Insulin Degludec in Type 1 Diabetes

Abstract

OBJECTIVEInsulin degludec (IDeg) is a basal insulin that forms soluble multihexamers after subcutaneous injection, resulting in an ultra-long action profile. We assessed the efficacy and safety of IDeg formulations administered once daily in combination with mealtime insulin aspart in people with type 1 diabetes.RESEARCH DESIGN AND METHODSIn this 16-week, randomized, open-label trial, participants (mean: 45.8 years old, A1C 8.4%, fasting plasma glucose [FPG] 9.9 mmol/L, BMI 26.9 kg/m2) received subcutaneous injections of IDeg(A) (600 μmol/L; n = 59), IDeg(B) (900 μmol/L; n = 60), or insulin glargine (IGlar; n = 59), all given once daily in the evening. Insulin aspart was administered at mealtimes.RESULTSAt 16 weeks, mean A1C was comparable for IDeg(A) (7.8 ± 0.8%), IDeg(B) (8.0 ± 1.0%), and IGlar (7.6 ± 0.8%), as was FPG (8.3 ± 4.0, 8.3 ± 2.8, and 8.9 ± 3.5 mmol/L, respectively). Estimated mean rates of confirmed hypoglycemia were 28% lower for IDeg(A) compared with IGlar (rate ratio [RR]: 0.72 [95% CI 0.52–1.00]) and 10% lower for IDeg(B) compared with IGlar (RR: 0.90 [0.65–1.24]); rates of nocturnal hypoglycemia were 58% lower for IDeg(A) (RR: 0.42 [0.25–0.69]) and 29% lower for IDeg(B) (RR: 0.71 [0.44–1.16]). Mean total daily insulin dose was similar to baseline. The frequency and pattern of adverse events was similar between insulin treatments.CONCLUSIONSIn this clinical exploratory phase 2 trial in people with type 1 diabetes, IDeg is safe and well tolerated and provides comparable glycemic control to IGlar at similar doses, with reduced rates of hypoglycemia.

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

“…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.…”

“…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 the present study, the daily dose of IDeg was numerically decreased, but did not significantly differ during the 24-week study period relative to the baseline; therefore, the administration of a conservative dose is recommended in children of age<15 years with type 1 diabetes upon switching from IGlar previously given once daily to IDeg. Subsequently, this dose can be adjusted according to the patient's blood glucose levels to avoid occurrence of hypoglycemia [9,11,18,19,[24][25][26]. The dose-adjustment could affect a risk of hypoglycemia.…”

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“…A total of 4275 patients were administered Degludec (1102 with T1DM and 3173 with T2DM). It was confirmed that a decrease in HbA 1c was the same in all trials in terms of all the compared products (insulin Detemir and insulin Glargine) [12][13][14].…”

“…Przeprowadzono 11 międzynarodowych, kontrolowanych, otwartych, randomizowanych, z grupami równoległymi, prowadzonych do osiągnięcia zakładanego celu, badań klinicznych trwających 26 lub 52 tygodnie, w których 4275 pacjentom podawano Degludec (1102 z cukrzycą typu 1 i 3173 z cukrzycą typu 2). Potwierdzono, że obniżenie HbA 1c było równoważne we wszystkich badaniach w odniesieniu do wszystkich produktów porównywanych (insulina Detemir i insulina Glargina) [12][13][14]. W metaanalizie obejmującej siedem badań prowadzonych do osiągnięcia zakłada-nego celu (treat to target) u pacjentów z cukrzycą typu 1 i typu 2 Degludec okazał się być skuteczniejszy pod względem mniejszej liczby potwierdzonych epizodów hipoglikemii wynikającej z leczenia i potwierdzonych hipoglikemii nocnych w porównaniu z insuliną bazową Glargina.…”