on inhaled steroids at dose above 1000 mcg daily Flovent equivalent.
• Patient on a course of oral steroids within the last 60 days or on oral steroids more than 20 days during the past year.
• Patient on medication(s) that are known to affect insulin sensitivity or secretion within the last 30 days.
• Patient on medication(s) that are known to cause weight gain within the last 30 days.
• Patient on any weight-loss medication(s) within the last 30 days.
• Patient on medication(s) known to affect the metabolism of study drug.
• Inability to comprehend the lowest grade level at which lifestyle intervention materials are prepared, for both child and participating family member.
• Females who are pregnant, planning to become pregnant within two years of enrollment, or who admit sexual activity without appropriate contraception.
• Calculated creatinine clearance \< 70 mL/min.
• Any transaminase \> 2.5 ULN. If any transaminase 1.5-2.5 times ULN, then patient must be appropriately evaluated by PCP (minimum evaluation includes ceruloplasmin level, alpha-1 antitrypsin phenotype, ANA, anti-smooth muscle antibody, anti-LKM antibody, anti-HCV, and anti-HBc total antibody not IgM, iron, and TIBC) and is eligible if all other causes for elevation are ruled out and it is presumed due only to non-alcoholic fatty liver disease (NAFLD).
• Diabetic ketoacidosis (DKA) at any time after diagnosis unless only a single episode of DKA related to a significant medical illness.
• Physical limitations preventing patient from being randomized to the lifestyle intervention.
• Patient plans to leave the geographic area within one calendar year.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (16)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of Colorado Health Sciences Center, The Children's Hospital

Denver, Colorado, 80262, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

George Washington University Biostatistics Center

Rockville, Maryland, 20852, United States

Location

Massachusetts General Hospital Diabetes Center

Boston, Massachusetts, 02114, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

Saint Louis University Health Sciences Center

St Louis, Missouri, 63104, United States

Location

Washington University Department of Pediatrics

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

Location

Case Western Reserve

Cleveland, Ohio, 44106, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 93104, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Related Publications (79)

• TODAY Study Group; Zeitler P, Epstein L, Grey M, Hirst K, Kaufman F, Tamborlane W, Wilfley D. Treatment options for type 2 diabetes in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes. Pediatr Diabetes. 2007 Apr;8(2):74-87. doi: 10.1111/j.1399-5448.2007.00237.x.

  PMID: 17448130 BACKGROUND

• Songer T, Glazner J, Coombs LP, Cuttler L, Daniel M, Estrada S, Klingensmith G, Kriska A, Laffel L, Zhang P; the TODAY Study Group. Examining the economic costs related to lifestyle and pharmacological interventions in youth with Type 2 diabetes. Expert Rev Pharmacoecon Outcomes Res. 2006 Jun 1;6(3):315-324. doi: 10.1586/14737167.6.3.315.

  PMID: 19774104 BACKGROUND

• Grey M, Schreiner B, Pyle L. Development of a diabetes education program for youth with type 2 diabetes. Diabetes Educ. 2009 Jan-Feb;35(1):108-16. doi: 10.1177/0145721708325156.

  PMID: 19244566 BACKGROUND

• TODAY Study Group. Design of a family-based lifestyle intervention for youth with type 2 diabetes: the TODAY study. Int J Obes (Lond). 2010 Feb;34(2):217-26. doi: 10.1038/ijo.2009.195. Epub 2009 Oct 13.

  PMID: 19823189 BACKGROUND

• Larkin ME, McGuigan P, Richards D, Blumenthal K, Milaszewski K, Higgins L, Schanuel J, Long C. Collaborative Staffing Model for Multiple Sites: Reducing the challenges of study coordination in complex, multi-site clinical trials. Appl Clin Trials. 2011 Jan 1;20(1):30-35.

  PMID: 24955003 BACKGROUND

• Chadwick JQ, Copeland KC, Daniel MR, Erb-Alvarez JA, Felton BA, Khan SI, Saunkeah BR, Wharton DF, Payan ML. Partnering in research: a national research trial exemplifying effective collaboration with American Indian Nations and the Indian Health Service. Am J Epidemiol. 2014 Dec 15;180(12):1202-7. doi: 10.1093/aje/kwu246. Epub 2014 Nov 11.

  PMID: 25389367 BACKGROUND

• Chadwick JQ, Van Buren DJ, Morales E, Timpson A, Abrams EL, Syme A, Preske J, Mireles G, Anderson B, Grover N, Laffel L. Structure to utilize interventionists' implementation experiences of a family-based behavioral weight management program to enhance the dissemination of the standardized intervention: The TODAY study. Clin Trials. 2017 Aug;14(4):406-412. doi: 10.1177/1740774517707727. Epub 2017 May 9.

