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CompletedNCT00081328TODAYUpdated Jul 30, 2021Results posted

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

A Phase 3 interventional study of Metformin and Rosiglitazone in Diabetes Mellitus, Type II, sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Completed at 16 sites in United States. Open to participants aged 10 Years to 17 Years. Per ClinicalTrials.gov, last updated 2021-07-30.

Sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
699
Allocation
Randomized
Ages
10 Years to 17 Years
Sex
All
01

Study 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.

Read the detailed description

T2DM has dramatically increased throughout the world in many ethnic groups and among people with diverse social and economic backgrounds. Over the last decade, the increase in the number of children and youth with T2DM has been labeled an "epidemic". Before the 1990s, it was rare for most pediatric centers to have patients with T2DM. By 1994, T2DM patients represented up to 16% of new cases of diabetes in children in urban areas, and by 1999, depending on geographic location, the range of percent of new cases due to T2DM was between 8-45% and disproportionately represented in minority populations.

T2DM in children and youth, as in adults, is due to the combination of insulin resistance and relative β-cell failure. It appears that there are a host of genetic and environmental risk factors for insulin resistance and limited β-cell reserve. The epidemic of pediatric T2DM is coincident with the rise in the number of children who are overweight or at risk for overweight and with a decrease in the physical activity pattern of youth. There has been a strong association between T2DM and the onset of puberty, a positive family history of T2DM, and elements of the metabolic syndrome such as acanthosis nigricans and polycystic ovarian syndrome (PCOS).

Preceding the development of frank diabetes, children and youth experience a period of prediabetes. Prediabetes is defined as either elevated fasting glucose or impaired glucose tolerance. Despite the dramatic increase in the number of cases of prediabetes and T2DM in pediatric populations, there have been no published large-scale studies investigating the pathophysiology, treatment, and complications of these disorders in children and youth. The long-term complications and costs associated with T2DM make such studies imperative. Between 1997 and 2002, the estimated cost of diabetes with regard to direct medical cost increased from $44 billion to $92 billion, and the total cost increased from $98 billion to $132 billion. The vast majority of monies are spent on the long-term complications of this disorder. Since the long-term microvascular and cardiovascular complications relate to duration of diabetes and to control of glycemia, it could be hypothesized that the increasing number of children and youth diagnosed with T2DM, if not effectively treated, could dramatically add to the economic burden of this disease over the ensuing decades.

Except in American Indian youth, there are no population-based data available with regard to prevalence of T2DM. Instead, only clinic-based reports indicate that there has been a tremendous increase in the number of children and adolescents with T2DM. T2DM occurs almost exclusively in children and youth who are overweight or at risk for overweight (BMI > 85th percentile for age). At the time of diagnosis, most pediatric patients are in the midst of Tanner Stage 2-4 puberty. Puberty contributes to insulin resistance due to augmentation of growth hormone secretion, and if these normal pubertal physiologic changes are not compensated for by increased insulin secretion, frank diabetes will develop. Half to three-quarters of patients have a parent and close to ninety percent have at least one first or second degree relative with T2DM. The clinical presentation of T2DM in youth ranges from mild asymptomatic hyperglycemia to severe ketoacidosis. In those who present with clinical symptoms due to hyperglycemia, glycosuria and weight loss are present in 20-40%, ketonuria is present in 33% and ketoacidosis is found in 5-10%. Patients without clinical symptoms are diagnosed as the result of routine blood or urine testing during a health care visit or by investigating a variety of complaints such as chronic infection, sleep apnea, hyperlipidemia, hypertension, and hirsutism or irregular periods associated with PCOS. It may be difficult to distinguish T1DM from T2DM at presentation. The absence of autoantibodies is a prerequisite for the diagnosis of T2DM. In addition, evidence of residual insulin secretion is suggestive of T2DM rather than T1DM.

Patients with T2DM have dual abnormalities of insulin resistance and insulin deficiency. It is hypothesized that to achieve the level of glycemic control required to optimize long-term outcome and decrease or prevent microvascular complications, treatment regimens should theoretically be designed to improve insulin resistance and preserve residual β-cell function. The available anti-diabetic agents have not been adequately evaluated in pediatric patients. This is particularly relevant with regard to using combination therapy to improve glycemic control or lifestyle interventions aimed at obesity and sedentary behavior.

