insulin-degludec and Diabetic-Ketoacidosis

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.

Topics: Adolescent; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Infant; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting

Insulin degludec (IDeg) is the longest-acting basal insulin available. Whether IDeg compared to shorter-acting basal insulins like insulin glargine U100 (IGlarU100) reduces the rate of diabetic ketoacidosis (DKA) in adolescents with type 1 diabetes is unknown.. We hypothesized that adolescents with type 1 diabetes would have lower DKA rates and mean hemoglobin A1c (HbA1c) when using IDeg as compared to IGlarU100.. To avoid selection bias, we used self-control case series methodology. Adolescents with type 1 diabetes treated for DKA from January 2015 through December 2018 who switched basal insulin from IGlarU100 to IDeg were eligible for analysis. Thirty-five patients were included, each acting as their own control. Mean HbA1c and DKA rate for the 12 months prior to and after switching to IDeg were compared.. Mean HbA1c prior to and after switching to IDeg was unchanged (97 ± 20 vs. 97 ± 21 mmol/mol [11.0 ± 1.8 vs. 11.0 ± 1.9%]). Median DKA rate (admissions/year) while on IGlar-U100 was 1 with an interquartile range (IQR) of 1-2. After switching to IDeg, median DKA admission rate remained 1, however the IQR decreased to 0-1 (one-sided p value 0.0004). Median change in DKA rate was 1 fewer admission per year, with a maximum reduction of 3 admissions. Higher baseline rates of DKA increased the odds of a patient reducing his/her DKA rate by 1 admission per year or more.. Using IDeg for basal insulin in adolescent patients may decrease the rate of DKA relative to IGlarU100 despite no improvement in HbA1c and may be cost-effective.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Retrospective Studies

Historically, data on the rate of hyperglycemia and ketosis have not been collected in clinical trials. However, it is clinically important to assess the rate of these events in children with type 1 diabetes (T1D). This question was addressed in two pediatric trials using insulin degludec (degludec).. To assess the rate of hyperglycemia and ketosis in two-phase 3b trials investigating degludec (Study 1) and degludec with insulin aspart (IDegAsp [Study 2]) vs insulin detemir (IDet).. Patients (aged 1-17 years inclusive) with T1D treated with insulin for ≥3 months.. Study 1: patients were randomized to degludec once daily (OD) or IDet OD/twice daily (BID) for 26 weeks, followed by a 26-week extension phase. Study 2: patients were randomized to IDegAsp OD or IDet OD/BID for 16 weeks. Bolus mealtime IAsp was included in both studies. In Study 1, hyperglycemia was recorded if plasma glucose (PG) was >11.1 mmol/L, with ketone measurement required with significant hyperglycemia (>14.0 mmol/L). In Study 2, hyperglycemia was recorded with PG >14.0 mmol/L where the subject looked/felt ill, with ketone measurement also required in these hyperglycemic patients. In this post hoc analysis, the hyperglycemia threshold was 14.0 mmol/L for uniformity.. Despite similar rates of hyperglycemia with degludec/IDegAsp compared with IDet, the rates of ketosis were lower with degludec/IDegAsp.. These trials, the first to systematically collect data on ketosis in pediatric patients with T1D, demonstrate the potential of degludec/IDegAsp to reduce rates of metabolic decompensation, compared with IDet.

Topics: Adolescent; Blood Glucose; Child; Child, Preschool; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Drug Combinations; Female; Humans; Hyperglycemia; Hypoglycemia; Infant; Insulin Aspart; Insulin Detemir; Insulin, Long-Acting; Male; Randomized Controlled Trials as Topic; Retrospective Studies