  PMID: 28486851 BACKGROUND

• Chadwick JQ, Copeland KC, Branam DE, Erb-Alvarez JA, Khan SI, Peercy MT, Rogers ME, Saunkeah BR, Tryggestad JB, Wharton DF. Genomic Research and American Indian Tribal Communities in Oklahoma: Learning From Past Research Misconduct and Building Future Trusting Partnerships. Am J Epidemiol. 2019 Jul 1;188(7):1206-1212. doi: 10.1093/aje/kwz062.

  PMID: 31081852 BACKGROUND

• Songer TJ, Haymond MW, Glazner JE, Klingensmith GJ, Laffel LM, Zhang P, Hirst K; TODAY Study Group. Healthcare and associated costs related to type 2 diabetes in youth and adolescence: the TODAY clinical trial experience. Pediatr Diabetes. 2019 Sep;20(6):702-711. doi: 10.1111/pedi.12869. Epub 2019 Jun 6.

  PMID: 31119838 BACKGROUND

• Klingensmith GJ, Pyle L, Arslanian S, Copeland KC, Cuttler L, Kaufman F, Laffel L, Marcovina S, Tollefsen SE, Weinstock RS, Linder B; TODAY Study Group. The presence of GAD and IA-2 antibodies in youth with a type 2 diabetes phenotype: results from the TODAY study. Diabetes Care. 2010 Sep;33(9):1970-5. doi: 10.2337/dc10-0373. Epub 2010 Jun 2.

  PMID: 20519658 RESULT

• Copeland KC, Zeitler P, Geffner M, Guandalini C, Higgins J, Hirst K, Kaufman FR, Linder B, Marcovina S, McGuigan P, Pyle L, Tamborlane W, Willi S; TODAY Study Group. Characteristics of adolescents and youth with recent-onset type 2 diabetes: the TODAY cohort at baseline. J Clin Endocrinol Metab. 2011 Jan;96(1):159-67. doi: 10.1210/jc.2010-1642. Epub 2010 Oct 20.

  PMID: 20962021 RESULT

• TODAY Study Group; Wilfley D, Berkowitz R, Goebel-Fabbri A, Hirst K, Ievers-Landis C, Lipman TH, Marcus M, Ng D, Pham T, Saletsky R, Schanuel J, Van Buren D. Binge eating, mood, and quality of life in youth with type 2 diabetes: baseline data from the today study. Diabetes Care. 2011 Apr;34(4):858-60. doi: 10.2337/dc10-1704. Epub 2011 Feb 28.

  PMID: 21357794 RESULT

• Anderson BJ, Edelstein S, Abramson NW, Katz LE, Yasuda PM, Lavietes SJ, Trief PM, Tollefsen SE, McKay SV, Kringas P, Casey TL, Marcus MD. Depressive symptoms and quality of life in adolescents with type 2 diabetes: baseline data from the TODAY study. Diabetes Care. 2011 Oct;34(10):2205-7. doi: 10.2337/dc11-0431. Epub 2011 Aug 11.

  PMID: 21836107 RESULT

• Laffel L, Chang N, Grey M, Hale D, Higgins L, Hirst K, Izquierdo R, Larkin M, Macha C, Pham T, Wauters A, Weinstock RS; TODAY Study Group. Metformin monotherapy in youth with recent onset type 2 diabetes: experience from the prerandomization run-in phase of the TODAY study. Pediatr Diabetes. 2012 Aug;13(5):369-75. doi: 10.1111/j.1399-5448.2011.00846.x. Epub 2012 Feb 27.

  PMID: 22369102 RESULT

• Bacha F, Pyle L, Nadeau K, Cuttler L, Goland R, Haymond M, Levitsky L, Lynch J, Weinstock RS, White NH, Caprio S, Arslanian S; TODAY Study Group. Determinants of glycemic control in youth with type 2 diabetes at randomization in the TODAY study. Pediatr Diabetes. 2012 Aug;13(5):376-83. doi: 10.1111/j.1399-5448.2011.00841.x. Epub 2012 Feb 15.

  PMID: 22332798 RESULT

• TODAY Study Group; Zeitler P, Hirst K, Pyle L, Linder B, Copeland K, Arslanian S, Cuttler L, Nathan DM, Tollefsen S, Wilfley D, Kaufman F. A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med. 2012 Jun 14;366(24):2247-56. doi: 10.1056/NEJMoa1109333. Epub 2012 Apr 29.

  PMID: 22540912 RESULT

• Kriska A, Delahanty L, Edelstein S, Amodei N, Chadwick J, Copeland K, Galvin B, El ghormli L, Haymond M, Kelsey M, Lassiter C, Mayer-Davis E, Milaszewski K, Syme A. Sedentary behavior and physical activity in youth with recent onset of type 2 diabetes. Pediatrics. 2013 Mar;131(3):e850-6. doi: 10.1542/peds.2012-0620. Epub 2013 Feb 11.

