BACKGROUND: The prevalence of type 2 diabetes (T2D) in youth is increasing. Treatment options beyond metformin and insulin are needed. The safety, tolerability, pharmacokinetics, and pharmacodynamics of liraglutide once daily in youth (10-17 years old) with T2D were investigated in a randomized, double-blind, placebo-controlled trial. SUBJECTS AND METHODS: Youth treated with diet/exercise alone or with metformin and having a hemoglobin A1c (HbA1c) level of 6.5-11% were randomized to liraglutide (n=14) or placebo (n=7). Starting at 0.3 mg/day, doses were escalated weekly to 0.6, 0.9, 1.2, and 1.8 mg/day (or placebo equivalent) for 5 weeks. RESULTS: Nineteen participants completed the trial. Baseline characteristics were similar between groups, with mean (SD) values for age of 14.8 (2.2) years, weight of 113.2 (35.6) kg (range, 57-214 kg), diabetes duration of 1.7 (1.4) years, and HbA1c level of 8.1% (1.2%). No serious adverse events (AEs), including severe hypoglycemia, occurred. Transient gastrointestinal AEs were most common at lower liraglutide doses during dose escalation. No significant changes in safety and tolerability parameters occurred. There was no evidence of pancreatitis or lipase elevations above three times the upper normal limit; calcitonin levels remained within the normal range. For liraglutide 1.8 mg, mean half-life was 12 h, and clearance was 1.7 L/h. After 5 weeks, the decline in HbA1c level was greater with liraglutide versus placebo (-0.86 vs. 0.04%, P=0.0007), whereas mean body weight remained stable (-0.50 vs. -0.54 kg, P=0.9703). CONCLUSIONS: Liraglutide was well tolerated in youth with T2D, with safety, tolerability, and pharmacokinetic profiles similar to profiles in adults.
BACKGROUND: The prevalence of type 2 diabetes (T2D) in youth is increasing. Treatment options beyond metformin and insulin are needed. The safety, tolerability, pharmacokinetics, and pharmacodynamics of liraglutide once daily in youth (10-17 years old) with T2D were investigated in a randomized, double-blind, placebo-controlled trial. SUBJECTS AND METHODS: Youth treated with diet/exercise alone or with metformin and having a hemoglobin A1c (HbA1c) level of 6.5-11% were randomized to liraglutide (n=14) or placebo (n=7). Starting at 0.3 mg/day, doses were escalated weekly to 0.6, 0.9, 1.2, and 1.8 mg/day (or placebo equivalent) for 5 weeks. RESULTS: Nineteen participants completed the trial. Baseline characteristics were similar between groups, with mean (SD) values for age of 14.8 (2.2) years, weight of 113.2 (35.6) kg (range, 57-214 kg), diabetes duration of 1.7 (1.4) years, and HbA1c level of 8.1% (1.2%). No serious adverse events (AEs), including severe hypoglycemia, occurred. Transient gastrointestinal AEs were most common at lower liraglutide doses during dose escalation. No significant changes in safety and tolerability parameters occurred. There was no evidence of pancreatitis or lipase elevations above three times the upper normal limit; calcitonin levels remained within the normal range. For liraglutide 1.8 mg, mean half-life was 12 h, and clearance was 1.7 L/h. After 5 weeks, the decline in HbA1c level was greater with liraglutide versus placebo (-0.86 vs. 0.04%, P=0.0007), whereas mean body weight remained stable (-0.50 vs. -0.54 kg, P=0.9703). CONCLUSIONS: Liraglutide was well tolerated in youth with T2D, with safety, tolerability, and pharmacokinetic profiles similar to profiles in adults.
Authors: Phil Zeitler; Kathryn Hirst; Laura Pyle; Barbara Linder; Kenneth Copeland; Silva Arslanian; Leona Cuttler; David M Nathan; Sherida Tollefsen; Denise Wilfley; Francine Kaufman Journal: N Engl J Med Date: 2012-04-29 Impact factor: 91.245
Authors: Richard E Pratley; Michael Nauck; Timothy Bailey; Eduard Montanya; Robert Cuddihy; Sebastiano Filetti; Anne Bloch Thomsen; Rie Elvang Søndergaard; Melanie Davies Journal: Lancet Date: 2010-04-24 Impact factor: 79.321
Authors: Alan Garber; Robert Henry; Robert Ratner; Pedro A Garcia-Hernandez; Hiromi Rodriguez-Pattzi; Israel Olvera-Alvarez; Paula M Hale; Milan Zdravkovic; Bruce Bode Journal: Lancet Date: 2008-09-24 Impact factor: 79.321
Authors: John B Buse; Julio Rosenstock; Giorgio Sesti; Wolfgang E Schmidt; Eduard Montanya; Jason H Brett; Marcin Zychma; Lawrence Blonde Journal: Lancet Date: 2009-06-08 Impact factor: 79.321
Authors: Silvio E Inzucchi; Richard M Bergenstal; John B Buse; Michaela Diamant; Ele Ferrannini; Michael Nauck; Anne L Peters; Apostolos Tsapas; Richard Wender; David R Matthews Journal: Diabetes Care Date: 2012-04-19 Impact factor: 19.112
Authors: D Russell-Jones; A Vaag; O Schmitz; B K Sethi; N Lalic; S Antic; M Zdravkovic; G M Ravn; R Simó Journal: Diabetologia Date: 2009-08-14 Impact factor: 10.122
Authors: M Marre; J Shaw; M Brändle; W M W Bebakar; N A Kamaruddin; J Strand; M Zdravkovic; T D Le Thi; S Colagiuri Journal: Diabet Med Date: 2009-03 Impact factor: 4.359