02

Conditions studied

  • Diabetes Mellitus, Type II
03

In context

Diabetes Mellitus

10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.

This study's enrollment of 699 is above the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.

Browse Diabetes Mellitus studies →

Lead sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is the lead sponsor of 529 studies on the registry; 54 are open to participants now.

Of its 79 completed or terminated interventional studies of FDA-regulated products, 50 (63%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
10 Years to 17 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria (during Screening and Run-in period):

  • 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.

Exclusion Criteria (during Screening and Run-in period):

  • 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.
  • Abnormal reticulocyte count or HbA1c chromatogram at time of screening.
  • Admitted use of anabolic steroids within the past 60 days.
  • Other significant organ system illness or condition (including psychiatric or developmental disorder) that would prevent participation in the opinion of the investigator.
  • Patient participates in a formal weight-loss program.

Inclusion Criteria (post Run-in and Randomization):

  • Duration since diagnosis less than 2 years at randomization.
  • HbA1c \< 8% on metformin alone.
  • Age 10-17, with randomization before patient is 18 years old.
  • Signed consent/assent forms for randomization and the post-randomization phase.
  • 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.

Exclusion Criteria (post Run-in and Randomization):

  • Refractory hypertension: average systolic blood pressure ≥ 150 mmHg or average diastolic blood pressure ≥ 95 mmHg despite appropriate medical therapy.
  • Refractory hyperlipidemia: total cholesterol > 300 mg/dL or LDL > 190 mg/dL or triglycerides > 800 mg/dL, despite appropriate medical therapy.
  • Refractory anemia: hematocrit \< 30% or hemoglobin \< 10 gm/dL despite appropriate medical therapy.
  • Patient on a thiazolidinedione (TZD) within the last 12 weeks.
  • Patient on non-study diabetes medications within the past 6 weeks.
  • 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, assessed by mastery of standard diabetes education program administered during run-in.
  • Inability to comply with requirements of study during run-in period.
  • 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.
  • Physical limitations preventing patient from being randomized to the lifestyle intervention.
  • Patient plans to leave the geographic area within one calendar year.
  • Admitted use of anabolic steroids within 60 days.
  • Other significant organ system illness or condition (including psychiatric or developmental disorder) that would prevent participation in the opinion of the investigator.
  • Patient participates in a formal weight loss program.
  • Episode of DKA during the run-in.30.
  • Edema at the time of randomization (a participant who experiences edema during run-in must have recovered within 2 weeks and be edema free for 1 week prior to randomization).
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
699 participants (actual)

Study arms

  • Experimental
    1

    Metformin alone

    Drug: Metformin

  • Experimental
    2

    Metformin + Rosiglitazone

    Drug: Metformin · Drug: Rosiglitazone

  • Experimental
    3

    Metformin + Lifestyle Program

    Drug: Metformin · Behavioral: Lifestyle Program

Interventions

  • DrugMetformin

    capsule, 1000 mg bid

  • DrugRosiglitazone

    capsule, 4 mg bid

  • BehavioralLifestyle Program

    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

06

What researchers measure

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)

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

Secondary outcomes

  1. Insulin Sensitivity

    All participants were followed to 24 months. Insulin sensitivity is measured from OGTT as inverse of fasting insulin (mL/uU). The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time.

    Time frame: 24 months

  2. Number of Serious Adverse Events

    Number of serious adverse events reported during the trial. Participant could have multiple episodes reported.

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

  3. Insulin Secretion

    Insulinogenic index determined from OGTT as difference in insulin at 30 minutes minus 0 minutes divided by difference in glucose at 30 minutes minus 0 minutes. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time.

    Time frame: 24 months

  4. Body Composition -- BMI

    Body mass index (BMI) measured in kg per meters squared. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time.

    Time frame: 24 months

  5. Body Composition -- Waist Circumference

    Waist circumference (cm) measured at the iliac crest at its outermost point with the measuring tape placed around the participant in a horizontal plane parallel to the floor at the mark and the measurement teken at the end of normal expiration without the tape compressing the skin. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time.

    Time frame: 24 months

  6. Body Composition -- Bone Density

    Measured by DXA, both whole body scan and AP-spine scan. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. In addition, in about 1/3 of participants DXA scans could not be obtained on participants weighing more than 300 pounds (136 kg), the upper limit in size set by the machine manufacturers. Scans were considered invalid if a body part (e.g., arm, leg) was completely off or partially off the scanner, there was hand-hip overlap, or there was motion or movement during the scan.