  PMID: 23400602 RESULT

• Delahanty L, Kriska A, Edelstein S, Amodei N, Chadwick J, Copeland K, Galvin B, El Ghormli L, Haymond M, Kelsey MM, Lassiter C, Milaszewski K, Syme A, Mayer-Davis E. Self-reported dietary intake of youth with recent onset of type 2 diabetes: results from the TODAY study. J Acad Nutr Diet. 2013 Mar;113(3):431-439. doi: 10.1016/j.jand.2012.11.015.

  PMID: 23438494 RESULT

• TODAY Study Group. Rapid rise in hypertension and nephropathy in youth with type 2 diabetes: the TODAY clinical trial. Diabetes Care. 2013 Jun;36(6):1735-41. doi: 10.2337/dc12-2420.

  PMID: 23704672 RESULT

• TODAY Study Group. Treatment effects on measures of body composition in the TODAY clinical trial. Diabetes Care. 2013 Jun;36(6):1742-8. doi: 10.2337/dc12-2534.

  PMID: 23704673 RESULT

• TODAY Study Group. Effects of metformin, metformin plus rosiglitazone, and metformin plus lifestyle on insulin sensitivity and beta-cell function in TODAY. Diabetes Care. 2013 Jun;36(6):1749-57. doi: 10.2337/dc12-2393.

  PMID: 23704674 RESULT

• TODAY Study Group. Lipid and inflammatory cardiovascular risk worsens over 3 years in youth with type 2 diabetes: the TODAY clinical trial. Diabetes Care. 2013 Jun;36(6):1758-64. doi: 10.2337/dc12-2388.

  PMID: 23704675 RESULT

• TODAY Study Group. Safety and tolerability of the treatment of youth-onset type 2 diabetes: the TODAY experience. Diabetes Care. 2013 Jun;36(6):1765-71. doi: 10.2337/dc12-2390.

  PMID: 23704676 RESULT

• TODAY Study Group. Retinopathy in youth with type 2 diabetes participating in the TODAY clinical trial. Diabetes Care. 2013 Jun;36(6):1772-4. doi: 10.2337/dc12-2387.

  PMID: 23704677 RESULT

• Levitt Katz L, Gidding SS, Bacha F, Hirst K, McKay S, Pyle L, Lima JA; TODAY Study Group. Alterations in left ventricular, left atrial, and right ventricular structure and function to cardiovascular risk factors in adolescents with type 2 diabetes participating in the TODAY clinical trial. Pediatr Diabetes. 2015 Feb;16(1):39-47. doi: 10.1111/pedi.12119. Epub 2014 Jan 22.

  PMID: 24450390 RESULT

• Narasimhan S, Weinstock RS. Youth-onset type 2 diabetes mellitus: lessons learned from the TODAY study. Mayo Clin Proc. 2014 Jun;89(6):806-16. doi: 10.1016/j.mayocp.2014.01.009. Epub 2014 Apr 3.

  PMID: 24702733 RESULT

• Walders-Abramson N, Venditti EM, Ievers-Landis CE, Anderson B, El Ghormli L, Geffner M, Kaplan J, Koontz MB, Saletsky R, Payan M, Yasuda P; Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study Group. Relationships among stressful life events and physiological markers, treatment adherence, and psychosocial functioning among youth with type 2 diabetes. J Pediatr. 2014 Sep;165(3):504-508.e1. doi: 10.1016/j.jpeds.2014.05.020. Epub 2014 Jun 16.

  PMID: 24948348 RESULT

• Tryggestad JB, Willi SM. Complications and comorbidities of T2DM in adolescents: findings from the TODAY clinical trial. J Diabetes Complications. 2015 Mar;29(2):307-12. doi: 10.1016/j.jdiacomp.2014.10.009. Epub 2014 Oct 29.

  PMID: 25468310 RESULT

• Weinstock RS, Trief PM, El Ghormli L, Goland R, McKay S, Milaszewski K, Preske J, Willi S, Yasuda PM. Parental Characteristics Associated With Outcomes in Youth With Type 2 Diabetes: Results From the TODAY Clinical Trial. Diabetes Care. 2015 May;38(5):784-92. doi: 10.2337/dc14-2393. Epub 2015 Mar 17.

  PMID: 25784663 RESULT

• Weinstock RS, Drews KL, Caprio S, Leibel NI, McKay SV, Zeitler PS; TODAY Study Group. Metabolic syndrome is common and persistent in youth-onset type 2 diabetes: Results from the TODAY clinical trial. Obesity (Silver Spring). 2015 Jul;23(7):1357-61. doi: 10.1002/oby.21120. Epub 2015 Jun 5.

  PMID: 26047470 RESULT

• Ievers-Landis CE, Walders-Abramson N, Amodei N, Drews KL, Kaplan J, Levitt Katz LE, Lavietes S, Saletsky R, Seidman D, Yasuda P; Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study Group. Longitudinal Correlates of Health Risk Behaviors in Children and Adolescents with Type 2 Diabetes. J Pediatr. 2015 May;166(5):1258-1264.e3. doi: 10.1016/j.jpeds.2015.01.019. Epub 2015 Feb 20.

