Insulin degludec in combination with bolus insulin aspart is safe and effective in children and adolescents with type 1 diabetes

Abstract

Insulin degludec (IDeg) once-daily was compared with insulin detemir (IDet) once- or twice-daily, with prandial insulin aspart in a treat-to-target, randomized controlled trial in children 1–17 yr with type 1 diabetes, for 26 wk (n = 350), followed by a 26-wk extension (n = 280). Participants were randomized to receive either IDeg once daily at the same time each day or IDet given once or twice daily according to local labeling. Aspart was titrated according to a sliding scale or in accordance with an insulin:carbohydrate ratio and a plasma glucose correction factor. Randomization was age-stratified: 85 subjects 1–5 yr. (IDeg: 43), 138 6–11 yr (IDeg: 70) and 127 12–17 yr (IDeg: 61) were included. Baseline characteristics were generally similar between groups overall and within each stratification. Non-inferiority of IDeg vs. IDet was confirmed for HbA1c at 26 wk; estimated treatment difference (ETD) 0.15% [−0.03; 0.32]95%CI. At 52 wk, HbA1c was 7.9% (IDeg) vs. 7.8% (IDet), NS; change in mean FPG was −1.29 mmol/L (IDeg) vs. +1.10 mmol/L (IDet) (ETD −1.62 mmol/L [−2.84; −0.41]95%CI, p = 0.0090) and mean basal insulin dose was 0.38 U/kg (IDeg) vs. 0.55 U/kg (IDet). The majority of IDet treated patients (64%) required twice-daily administration to achieve glycemic targets. Hypoglycemia rates did not differ significantly between IDeg and IDet, but confirmed and severe hypoglycemia rates were numerically higher with IDeg (57.7 vs. 54.1 patient-years of exposure (PYE) [NS] and 0.51 vs. 0.33, PYE [NS], respectively) although nocturnal hypoglycemia rates were numerically lower (6.0 vs. 7.6 PYE, NS). Rates of hyperglycemia with ketosis were significantly lower for IDeg vs. IDet [0.7 vs. 1.1 PYE, treatment ratio 0.41 (0.22; 0.78)95%CI, p = 0.0066]. Both treatments were well tolerated with comparable rates of adverse events. IDeg achieved equivalent long-term glycemic control, as measured by HbA1c with a significant FPG reduction at a 30% lower basal insulin dose when compared with IDet. Rates of hypoglycemia did not differ significantly between the two treatment groups; however, hyperglycemia with ketosis was significantly reduced in those treated with IDeg.

A randomized crossover study of the efficacy and safety of switching from insulin glargine to insulin degludec in children with type 1 diabetes

“…The 2-year extension of the main BEGIN trial [22] indicated that the hypoglycemia-reducing benefits of IDeg were observed at night, rather than during the day; this is likely because a relationship exists between bolus insulin and diurnal hypoglycemia, whereas the ultra-long acting and less variable glucose-lowering effects of IDeg may better decrease nocturnal hypoglycemia. Some other studies [9,13,[17][18][19][23][24][25][26], including our recent study [14], also demonstrated a greater reduction in the risk of nocturnal hypoglycemia, rather than an overall decrease, with IDeg in all-aged patients with type 1 diabetes. The outcomes of an earlier 1-year study of IDeg in Japanese adults with type 2 diabetes were consistent with our observations [11].…”

“…In addition, the majority of the studies have reported comparable glucose-lowering effects of IDeg and IGlar in patients with type 1 diabetes, as demonstrated by equivalent FPG and HbA1c levels [9,13,[17][18][19]. As mentioned in the introduction, in a 26-week study of pediatric patients with type 1 diabetes of all ages, Thalange et al [13] reported the non-inferiority of IDeg as compared with IDet in regard with changes in HbA1c levels from the baseline. On the other hand, we previously demonstrated an improvement in glycemic control in young adults with type 1 diabetes after changing from IGlar to IDeg [14].…”

“…Several studies in adults have shown that IDeg exhibits the desired optimal pharmacokinetic properties and confers a low risk of hypoglycemia in patients with both type 1 and type 2 diabetes [9][10][11]16]. In addition, the majority of the studies have reported comparable glucose-lowering effects of IDeg and IGlar in patients with type 1 diabetes, as demonstrated by equivalent FPG and HbA1c levels [9,13,[17][18][19]. As mentioned in the introduction, in a 26-week study of pediatric patients with type 1 diabetes of all ages, Thalange et al [13] reported the non-inferiority of IDeg as compared with IDet in regard with changes in HbA1c levels from the baseline.…”

“…Biester et al [12] demonstrated that the advantage of ultra-long pharmacokinetics of IDeg observed in adult patients were sustained in pediatric patients with type 1 diabetes. As for the clinical effect of IDeg in pediatric patients with type 1 diabetes, Thalange et al [13] demonstrated the non-inferiority of IDeg to insulin detemir (IDet) with respect to improvement of HbA1c levels; however, the frequencies of overall and severe hypoglycemia were numerically higher with IDeg, despite numerically lower frequencies of nocturnal hypoglycemia with once-daily administration of IDeg. Furthermore, we recently reported improvement of glycemic control, assessed by fasting plasma glucose (FPG) and HbA1c levels and decrease in the We initially set the dose of IDeg to be the same dose as IGlar when changed, but were then titrated to achieve self-monitored FPG levels of 90-140 mg/ dL.…”

Efficacy and safety of switching from insulin glargine to insulin degludec in young people with type 1 diabetes

“…Biester et al [16] reported only that the ultra-long pharmacokinetic properties of IDeg observed in adults were retained in children and adolescents with type 1 diabetes. Recently, Thalange et al [17] reported that IDeg offered glycemic control and frequencies of hypoglycemia similar to those achieved with La of insulin detemir (IDet), but reduced hyperglycemia with ketosis at a once-daily daily injection when used in these age groups of patients with type 1 diabetes.…”