    Time frame: 24 months

  7. Body Composition -- Fat Mass

    Determined by DXA whole body scan. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. In addition, in about 1/3 of participants DXA scans could not be obtained on participants weighing more than 300 pounds (136 kg), the upper limit in size set by the machine manufacturers. Scans were considered invalid if a body part (e.g., arm, leg) was completely off or partially off the scanner, there was hand-hip overlap, or there was motion or movement during the scan.

    Time frame: 24 months

  8. Comorbidity -- Hypertension

    A diagnosis was made by an out-of-range value \>=95th percentile or systolic \>=130 or diastolic \>=80 sustained over 6 months or on an anti-hypertensive medication.

    Time frame: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.

  9. Comorbidity -- LDL Dyslipidemia

    A diagnosis was made from out-of-range value \>= 130 mg/dL sustained over 6 months or put on lipid lowering medication.

    Time frame: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.

  10. Comorbidity -- Triglycerides Dyslipidemia

    A diagnosis was made by an out-of-range value \>=150 mg/dL sustained over 6 months or on appropriate lipid lowering medication.

    Time frame: Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.

07

Results

Posted Dec 16, 2014

Participant flow

Participants were recruited from July 2004 to February 2009. Participants were recruited from the patient populations of pediatric endocrine clinics at the participating study clinical centers, including satellite clinics. Posters announced the study. Study staff approached youth and their families during medical visits.

Participant flow — Overall Study
Milestone1 Metformin Alone2 Metformin + Rosliglitazone3 Metformin + Lifestyle Program
Started232233234
Completed232233234
Not completed000

Outcome measures

PrimaryTreatment 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)

Time frame:
Study duration - 2 years to 6.5 years of follow up from randomization
Reported as:
Number · participants
Treatment Failure (Loss of Glycemic Control)
participants1 Metformin Alone2 Metformin + Rosliglitazone3 Metformin + Lifestyle Program
Treatment failure12090109
Did not fail treatment during trial112143125
SecondaryInsulin Sensitivity

All participants were followed to 24 months. Insulin sensitivity is measured from OGTT as inverse of fasting insulin (mL/uU). The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time.

Time frame:
24 months
Reported as:
Median · mL/uU
Insulin Sensitivity
mL/uU1 Metformin Alone2 Metformin + Rosiglitazone3 Metformin + Lifestyle Program
Insulin Sensitivity0.037 (0.023 to 0.061)0.049 (0.031 to 0.068)0.039 (0.027 to 0.064)
SecondaryNumber of Serious Adverse Events

Number of serious adverse events reported during the trial. Participant could have multiple episodes reported.

Time frame:
Reported as occurred during study follow-up - 2 years to 6.5 years from randomization.
Reported as:
Number · episodes of serious adverse event
Number of Serious Adverse Events
episodes of serious adverse event1 Metformin Alone2 Metformin + Rosiglitazone3 Metformin + Lifestyle Program
Number of Serious Adverse Events423458
SecondaryInsulin Secretion

Insulinogenic index determined from OGTT as difference in insulin at 30 minutes minus 0 minutes divided by difference in glucose at 30 minutes minus 0 minutes. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time.

Time frame:
24 months
Reported as:
Median · uU/mL divided by mg/dL
Insulin Secretion
uU/mL divided by mg/dL1 Metformin Alone2 Metformin + Rosliglitazone3 Metformin + Lifestyle Program
Insulin Secretion.75 (.33 to 1.39).83 (.28 to 1.38).71 (.26 to 1.69)
SecondaryBody Composition -- BMI

Body mass index (BMI) measured in kg per meters squared. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time.

Time frame:
24 months
Reported as:
Mean · kg per meters squared
Body Composition -- BMI
kg per meters squared1 Metformin Alone2 Metformin + Rosliglitazone3 Metformin + Lifestyle Program
Body Composition -- BMI36.7 ± 9.138.2 ± 8.135.3 ± 8.4
SecondaryBody Composition -- Waist Circumference

Waist circumference (cm) measured at the iliac crest at its outermost point with the measuring tape placed around the participant in a horizontal plane parallel to the floor at the mark and the measurement teken at the end of normal expiration without the tape compressing the skin. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time.

