PMID- 23704676
OWN - NLM
STAT- MEDLINE
DCOM- 20131226
LR  - 20221207
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Print)
IS  - 0149-5992 (Linking)
VI  - 36
IP  - 6
DP  - 2013 Jun
TI  - Safety and tolerability of the treatment of youth-onset type 2 diabetes: the 
      TODAY experience.
PG  - 1765-71
LID - 10.2337/dc12-2390 [doi]
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.
CN  - TODAY Study Group
LA  - eng
SI  - ClinicalTrials.gov/NCT00081328
GR  - UL1 TR000005/TR/NCATS NIH HHS/United States
GR  - UL1-RR024153/RR/NCRR NIH HHS/United States
GR  - U01-DK61239/DK/NIDDK NIH HHS/United States
GR  - UL1 RR025780/RR/NCRR NIH HHS/United States
GR  - U01 DK061212/DK/NIDDK NIH HHS/United States
GR  - M01 RR014467/RR/NCRR NIH HHS/United States
GR  - UL1 RR025758/RR/NCRR NIH HHS/United States
GR  - M01 RR000084/RR/NCRR NIH HHS/United States
GR  - M01-RR00043-45/RR/NCRR NIH HHS/United States
GR  - U01 DK061254/DK/NIDDK NIH HHS/United States
GR  - UL1 RR024139/RR/NCRR NIH HHS/United States
GR  - UL1 RR024989/RR/NCRR NIH HHS/United States
GR  - P30 DK092950/DK/NIDDK NIH HHS/United States
GR  - UL1 RR024153/RR/NCRR NIH HHS/United States
GR  - M01-RR00125/RR/NCRR NIH HHS/United States
GR  - U01-DK61242/DK/NIDDK NIH HHS/United States
GR  - M01 RR000069/RR/NCRR NIH HHS/United States
GR  - U01-DK61254/DK/NIDDK NIH HHS/United States
GR  - U01-DK61212/DK/NIDDK NIH HHS/United States
GR  - UL1-RR025758/RR/NCRR NIH HHS/United States
GR  - UL1-RR024989/RR/NCRR NIH HHS/United States
GR  - U01 DK061242/DK/NIDDK NIH HHS/United States
GR  - U01-DK61230/DK/NIDDK NIH HHS/United States
GR  - UL1 RR024992/RR/NCRR NIH HHS/United States
GR  - M01-RR01066/RR/NCRR NIH HHS/United States
GR  - M01 RR001066/RR/NCRR NIH HHS/United States
GR  - U01 DK061230/DK/NIDDK NIH HHS/United States
GR  - UL1 TR000439/TR/NCATS NIH HHS/United States
GR  - UL1-RR024139/RR/NCRR NIH HHS/United States
GR  - UL1-RR025780/RR/NCRR NIH HHS/United States
GR  - UL1-RR024992/RR/NCRR NIH HHS/United States
GR  - UL1 TR000448/TR/NCATS NIH HHS/United States
GR  - M01 RR000043/RR/NCRR NIH HHS/United States
GR  - UL1-RR024134/RR/NCRR NIH HHS/United States
GR  - M01-RR00069/RR/NCRR NIH HHS/United States
GR  - M01-RR14467/RR/NCRR NIH HHS/United States
GR  - M01 RR000125/RR/NCRR NIH HHS/United States
GR  - U01 DK061239/DK/NIDDK NIH HHS/United States
GR  - UL1 RR024134/RR/NCRR NIH HHS/United States
GR  - M01-RR00084/RR/NCRR NIH HHS/United States
GR  - UL1 TR000130/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Blood Glucose)
RN  - 0 (Drug Combinations)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Thiazoles)
RN  - 0 (rosiglitazone-metformin combination)
RN  - 9100L32L2N (Metformin)
SB  - IM
CIN - Diabetes Care. 36:1732.
CIN - Diabetes Care. 36:1735.
CIN - Diabetes Care. 36:1742.
CIN - Diabetes Care. 36:1749.
CIN - Diabetes Care. 36:1758.
CIN - Diabetes Care. 36:1772.
CIN - Diabetes Care. 36:1775.
CIN - Diabetes Care. 36:1777.
MH  - Adolescent
MH  - Blood Glucose/drug effects
MH  - Child
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism
MH  - Drug Combinations
MH  - Female
MH  - Glycated Hemoglobin/metabolism
MH  - Humans
MH  - Hypoglycemic Agents/*adverse effects/therapeutic use
MH  - Male
MH  - Metformin/adverse effects/therapeutic use
MH  - Thiazoles/adverse effects/therapeutic use
PMC - PMC3661822
FIR - White, Neil H
IR  - White NH
FIR - Pyle, Laura
IR  - Pyle L
FIR - Willi, Steven M
IR  - Willi SM
FIR - Pham, Trang
IR  - Pham T
FIR - Chernausek, Steven D
IR  - Chernausek SD
FIR - Goland, Robin
IR  - Goland R
FIR - Berrie, Naomi
IR  - Berrie N
FIR - Hale, Daniel E
IR  - Hale DE
FIR - Haymond, Morey W
IR  - Haymond MW
FIR - Nadeau, Kristen J
IR  - Nadeau KJ
FIR - Narasimhan, Sumana
IR  - Narasimhan S
EDAT- 2013/05/25 06:00
MHDA- 2013/12/27 06:00
PMCR- 2014/06/01
CRDT- 2013/05/25 06:00
PHST- 2013/05/25 06:00 [entrez]
PHST- 2013/05/25 06:00 [pubmed]
PHST- 2013/12/27 06:00 [medline]
PHST- 2014/06/01 00:00 [pmc-release]
AID - dc12-2390 [pii]
AID - 2390 [pii]
AID - 10.2337/dc12-2390 [doi]
PST - ppublish
SO  - Diabetes Care. 2013 Jun;36(6):1765-71. doi: 10.2337/dc12-2390.