Table 2.

Randomized Controlled Trials in Children/Adolescents Comparing Insulin Glargine with NPH Insulin, Ultralente and Continuous Subcutaneous Insulin Infusion

					Change from baseline		Frequency of hypoglycaemia (episodes/pt-month, % patients)
Reference	Design	No. Pts	Trial Duration	Treatments	A1C (%)	FBG (mmol/L)	Symptomatic	Nocturnal	Comments
Schober 200266 (Study 3001)	Multicenter, open-label, parallel group in children/adolescents aged 5–16 years	349	24 weeks	Bedtime Glargine NPH (od or bd)	+ 0.28% (baseline NR)  + 0.27% (baseline NR) P = 0.93	−1.29 mmol/L −0.68 mmol/L P = 0.02	Severe: 23% Severe: 29% P = 0.22	Severe 13% Severe: 18% P = 0.19	Once-daily glargine provides effective glycaemic control and is well tolerated in children and adolescents.
Murphy 200364	Open-label, cross-over study	28	32 weeks	Glargine (pre-bedtime) + lispro NPH (pre-bedtime) + RHI	−0.6% (baseline 9.3%) −0.2% (baseline 9.3%) P = 0.13	FBG 8.0 2-h post breakfast 8.1 Both P < 0.0005FBG 9.0, 2-h post breakfast 10.7	NR NR NR	32% nights 56% nights P < 0.05	Glargine + lispro reduced nocturnal hypoglycemia and was at least as effective as NPH + RHI in maintaining glycemic control in adolescents on multiple injection regimens.
Mianowska 200768	Prospective cross-over study in children aged 6–12 years	14	6 months	Glargine NPH	At 4 months: −0.6% (baseline 7.7%) At 4 months: 0.0% (baseline 7.7%) P = 0.007	−1.8 (baseline 9.8) −0.5 (baseline 9.8) P = 0.077	NR NR	No severe hypoglycaemia NR	Glargine provides better early morning and good glycaemic control, no increase in risk of severe hypoglycaemia.
Chase 200862 (Study 4030)	Open-label, multicenter parallel group	175	4 week run in period, 24 weeks	Glargine (od) + lispro (n = 85) NPH/lente (bd) (n = 90)	−0.25% ± 0.14% (baseline 7.8%) −0.05% ± 0.13% (baseline 8.0%) P = 0.1725a	Fasting SMBG: −3.3 mg/dL Fasting SMBG: + 1.1 mg/dL P = 0.6962	Severe: 0.20 events per patient year Severe: 0.09 events per patient year P = 0.1814	Confirmed BG < 70 mg/dLb<BR/>116 events per patient per year 94 events per patient per year P = 0.0298	Glargine is well tolerated for pediatric patients and may be more efficacious than NPH/lente in those with elevated A1C
Hassan 200867	Single center, parallel group study	42	3 months	Glargine (bd) + rapid acting insulin mixed in same syringe NPH (bd) + rapid acting insulin	−0.1% (baseline 6.8%)  + 0.7% (baseline 6.9%) P < 0.029	6.0 10.3 P < 0.008	0 events 7 events	NR NR	Glycemic control with glargine mixed with rapid-acting insulin analog bd was better than standard NPH therapy in newly diagnosed T1DM.

^aAnalysis of covariance, adjusting for baseline A1C, revealed a strong study arm effect on the slopes of the regression lines, indicating that the reduction in HbA1c was significantly greater with insulin glargine in those patients with higher baseline A1C values; ^bno differences in the occurrence of glucose levels <50 mg/dL (P = 0.82) or < 36 mg/dL (P = 0.32) were found between the 2 groups. FBG = fasting blood glucose; NS = not significant; NR = not reported; FAA = fast-acting analogue; RHI = regular human insulin; BG = blood glucose; SMBG = self-monitored blood glucose; od = once-daily; bd = twice-daily; NR = not reported; NPH = neutral protamine Hagedorn insulin; glargine = insulin glargine.