  PMID: 25702853 RESULT

• Larkin ME, Walders-Abramson N, Hirst K, Keady J, Ievers-Landis CE, Venditti EM, Yasuda PM. Effects of comorbid conditions on health-related quality of life in youth with Type 2 diabetes: the TODAY clinical trial. Diabetes Manag (Lond). 2015 Nov;5(6):431-439. doi: 10.2217/dmt.15.35.

  PMID: 27057209 RESULT

• Zeitler P, Hirst K, Copeland KC, El Ghormli L, Levitt Katz L, Levitsky LL, Linder B, McGuigan P, White NH, Wilfley D; TODAY Study Group. HbA1c After a Short Period of Monotherapy With Metformin Identifies Durable Glycemic Control Among Adolescents With Type 2 Diabetes. Diabetes Care. 2015 Dec;38(12):2285-92. doi: 10.2337/dc15-0848. Epub 2015 Nov 4.

  PMID: 26537182 RESULT

• Walders-Abramson N, Anderson B, Larkin ME, Chang N, Venditti E, Bzdick S, Tryggestad JB, Tan K, Geffner ME, Hirst K. Benefits and barriers to participating in longitudinal research of youth-onset type 2 diabetes: Results from the TODAY retention survey. Clin Trials. 2016 Apr;13(2):240-3. doi: 10.1177/1740774515613949. Epub 2015 Nov 3.

  PMID: 26531295 RESULT

• Chernausek SD, Arslanian S, Caprio S, Copeland KC, El ghormli L, Kelsey MM, Koontz MB, Orsi CM, Wilfley D. Relationship Between Parental Diabetes and Presentation of Metabolic and Glycemic Function in Youth With Type 2 Diabetes: Baseline Findings From the TODAY Trial. Diabetes Care. 2016 Jan;39(1):110-7. doi: 10.2337/dc15-1557. Epub 2015 Nov 17.

  PMID: 26577415 RESULT

• Klingensmith GJ, Pyle L, Nadeau KJ, Barbour LA, Goland RS, Willi SM, Linder B, White NH; TODAY Study Group. Pregnancy Outcomes in Youth With Type 2 Diabetes: The TODAY Study Experience. Diabetes Care. 2016 Jan;39(1):122-9. doi: 10.2337/dc15-1206. Epub 2015 Dec 1.

  PMID: 26628417 RESULT

• Kelsey MM, Geffner ME, Guandalini C, Pyle L, Tamborlane WV, Zeitler PS, White NH; Treatment Options for Type 2 Diabetes in Adolescents and Youth Study Group. Presentation and effectiveness of early treatment of type 2 diabetes in youth: lessons from the TODAY study. Pediatr Diabetes. 2016 May;17(3):212-21. doi: 10.1111/pedi.12264. Epub 2015 Feb 17.

  PMID: 25690268 RESULT

• Rockette-Wagner B, Storti KL, Edelstein S, Delahanty LM, Galvin B, Jackson A, Kriska AM. Measuring Physical Activity and Sedentary Behavior in Youth with Type 2 Diabetes. Child Obes. 2017 Feb;13(1):72-77. doi: 10.1089/chi.2015.0151. Epub 2016 Feb 9.

  PMID: 26859798 RESULT

• Arslanian S, El Ghormli L, Bacha F, Caprio S, Goland R, Haymond MW, Levitsky L, Nadeau KJ, White NH, Willi SM; TODAY Study Group. Adiponectin, Insulin Sensitivity, beta-Cell Function, and Racial/Ethnic Disparity in Treatment Failure Rates in TODAY. Diabetes Care. 2017 Jan;40(1):85-93. doi: 10.2337/dc16-0455. Epub 2016 Nov 1.

  PMID: 27803118 RESULT

• Marcus MD, Wilfley DE, El Ghormli L, Zeitler P, Linder B, Hirst K, Ievers-Landis CE, van Buren DJ, Walders-Abramson N; TODAY Study Group. Weight change in the management of youth-onset type 2 diabetes: the TODAY clinical trial experience. Pediatr Obes. 2017 Aug;12(4):337-345. doi: 10.1111/ijpo.12148. Epub 2016 May 10.

  PMID: 27161901 RESULT

• Gandica R, Zeitler P. Update on Youth-Onset Type 2 Diabetes: Lessons Learned from the Treatment Options for Type 2 Diabetes in Adolescents and Youth Clinical Trial. Adv Pediatr. 2016 Aug;63(1):195-209. doi: 10.1016/j.yapd.2016.04.013. Epub 2016 Jun 3. No abstract available.

