Safety and tolerability of the treatment of youth-onset type 2 diabetes: The TODAY experience

Document Type

Journal Article

Publication Date



Diabetes Care


Volume 36, Issue 6

Inclusive Pages



Diabetes Mellitus, Type 2--drug therapy; Hypoglycemic Agents--adverse effects


OBJECTIVE Data related to the safety and tolerability of treatments for pediatrictype 2 diabetes are limited. The TODAY clinical trial assessed severe adverse events (SAEs) and targeted nonsevere adverse events (AEs) before and after treatmentfailure, which was the primary outcome (PO).

RESEARCH DESIGN AND METHODS Obese 10- to 17-year-olds (N = 699) withtype 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 ofabnormal 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 deathsand 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 2diabetes in youth and found that the three treatment approaches were generally safeand well tolerated. Adding rosiglitazone to metformin may reduce GI side effects andhepatotoxicity.


Reproduced with permission of the American Diabetes Association. Diabetes Care.

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