Time frame:
24 months
Reported as:
Mean · cm
Body Composition -- Waist Circumference
cm1 Metformin Alone2 Metformin + Rosliglitazone3 Metformin + Lifestyle Program
Body Composition -- Waist Circumference110.8 ± 17.5114.0 ± 16.3108.6 ± 16.7
SecondaryBody Composition -- Bone Density

Measured by DXA, both whole body scan and AP-spine scan. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. In addition, in about 1/3 of participants DXA scans could not be obtained on participants weighing more than 300 pounds (136 kg), the upper limit in size set by the machine manufacturers. Scans were considered invalid if a body part (e.g., arm, leg) was completely off or partially off the scanner, there was hand-hip overlap, or there was motion or movement during the scan.

Time frame:
24 months
Reported as:
Mean · g/cm squared
Body Composition -- Bone Density
g/cm squared1 Metformin Alone2 Metformin + Rosliglitazone3 Metformin + Lifestyle Program
Body Composition -- Bone Density1.15 ± .101.15 ± .111.15 ± .12
SecondaryBody Composition -- Fat Mass

Determined by DXA whole body scan. The analysis sample includes only participants with 24 month data who had not experienced the primary outcome by that time. In addition, in about 1/3 of participants DXA scans could not be obtained on participants weighing more than 300 pounds (136 kg), the upper limit in size set by the machine manufacturers. Scans were considered invalid if a body part (e.g., arm, leg) was completely off or partially off the scanner, there was hand-hip overlap, or there was motion or movement during the scan.

Time frame:
24 months
Reported as:
Mean · kg
Body Composition -- Fat Mass
kg1 Metformin Alone2 Metformin + Rosliglitazone3 Metformin + Lifestyle Program
Body Composition -- Fat Mass36.1 ± 12.039.7 ± 10.532.2 ± 9.4
SecondaryComorbidity -- Hypertension

A diagnosis was made by an out-of-range value \>=95th percentile or systolic \>=130 or diastolic \>=80 sustained over 6 months or on an anti-hypertensive medication.

Time frame:
Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.
Reported as:
Number · participants
Comorbidity -- Hypertension
participants1 Metformin Alone2 Metformin + Rosliglitazone3 Metformin + Lifestyle Program
Comorbidity -- Hypertension575345
SecondaryComorbidity -- LDL Dyslipidemia

A diagnosis was made from out-of-range value \>= 130 mg/dL sustained over 6 months or put on lipid lowering medication.

Time frame:
Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.
Reported as:
Number · participants
Comorbidity -- LDL Dyslipidemia
participants1 Metformin Alone2 Metformin + Rosliglitazone3 Metformin + Lifestyle Program
Comorbidity -- LDL Dyslipidemia181615
SecondaryComorbidity -- Triglycerides Dyslipidemia

A diagnosis was made by an out-of-range value \>=150 mg/dL sustained over 6 months or on appropriate lipid lowering medication.

Time frame:
Data collected at baseline and during follow-up - 2 years to 6.5 years from randomization.
Reported as:
Number · participants
Comorbidity -- Triglycerides Dyslipidemia
participants1 Metformin Alone2 Metformin + Rosliglitazone3 Metformin + Lifestyle Program
Comorbidity -- Triglycerides Dyslipidemia202822

Adverse events

Collected over During the 2-6 month pre-randomization run-in period and during follow-up from 2-6.5 years.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
1 Metformin Alone—42/232 (18.1%)215/232 (92.7%)
2 Metformin + Rosliglitazone—34/233 (14.6%)196/233 (84.1%)
3 Metformin + Lifestyle Program—58/234 (24.8%)213/234 (91%)
Most frequent serious events
Most frequent serious events
Event1 Metformin Alone2 Metformin + Rosliglitazone3 Metformin + Lifestyle Program
all otherGeneral disorders32/23225/23351/234
Diabetic ketoacidosisEndocrine disorders5/2323/2333/234
HyperglycemiaEndocrine disorders3/2325/2332/234
HypoglycemiaEndocrine disorders1/2321/2332/234
Lactic acidosisEndocrine disorders1/2320/2330/234
Most frequent other events
Most frequent other events
Event1 Metformin Alone2 Metformin + Rosliglitazone3 Metformin + Lifestyle Program
Infection requiring medical attentionInfections and infestations149/232120/233151/234
Gastrointestinal symptomsGastrointestinal disorders129/232100/233136/234
Hyperglycemia symptomsEndocrine disorders115/23298/233103/234
Skin rash on physical examinationSkin and subcutaneous tissue disorders108/232101/23395/234
Muscle ache or painMusculoskeletal and connective tissue disorders68/23253/23377/234
Sprain or fracture requiring medical attentionMusculoskeletal and connective tissue disorders66/23253/23364/234
Mild hypoglycemiaEndocrine disorders10/23219/2338/234
Edema on physical examinationSkin and subcutaneous tissue disorders17/23217/23317/234