  PMID: 27426901 RESULT

• Katz LL, Anderson BJ, McKay SV, Izquierdo R, Casey TL, Higgins LA, Wauters A, Hirst K, Nadeau KJ; TODAY Study Group. Correlates of Medication Adherence in the TODAY Cohort of Youth With Type 2 Diabetes. Diabetes Care. 2016 Nov;39(11):1956-1962. doi: 10.2337/dc15-2296. Epub 2016 Jun 28.

  PMID: 27352955 RESULT

• Bacha F, Gidding SS, Pyle L, Levitt Katz L, Kriska A, Nadeau KJ, Lima JAC; Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study Group. Relationship of Cardiac Structure and Function to Cardiorespiratory Fitness and Lean Body Mass in Adolescents and Young Adults with Type 2 Diabetes. J Pediatr. 2016 Oct;177:159-166.e1. doi: 10.1016/j.jpeds.2016.06.048. Epub 2016 Aug 4.

  PMID: 27499218 RESULT

• Kriska A, El Ghormli L, Copeland KC, Higgins J, Ievers-Landis CE, Levitt Katz LE, Trief PM, Wauters AD, Yasuda PM, Delahanty LM; TODAY Study Group. Impact of lifestyle behavior change on glycemic control in youth with type 2 diabetes. Pediatr Diabetes. 2018 Feb;19(1):36-44. doi: 10.1111/pedi.12526. Epub 2017 Apr 4.

  PMID: 28378429 RESULT

• Berkowitz RI, Marcus MD, Anderson BJ, Delahanty L, Grover N, Kriska A, Laffel L, Syme A, Venditti E, Van Buren DJ, Wilfley DE, Yasuda P, Hirst K; TODAY Study Group. Adherence to a lifestyle program for youth with type 2 diabetes and its association with treatment outcome in the TODAY clinical trial. Pediatr Diabetes. 2018 Mar;19(2):191-198. doi: 10.1111/pedi.12555. Epub 2017 Jun 30.

  PMID: 28664624 RESULT

• Bjornstad P, Nehus E, El Ghormli L, Bacha F, Libman IM, McKay S, Willi SM, Laffel L, Arslanian S, Nadeau KJ; TODAY Study Group. Insulin Sensitivity and Diabetic Kidney Disease in Children and Adolescents With Type 2 Diabetes: An Observational Analysis of Data From the TODAY Clinical Trial. Am J Kidney Dis. 2018 Jan;71(1):65-74. doi: 10.1053/j.ajkd.2017.07.015. Epub 2017 Nov 20.

  PMID: 29157731 RESULT

• Gidding SS, Bacha F, Bjornstad P, Levitt Katz LE, Levitsky LL, Lynch J, Tryggestad JB, Weinstock RS, El Ghormli L, Lima JAC; TODAY Study Group. Cardiac Biomarkers in Youth with Type 2 Diabetes Mellitus: Results from the TODAY Study. J Pediatr. 2018 Jan;192:86-92.e5. doi: 10.1016/j.jpeds.2017.09.012.

  PMID: 29246363 RESULT

• Kleinberger JW, Copeland KC, Gandica RG, Haymond MW, Levitsky LL, Linder B, Shuldiner AR, Tollefsen S, White NH, Pollin TI. Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial. Genet Med. 2018 Jun;20(6):583-590. doi: 10.1038/gim.2017.150. Epub 2017 Oct 12.

  PMID: 29758564 RESULT

• Van Buren DJ, Wilfley DE, Marcus MD, Anderson B, Abramson NW, Berkowitz R, Ievers-Landis C, Trief P, Yasuda P, Hirst K; TODAY Study Group. Depressive symptoms and glycemic control in youth with type 2 diabetes participating in the TODAY clinical trial. Diabetes Res Clin Pract. 2018 Jan;135:85-87. doi: 10.1016/j.diabres.2017.11.008. Epub 2017 Nov 13.

  PMID: 29146120 RESULT

• Levitt Katz LE, Bacha F, Gidding SS, Weinstock RS, El Ghormli L, Libman I, Nadeau KJ, Porter K, Marcovina S; TODAY Study Group. Lipid Profiles, Inflammatory Markers, and Insulin Therapy in Youth with Type 2 Diabetes. J Pediatr. 2018 May;196:208-216.e2. doi: 10.1016/j.jpeds.2017.12.052. Epub 2018 Feb 2.

  PMID: 29398050 RESULT

• Inge TH, Laffel LM, Jenkins TM, Marcus MD, Leibel NI, Brandt ML, Haymond M, Urbina EM, Dolan LM, Zeitler PS; Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) and Treatment Options of Type 2 Diabetes in Adolescents and Youth (TODAY) Consortia. Comparison of Surgical and Medical Therapy for Type 2 Diabetes in Severely Obese Adolescents. JAMA Pediatr. 2018 May 1;172(5):452-460. doi: 10.1001/jamapediatrics.2017.5763.

