The rate of hyperglycemia and ketosis with insulin degludec-based treatment compared with insulin detemir in pediatric patients with type 1 diabetes: An analysis of data from two randomized trials.
Adolescent
Blood Glucose
/ metabolism
Child
Child, Preschool
Clinical Trials, Phase III as Topic
/ statistics & numerical data
Diabetes Mellitus, Type 1
/ blood
Diabetic Ketoacidosis
/ epidemiology
Drug Combinations
Female
Humans
Hyperglycemia
/ epidemiology
Hypoglycemia
/ chemically induced
Infant
Insulin Aspart
/ administration & dosage
Insulin Detemir
/ administration & dosage
Insulin, Long-Acting
/ administration & dosage
Male
Randomized Controlled Trials as Topic
/ statistics & numerical data
Retrospective Studies
hyperglycemia
insulin degludec/insulin aspart
insulin detemir
ketosis
type 1 diabetes
Journal
Pediatric diabetes
ISSN: 1399-5448
Titre abrégé: Pediatr Diabetes
Pays: Denmark
ID NLM: 100939345
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
21
08
2018
revised:
07
11
2018
accepted:
29
11
2018
pubmed:
23
1
2019
medline:
29
10
2019
entrez:
23
1
2019
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
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).
OBJECTIVE
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).
SUBJECTS
Patients (aged 1-17 years inclusive) with T1D treated with insulin for ≥3 months.
METHODS
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.
RESULTS
Despite similar rates of hyperglycemia with degludec/IDegAsp compared with IDet, the rates of ketosis were lower with degludec/IDegAsp.
CONCLUSIONS
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.
Identifiants
pubmed: 30666772
doi: 10.1111/pedi.12821
pmc: PMC6849556
doi:
Substances chimiques
Blood Glucose
0
Drug Combinations
0
Insulin, Long-Acting
0
insulin degludec, insulin aspart drug combination
0
Insulin Detemir
4FT78T86XV
insulin degludec
54Q18076QB
Insulin Aspart
D933668QVX
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
314-320Informations de copyright
© 2019 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.
Références
Pediatr Diabetes. 2015 May;16(3):164-76
pubmed: 25683037
Pediatr Diabetes. 2011 Jun;12(4 Pt 1):307-12
pubmed: 21466644
Diabetes Ther. 2014 Jun;5(1):255-65
pubmed: 24888255
Pediatr Diabetes. 2014 Sep;15 Suppl 20:102-14
pubmed: 25182311
Pediatr Diabetes. 2018 Nov;19(7):1263-1270
pubmed: 30014589
Pediatr Diabetes. 2014 Sep;15 Suppl 20:193-202
pubmed: 25182314
Pediatr Diabetes. 2013 Dec;14(8):541-53
pubmed: 24119040
Pediatr Diabetes. 2019 May;20(3):314-320
pubmed: 30666772
Pediatr Diabetes. 2003 Jun;4(2):77-81
pubmed: 14655263
Diabetes Care. 2015 Oct;38(10):1876-82
pubmed: 26283737
Diabetes Ther. 2010 Dec;1(2):103-20
pubmed: 22127748