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
Nandu Thalange, Larry Deeb, Georgeanna Klingensmith, Denise R Franco, Lars Bardtrum, Deniz Tutkunkardas, Thomas Danne, Nandu Thalange, Larry Deeb, Georgeanna Klingensmith, Denise R Franco, Lars Bardtrum, Deniz Tutkunkardas, Thomas Danne
Abstract
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.
Keywords: hyperglycemia; insulin degludec/insulin aspart; insulin detemir; ketosis; type 1 diabetes.
Conflict of interest statement
N.T. reports payments for speaking and advising in the field of diabetes and to attend conferences and industry‐sponsored events from a number of companies, including Novo Nordisk. His former institution (Norfolk & Norwich University Hospital, UK) receives funding for the conduct of clinical trials. He was Signatory Investigator for two Novo Nordisk‐sponsored international RCTs (including Study 1 in this paper) as well as Principal Investigator for several studies in the diabetes field. No relevant financial interests/shareholdings L.B. reports no relevant conflicts of interest. G.K. reports consultancy fees for Novo Nordisk, Boehringer‐Ingelheim, Takeda, and AstraZeneca. D.R.F. reports grants in clinical trials and personal fees as speaker and advisory board from Abbott, BD, Janssen, Lilly, Novo Nordisk, Sanofi, Bayer, and Boehringer Ingelheim. L.B. and D.T. are employees and shareholders in Novo Nordisk A/S. T.D. reports grants from Boehringer Ingelheim, AstraZeneca, Roche, Insulet, Abbot, and DexCom.
© 2019 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.
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Source: PubMed