Safety and tolerability of the treatment of youth-onset type 2 diabetes

The TODAY experience

Neil H. White, Laura Pyle, Steven M. Willi, Trang Pham, Steven D. Chernausek, Robin Goland, Daniel Hale, Morey W. Haymond, Kristen J. Nadeau, Sumana Narasimhan

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

OBJECTIVE - Data related to the safety and tolerability of treatments for pediatric type 2 diabetes are limited. The TODAY clinical trial assessed severe adverse events (SAEs) and targeted nonsevere adverse events (AEs) before and after treatment failure, which was the primary outcome (PO). RESEARCH DESIGN AND METHODS - Obese 10- to 17-year-olds ( N = 699) with type 2 diabetes for <2 years and hemoglobin A1c (A1C) ≤8% on metformin monotherapy were randomized to one of three treatments: metformin, metformin plus rosiglitazone (M + R), or metformin plus lifestyle program (M + L). Participants were followed for 2 -6.5 years. RESULTS - Gastrointestinal (GI) disturbance was the most common AE (41%) and was lower in the M+ R group (P = 0.018). Other common AEs included anemia (20%before PO, 14%after PO), abnormal liver transaminases (16, 15%), excessive weight gain (7, 9%), and psychological events (10, 18%); the AEs were similar across treatments. Permanent medication reductions/discontinuations occurred most often because of abnormal liver transaminases and were lowest in the M + R group (P = 0.005). Treatment-emergent SAEs were uncommon and similar across treatments. Most (98%) were unrelated or unlikely related to the study intervention. There were no deaths and only 18 targeted SAEs (diabetic ketoacidosis, n = 12; severe hypoglycemia, n = 5; lactic acidosis, n = 1). There were 62 pregnancies occurring in 45 participants, and 6 infants had congenital anomalies. CONCLUSIONS - The TODAY study represents extensive experience managing type 2 diabetes in youth and found that the three treatment approaches were generally safe and well tolerated. Adding rosiglitazone to metformin may reduce GI side effects and hepatotoxicity.

Original languageEnglish (US)
Pages (from-to)1765-1771
Number of pages7
JournalDiabetes care
Volume36
Issue number6
DOIs
StatePublished - Jun 1 2013

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Metformin
Type 2 Diabetes Mellitus
rosiglitazone
Safety
Transaminases
Therapeutics
Diabetic Ketoacidosis
Lactic Acidosis
Liver
Treatment Failure
Hypoglycemia
Weight Gain
Life Style
Anemia
Hemoglobins
Research Design
Clinical Trials
Pediatrics
Psychology
Pregnancy

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

White, N. H., Pyle, L., Willi, S. M., Pham, T., Chernausek, S. D., Goland, R., ... Narasimhan, S. (2013). Safety and tolerability of the treatment of youth-onset type 2 diabetes: The TODAY experience. Diabetes care, 36(6), 1765-1771. https://doi.org/10.2337/dc12-2390
White, Neil H. ; Pyle, Laura ; Willi, Steven M. ; Pham, Trang ; Chernausek, Steven D. ; Goland, Robin ; Hale, Daniel ; Haymond, Morey W. ; Nadeau, Kristen J. ; Narasimhan, Sumana. / Safety and tolerability of the treatment of youth-onset type 2 diabetes : The TODAY experience. In: Diabetes care. 2013 ; Vol. 36, No. 6. pp. 1765-1771.
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White, NH, Pyle, L, Willi, SM, Pham, T, Chernausek, SD, Goland, R, Hale, D, Haymond, MW, Nadeau, KJ & Narasimhan, S 2013, 'Safety and tolerability of the treatment of youth-onset type 2 diabetes: The TODAY experience', Diabetes care, vol. 36, no. 6, pp. 1765-1771. https://doi.org/10.2337/dc12-2390

Safety and tolerability of the treatment of youth-onset type 2 diabetes : The TODAY experience. / White, Neil H.; Pyle, Laura; Willi, Steven M.; Pham, Trang; Chernausek, Steven D.; Goland, Robin; Hale, Daniel; Haymond, Morey W.; Nadeau, Kristen J.; Narasimhan, Sumana.

In: Diabetes care, Vol. 36, No. 6, 01.06.2013, p. 1765-1771.