  PMID: 29532078 RESULT

• Venditti EM, Tan K, Chang N, Laffel L, McGinley G, Miranda N, Tryggestad JB, Walders-Abramson N, Yasuda P, Delahanty L; TODAY Study Group. Barriers and strategies for oral medication adherence among children and adolescents with Type 2 diabetes. Diabetes Res Clin Pract. 2018 May;139:24-31. doi: 10.1016/j.diabres.2018.02.001. Epub 2018 Feb 8.

  PMID: 29427697 RESULT

• Kelsey MM, Braffett BH, Geffner ME, Levitsky LL, Caprio S, McKay SV, Shah R, Sprague JE, Arslanian SA; TODAY Study Group. Menstrual Dysfunction in Girls From the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study. J Clin Endocrinol Metab. 2018 Jun 1;103(6):2309-2318. doi: 10.1210/jc.2018-00132.

  PMID: 29697830 RESULT

• Shah AS, El Ghormli L, Gidding SS, Bacha F, Nadeau KJ, Levitt Katz LE, Tryggestad JB, Leibel N, Hale DE, Urbina EM. Prevalence of arterial stiffness in adolescents with type 2 diabetes in the TODAY cohort: Relationships to glycemic control and other risk factors. J Diabetes Complications. 2018 Aug;32(8):740-745. doi: 10.1016/j.jdiacomp.2018.05.013. Epub 2018 May 25.

  PMID: 29936086 RESULT

• Arslanian S, El Ghormli L, Young Kim J, Bacha F, Chan C, Ismail HM, Levitt Katz LE, Levitsky L, Tryggestad JB, White NH; TODAY Study Group. The Shape of the Glucose Response Curve During an Oral Glucose Tolerance Test: Forerunner of Heightened Glycemic Failure Rates and Accelerated Decline in beta-Cell Function in TODAY. Diabetes Care. 2019 Jan;42(1):164-172. doi: 10.2337/dc18-1122. Epub 2018 Nov 19.

  PMID: 30455329 RESULT

• Weinstock RS, Braffett BH, McGuigan P, Larkin ME, Grover NB, Walders-Abramson N, Laffel LM, Chan CL, Chang N, Schwartzman BE, Barajas RA, Celona-Jacobs N, Haymond MW; TODAY Study Group. Self-Monitoring of Blood Glucose in Youth-Onset Type 2 Diabetes: Results From the TODAY Study. Diabetes Care. 2019 May;42(5):903-909. doi: 10.2337/dc18-1854. Epub 2019 Mar 4.

  PMID: 30833375 RESULT

• Bjornstad P, Laffel L, Lynch J, El Ghormli L, Weinstock RS, Tollefsen SE, Nadeau KJ; TODAY Study Group. Elevated Serum Uric Acid Is Associated With Greater Risk for Hypertension and Diabetic Kidney Diseases in Obese Adolescents With Type 2 Diabetes: An Observational Analysis From the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study. Diabetes Care. 2019 Jun;42(6):1120-1128. doi: 10.2337/dc18-2147. Epub 2019 Apr 9.

  PMID: 30967435 RESULT

• Dhaliwal R, Shepherd JA, El Ghormli L, Copeland KC, Geffner ME, Higgins J, Levitsky LL, Nadeau KJ, Weinstock RS, White NH; TODAY Study Group. Changes in Visceral and Subcutaneous Fat in Youth With Type 2 Diabetes in the TODAY Study. Diabetes Care. 2019 Aug;42(8):1549-1559. doi: 10.2337/dc18-1935. Epub 2019 Jun 5.

  PMID: 31167889 RESULT

• Bacha F, El Ghormli L, Arslanian S, Zeitler P, Laffel LM, Levitt Katz LE, Gandica R, Chang NT, Sprague JE, Macleish SA; TODAY Study Group. Predictors of response to insulin therapy in youth with poorly-controlled type 2 diabetes in the TODAY trial. Pediatr Diabetes. 2019 Nov;20(7):871-879. doi: 10.1111/pedi.12906. Epub 2019 Aug 27.

  PMID: 31418516 RESULT

• Shah AS, El Ghormli L, Vajravelu ME, Bacha F, Farrell RM, Gidding SS, Levitt Katz LE, Tryggestad JB, White NH, Urbina EM. Heart Rate Variability and Cardiac Autonomic Dysfunction: Prevalence, Risk Factors, and Relationship to Arterial Stiffness in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study. Diabetes Care. 2019 Nov;42(11):2143-2150. doi: 10.2337/dc19-0993. Epub 2019 Sep 9.

  PMID: 31501226 RESULT

• Bjornstad P, Hughan K, Kelsey MM, Shah AS, Lynch J, Nehus E, Mitsnefes M, Jenkins T, Xu P, Xie C, Inge T, Nadeau K. Effect of Surgical Versus Medical Therapy on Diabetic Kidney Disease Over 5 Years in Severely Obese Adolescents With Type 2 Diabetes. Diabetes Care. 2020 Jan;43(1):187-195. doi: 10.2337/dc19-0708. Epub 2019 Nov 4.