Baseline characteristics

Age 10-17 years with T2D according to American Diabetes Association criteria for less than 2 years, body mass index (BMI) \>=85th percentile, negative diabetes autoantibodies, fasting c-peptide \>0.6 ng/mL, and an adult caregiver willing to actively support study participation.

Age, Continuous
Age, Continuous(years)1 Metformin Alone2 Metformin + Rosiglitazone3 Metformin + Lifestyle ProgramTotal
Mean14.1 ± 1.914.1 ± 2.113.8 ± 2.014.0 ± 2.0
Sex: Female, Male
Sex: Female, Male(Participants)1 Metformin Alone2 Metformin + Rosiglitazone3 Metformin + Lifestyle ProgramTotal
Female146152154452
Male868180247
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)1 Metformin Alone2 Metformin + Rosiglitazone3 Metformin + Lifestyle ProgramTotal
American Indian12161341
Black Non-Hispanic776486227
Hispanic9110186278
White Non-Hispanic494746142
Asian Non-Hispanic35311
Region of Enrollment
Region of Enrollment(participants)1 Metformin Alone2 Metformin + Rosiglitazone3 Metformin + Lifestyle ProgramTotal
United States232233234699
Body mass index z-score
Body mass index z-score(z-score)1 Metformin Alone2 Metformin + Rosiglitazone3 Metformin + Lifestyle ProgramTotal
Mean2.27 ± 0.452.22 ± 0.492.18 ± 0.462.23 ± 0.47
Percent overweight
Percent overweight(100% X (BMI-50th %ile)/50th %ile)1 Metformin Alone2 Metformin + Rosiglitazone3 Metformin + Lifestyle ProgramTotal
Mean82.1 ± 38.379.1 ± 38.175.6 ± 35.378.9 ± 37.3
Duration of diabetes
Duration of diabetes(months)1 Metformin Alone2 Metformin + Rosiglitazone3 Metformin + Lifestyle ProgramTotal
Mean7.8 ± 6.08.0 ± 5.77.6 ± 5.87.8 ± 5.8
Total annual household income
Total annual household income(participants)1 Metformin Alone2 Metformin + Rosiglitazone3 Metformin + Lifestyle ProgramTotal
< $25,000818692259
$25,000-49,999836166210
>=$50,000445853155
unknown24282375

10 further baseline measures are reported on the registry.

08

Study locations

16 sites
  • Children's Hospital Los Angeles
    Los Angeles, California 90027, United States
  • University of Colorado Health Sciences Center, The Children's Hospital
    Denver, Colorado 80262, United States
  • Yale University
    New Haven, Connecticut 06520, United States
  • George Washington University Biostatistics Center
    Rockville, Maryland 20852, United States
  • Massachusetts General Hospital Diabetes Center
    Boston, Massachusetts 02114, United States
  • Joslin Diabetes Center
    Boston, Massachusetts 02215, United States
  • Saint Louis University Health Sciences Center
    Saint Louis, Missouri 63104, United States
  • Washington University Department of Pediatrics
    Saint Louis, Missouri 63110, United States
  • Columbia University Medical Center
    New York, New York 10032, United States
  • State University of New York Upstate Medical University
    Syracuse, New York 13210, United States
  • Case Western Reserve
    Cleveland, Ohio 44106, United States
  • University of Oklahoma
    Oklahoma City, Oklahoma 93104, United States
  • Children's Hospital of Philadelphia
    Philadelphia, Pennsylvania 19104, United States
  • Children's Hospital of Pittsburgh
    Pittsburgh, Pennsylvania 15213, United States
  • Baylor College of Medicine
    Houston, Texas 77030, United States
  • University of Texas Health Science Center at San Antonio
    San Antonio, Texas 78229, United States
09