Research output: Contribution to journalArticle

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T1 - Safety and tolerability of the treatment of youth-onset type 2 diabetes

T2 - The TODAY experience

AU - White, Neil H.

AU - Pyle, Laura

AU - Willi, Steven M.

AU - Pham, Trang

AU - Chernausek, Steven D.

AU - Goland, Robin

AU - Hale, Daniel

AU - Haymond, Morey W.

AU - Nadeau, Kristen J.

AU - Narasimhan, Sumana

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Y1 - 2013/6/1

N2 - OBJECTIVE - Data related to the safety and tolerability of treatments for pediatric type 2 diabetes are limited. The TODAY clinical trial assessed severe adverse events (SAEs) and targeted nonsevere adverse events (AEs) before and after treatment failure, which was the primary outcome (PO). RESEARCH DESIGN AND METHODS - Obese 10- to 17-year-olds ( N = 699) with type 2 diabetes for <2 years and hemoglobin A1c (A1C) ≤8% on metformin monotherapy were randomized to one of three treatments: metformin, metformin plus rosiglitazone (M + R), or metformin plus lifestyle program (M + L). Participants were followed for 2 -6.5 years. RESULTS - Gastrointestinal (GI) disturbance was the most common AE (41%) and was lower in the M+ R group (P = 0.018). Other common AEs included anemia (20%before PO, 14%after PO), abnormal liver transaminases (16, 15%), excessive weight gain (7, 9%), and psychological events (10, 18%); the AEs were similar across treatments. Permanent medication reductions/discontinuations occurred most often because of abnormal liver transaminases and were lowest in the M + R group (P = 0.005). Treatment-emergent SAEs were uncommon and similar across treatments. Most (98%) were unrelated or unlikely related to the study intervention. There were no deaths and only 18 targeted SAEs (diabetic ketoacidosis, n = 12; severe hypoglycemia, n = 5; lactic acidosis, n = 1). There were 62 pregnancies occurring in 45 participants, and 6 infants had congenital anomalies. CONCLUSIONS - The TODAY study represents extensive experience managing type 2 diabetes in youth and found that the three treatment approaches were generally safe and well tolerated. Adding rosiglitazone to metformin may reduce GI side effects and hepatotoxicity.

AB - OBJECTIVE - Data related to the safety and tolerability of treatments for pediatric type 2 diabetes are limited. The TODAY clinical trial assessed severe adverse events (SAEs) and targeted nonsevere adverse events (AEs) before and after treatment failure, which was the primary outcome (PO). RESEARCH DESIGN AND METHODS - Obese 10- to 17-year-olds ( N = 699) with type 2 diabetes for <2 years and hemoglobin A1c (A1C) ≤8% on metformin monotherapy were randomized to one of three treatments: metformin, metformin plus rosiglitazone (M + R), or metformin plus lifestyle program (M + L). Participants were followed for 2 -6.5 years. RESULTS - Gastrointestinal (GI) disturbance was the most common AE (41%) and was lower in the M+ R group (P = 0.018). Other common AEs included anemia (20%before PO, 14%after PO), abnormal liver transaminases (16, 15%), excessive weight gain (7, 9%), and psychological events (10, 18%); the AEs were similar across treatments. Permanent medication reductions/discontinuations occurred most often because of abnormal liver transaminases and were lowest in the M + R group (P = 0.005). Treatment-emergent SAEs were uncommon and similar across treatments. Most (98%) were unrelated or unlikely related to the study intervention. There were no deaths and only 18 targeted SAEs (diabetic ketoacidosis, n = 12; severe hypoglycemia, n = 5; lactic acidosis, n = 1). There were 62 pregnancies occurring in 45 participants, and 6 infants had congenital anomalies. CONCLUSIONS - The TODAY study represents extensive experience managing type 2 diabetes in youth and found that the three treatment approaches were generally safe and well tolerated. Adding rosiglitazone to metformin may reduce GI side effects and hepatotoxicity.

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White NH, Pyle L, Willi SM, Pham T, Chernausek SD, Goland R et al. Safety and tolerability of the treatment of youth-onset type 2 diabetes: The TODAY experience. Diabetes care. 2013 Jun 1;36(6):1765-1771. https://doi.org/10.2337/dc12-2390