  PMID: 31685489 RESULT

• Shah R, McKay SV, Levitt Katz LE, El Ghormli L, Anderson BJ, Casey TL, Higgins L, Izquierdo R, Wauters AD, Chang N; TODAY Study Group. Adherence to multiple medications in the TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) cohort: effect of additional medications on adherence to primary diabetes medication. J Pediatr Endocrinol Metab. 2020 Feb 25;33(2):191-198. doi: 10.1515/jpem-2019-0315.

  PMID: 31809265 RESULT

• Kaar JL, Schmiege SJ, Drews K, Higgins J, Walders-Abramson N, Isganaitis E, Willi SM, Marcus MD, Zeitler PS, Kelsey MM. Evaluation of the longitudinal change in health behavior profiles across treatment groups in the TODAY clinical trial. Pediatr Diabetes. 2020 Mar;21(2):224-232. doi: 10.1111/pedi.12976. Epub 2020 Jan 6.

  PMID: 31886931 RESULT

• Arslanian S, El Ghormli L, Haymond MH, Chan CL, Chernausek SD, Gandica RG, Gubitosi-Klug R, Levitsky LL, Siska M, Willi SM; TODAY Study Group. Beta cell function and insulin sensitivity in obese youth with maturity onset diabetes of youth mutations vs type 2 diabetes in TODAY: Longitudinal observations and glycemic failure. Pediatr Diabetes. 2020 Jun;21(4):575-585. doi: 10.1111/pedi.12998. Epub 2020 Mar 3.

  PMID: 32064729 RESULT

• Tryggestad JB, Shah RD, Braffett BH, Bacha F, Gidding SS, Gubitosi-Klug RA, Shah AS, Urbina EM, Levitt Katz LE; TODAY Study Group. Circulating adhesion molecules and associations with HbA1c, hypertension, nephropathy, and retinopathy in the Treatment Options for type 2 Diabetes in Adolescent and Youth study. Pediatr Diabetes. 2020 Sep;21(6):923-931. doi: 10.1111/pedi.13062. Epub 2020 Jul 2.

  PMID: 32501612 RESULT

• Ryder JR, Xu P, Nadeau KJ, Kelsey MM, Xie C, Jenkins T, Inge TH, Bjornstad P. Effect of surgical versus medical therapy on estimated cardiovascular event risk among adolescents with type 2 diabetes and severe obesity. Surg Obes Relat Dis. 2021 Jan;17(1):23-33. doi: 10.1016/j.soard.2020.09.002. Epub 2020 Sep 9.

  PMID: 33071178 RESULT

• Levitt Katz LE, El Ghormli LK, Nadeau KJ, Shah A, Higgins J, Kutney K, Gubitosi-Klug R, Burke B, Mokhlesi B; TODAY Study Group. Obstructive sleep apnea, glycemic control, and cardiovascular risk in young adults with youth-onset type 2 diabetes: results from the TODAY study. J Clin Sleep Med. 2025 Nov 1;21(11):1925-1933. doi: 10.5664/jcsm.11784.

  PMID: 40566988 DERIVED

• Nadeau KJ, Arslanian SA, Bacha F, Caprio S, Chao LC, Farrell R, Hughan KS, Rayas M, Tung M, Cross K, El Ghormli L; TODAY Study Group. Insulin clearance at randomisation and in response to treatment in youth with type 2 diabetes: a secondary analysis of the TODAY randomised clinical trial. Diabetologia. 2025 Mar;68(3):676-687. doi: 10.1007/s00125-024-06327-w. Epub 2024 Dec 20.

  PMID: 39706874 DERIVED

• Pyle L, Choi YJ, Narongkiatikhun P, Sharma K, Waikar S, Layton A, Tommerdahl KL, de Boer I, Vigers T, Nelson RG, Lynch J, Brosius F 3rd, Saulnier PJ, Goodrich JA, Tryggestad JB, Isganaitis E, Bacha F, Nadeau KJ, van Raalte D, Kretzler M, Heerspink H, Bjornstad P. Proteomic Analysis Uncovers Multiprotein Signatures Associated with Early Diabetic Kidney Disease in Youth with Type 2 Diabetes Mellitus. Clin J Am Soc Nephrol. 2024 Dec 1;19(12):1603-1612. doi: 10.2215/CJN.0000000000000559. Epub 2024 Oct 21.

  PMID: 39432369 DERIVED

• Lu C, Wolfs D, El Ghormli L, Levitsky LL, Levitt Katz LE, Laffel LM, Patti ME, Isganaitis E. Growth Hormone Mediators and Glycemic Control in Youths With Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024 Feb 5;7(2):e240447. doi: 10.1001/jamanetworkopen.2024.0447.