References and documents

Publications

  • 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. PubMed 17448130 ↗
  • 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. PubMed 19774104 ↗
  • 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. PubMed 19244566 ↗
  • 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. PubMed 19823189 ↗
  • 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. PubMed 24955003 ↗
  • 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. PubMed 25389367 ↗
  • 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. PubMed 28486851 ↗
  • 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. PubMed 31081852 ↗
  • 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. PubMed 31119838 ↗
  • 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. PubMed 20519658 ↗
  • 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. PubMed 20962021 ↗
  • 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. PubMed 21357794 ↗
  • 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. PubMed 21836107 ↗
  • 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. PubMed 22369102 ↗
  • 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. PubMed 22332798 ↗
  • 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. PubMed 22540912 ↗
  • 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. PubMed 23400602 ↗
  • 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. PubMed 23438494 ↗
  • 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. Erratum In: Diabetes Care. 2013 Aug;36(8):2448. PubMed 23704672 ↗
  • 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. PubMed 23704673 ↗
  • 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. PubMed 23704674 ↗
  • 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. PubMed 23704675 ↗
  • 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. PubMed 23704676 ↗
  • 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. PubMed 23704677 ↗
  • 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. PubMed 24450390 ↗
  • 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. PubMed 24702733 ↗
  • 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. PubMed 24948348 ↗
  • 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. PubMed 25468310 ↗
  • 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. PubMed 25784663 ↗
  • 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. PubMed 26047470 ↗
  • 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. PubMed 25702853 ↗
  • 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. PubMed 27057209 ↗
  • 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. PubMed 26537182 ↗
  • 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. PubMed 26531295 ↗
  • 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. PubMed 26577415 ↗
  • 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. PubMed 26628417 ↗
  • 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. PubMed 25690268 ↗
  • 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. PubMed 26859798 ↗
  • 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. PubMed 27803118 ↗
  • 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. PubMed 27161901 ↗
  • 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. PubMed 27426901 ↗
  • 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. PubMed 27352955 ↗
  • 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. PubMed 27499218 ↗
  • 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. PubMed 28378429 ↗
  • 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. PubMed 28664624 ↗
  • 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. Erratum In: Am J Kidney Dis. 2019 Apr;73(4):580. doi: 10.1053/j.ajkd.2019.02.001. PubMed 29157731 ↗
  • 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. PubMed 29246363 ↗
  • 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. PubMed 29758564 ↗
  • 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. PubMed 29146120 ↗
  • 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. PubMed 29398050 ↗
  • 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. PubMed 29532078 ↗
  • 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. PubMed 29427697 ↗
  • 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. PubMed 29697830 ↗
  • 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. PubMed 29936086 ↗
  • 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. PubMed 30455329 ↗
  • 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. PubMed 30833375 ↗
  • 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. PubMed 30967435 ↗
  • 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. PubMed 31167889 ↗
  • 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. PubMed 31418516 ↗
  • 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. PubMed 31501226 ↗
  • 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. PubMed 31685489 ↗
  • 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. PubMed 31809265 ↗
  • 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. PubMed 31886931 ↗
  • 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. PubMed 32064729 ↗
  • 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. PubMed 32501612 ↗
  • 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. PubMed 33071178 ↗
  • 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. PubMed 36150365 ↗
  • 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. PubMed 35149207 ↗
  • 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. PubMed 35123868 ↗
  • 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. PubMed 35015056 ↗
  • 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. PubMed 34542729 ↗
  • 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. PubMed 32778555 ↗
  • 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. PubMed 32498621 ↗
  • 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. PubMed 24548045 ↗

Individual participant data

Plan to share: Yes — Data are available at the NIDDK Central Repository

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 30, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00081328
Lead sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Responsible party
Sponsor
First posted
Apr 12, 2004
Start date
May 2004
Primary completion
Feb 2011
Completion
Feb 2014
Results posted
Dec 16, 2014
Last update
Jul 30, 2021

Study contacts

Phil Zeitler, MD, PhD
principal investigator · University of Colorado, Denver
Kathryn Hirst, PhD
principal investigator · George Washington University

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jul 2021. You cannot join it, but the record below documents what was studied.

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