  PMID: 38421647 DERIVED

• El Ghormli L, Wen H, Uschner D, Haymond MW, Hughan KS, Kutney K, Laffel L, Tollefsen SE, Escaname EN, Lynch J, Bjornstad P; TODAY Study Group. Trajectories of eGFR and risk of albuminuria in youth with type 2 diabetes: results from the TODAY cohort study. Pediatr Nephrol. 2023 Dec;38(12):4137-4144. doi: 10.1007/s00467-023-06044-3. Epub 2023 Jul 11.

  PMID: 37434027 DERIVED

• Levitsky LL, Drews KL, Haymond M, Glubitosi-Klug RA, Levitt Katz LE, Mititelu M, Tamborlane W, Tryggestad JB, Weinstock RS; TODAY Study Group. The obesity paradox: Retinopathy, obesity, and circulating risk markers in youth with type 2 diabetes in the TODAY Study. J Diabetes Complications. 2022 Nov;36(11):108259. doi: 10.1016/j.jdiacomp.2022.108259. Epub 2022 Jul 19.

  PMID: 36150365 DERIVED

• Shah AS, Gidding SS, El Ghormli L, Tryggestad JB, Nadeau KJ, Bacha F, Levitt Katz LE, Willi SM, Lima J, Urbina EM; TODAY Study Group. Relationship between Arterial Stiffness and Subsequent Cardiac Structure and Function in Young Adults with Youth-Onset Type 2 Diabetes: Results from the TODAY Study. J Am Soc Echocardiogr. 2022 Jun;35(6):620-628.e4. doi: 10.1016/j.echo.2022.02.001. Epub 2022 Feb 8.

  PMID: 35149207 DERIVED

• TODAY Study Group; Shah RD, Braffett BH, Tryggestad JB, Hughan KS, Dhaliwal R, Nadeau KJ, Levitt Katz LE, Gidding SS. Cardiovascular risk factor progression in adolescents and young adults with youth-onset type 2 diabetes. J Diabetes Complications. 2022 Mar;36(3):108123. doi: 10.1016/j.jdiacomp.2021.108123. Epub 2022 Jan 3.

  PMID: 35123868 DERIVED

• Trief PM, Uschner D, Tung M, Marcus MD, Rayas M, MacLeish S, Farrell R, Keady J, Chao L, Weinstock RS. Diabetes Distress in Young Adults With Youth-Onset Type 2 Diabetes: TODAY2 Study Results. Diabetes Care. 2022 Mar 1;45(3):529-537. doi: 10.2337/dc21-1689.

  PMID: 35015056 DERIVED

• TODAY Study Group; Shah AS, El Ghormli L, Gidding SS, Hughan KS, Levitt Katz LE, Koren D, Tryggestad JB, Bacha F, Braffett BH, Arslanian S, Urbina EM. Longitudinal changes in vascular stiffness and heart rate variability among young adults with youth-onset type 2 diabetes: results from the follow-up observational treatment options for type 2 diabetes in adolescents and youth (TODAY) study. Acta Diabetol. 2022 Feb;59(2):197-205. doi: 10.1007/s00592-021-01796-6. Epub 2021 Sep 20.

  PMID: 34542729 DERIVED

• TODAY Study Group. Health Care Coverage and Glycemic Control in Young Adults With Youth-Onset Type 2 Diabetes: Results From the TODAY2 Study. Diabetes Care. 2020 Oct;43(10):2469-2477. doi: 10.2337/dc20-0760. Epub 2020 Aug 10.

  PMID: 32778555 DERIVED

• TODAY Study Group. Longitudinal Changes in Cardiac Structure and Function From Adolescence to Young Adulthood in Participants With Type 2 Diabetes Mellitus: The TODAY Follow-Up Study. Circ Heart Fail. 2020 Jun;13(6):e006685. doi: 10.1161/CIRCHEARTFAILURE.119.006685. Epub 2020 Jun 5.

  PMID: 32498621 DERIVED

• Saletsky RD, Trief PM, Anderson BJ, Rosenbaum P, Weinstock RS. Parenting style, parent-youth conflict, and medication adherence in youth with type 2 diabetes participating in an intensive lifestyle change intervention. Fam Syst Health. 2014 Jun;32(2):176-85. doi: 10.1037/fsh0000008. Epub 2014 Feb 17.

  PMID: 24548045 DERIVED

Related Links

• public access to intervention materials used in TODAY

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin; Rosiglitazone

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Thiazolidinediones; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Kathryn Hirst, Coordinating Center PI
• Organization: TODAY Coordinating Center at George Washington University Biostatistics Center

khirst@bsc.gwu.edu

301-881-9260

Study Officials

• Phil Zeitler, MD, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

• Kathryn Hirst, PhD

  George Washington University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2004
• First Posted: April 12, 2004
• Study Start: May 1, 2004
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2014
• Last Updated: July 30, 2021
• Results First Posted: December 16, 2014

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share

Locations

US (16)