Efficacy and safety of insulin degludec given as part of basal-bolus treatment with mealtime insulin aspart in type 1 diabetes: a 26-week randomized, open-label, treat-to-target non-inferiority trial.
OBJECTIVE
The efficacy and safety of insulin degludec (IDeg) was compared with insulin detemir (IDet), both administered once daily (OD) as basal treatment in participants with type 1 diabetes mellitus (T1DM). The primary outcome was non-inferiority of IDeg to IDet in glycated haemoglobin (HbA1c) reduction after 26 weeks.


METHODS
This multinational, 26-week, controlled, open-label, parallel-group trial randomized adults with T1DM to IDeg or IDet as OD basal insulin treatment combined with mealtime bolus insulin aspart (IAsp). Participants with T1DM treated with any basal-bolus insulin regimen for ≥ 12 months prior to the trial, a mean HbA1c ≤ 10.0% (85.8 mmol/mol) and body mass index (BMI) ≤ 35.0 kg/m(2) at screening participated in the trial (IDeg: N = 302; IDet: N = 153).


RESULTS
After 26 weeks, HbA1c decreased 0.73% (8.0 mmol/mol) (IDeg) and 0.65% (7.1 mmol/mol) (IDet) [estimated treatment difference (ETD) IDeg-IDet: -0.09% (-0.23; 0.05)95% CI (-10.0 mmol/mol [-2.6; 0.6]95% CI ); confirming non-inferiority]. Mean fasting plasma glucose improved in both groups, and was lower with IDeg than IDet [ETD IDeg-IDet: -1.66 mmol/l (-2.37; -0.95)95% CI , p < 0.0001]. The rate of confirmed hypoglycaemia was similar with IDeg and IDet [45.83 vs. 45.69 episodes per patient-year of exposure (PYE); estimated rate ratio (RR) IDeg/IDet: 0.98 (0.80; 1.20)95% CI , p = 0.86]. The rate of nocturnal confirmed hypoglycaemia was lower with IDeg than IDet [4.14 vs. 5.93 episodes per PYE; RR IDeg/IDet: 0.66 (0.49; 0.88)95% CI , p = 0.0049]. Adverse event profiles were similar between groups.


CONCLUSIONS
IDeg administered OD in basal-bolus therapy effectively improved long-term glycaemic control in participants with T1DM with a lower risk of nocturnal confirmed hypoglycaemia than IDet.
Diabetes Research Centre, Leicester General Hospital, University of Leicester, Leicester, UK.
M J
MJ
Davies
J L
JL
Gross
Y
Y
Ono
T
T
Sasaki
G
G
Bantwal
M A
MA
Gall
M
M
Niemeyer
H
H
Seino
D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000187:drug effects*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D061267:Insulin Aspart / Q000008:administration & dosage*; D049528:Insulin, Long-Acting / Q000008:administration & dosage*; D008297:Male; D062407:Meals; D013997:Time Factors; D016896:Treatment Outcome
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D061267:Insulin Aspart; D049528:Insulin, Long-Acting; C517652:hemoglobin A1c protein, human; C571886:insulin degludec
glycaemic control; hypoglycaemia; insulin aspart; insulin degludec; insulin detemir; insulin therapy; type 1 diabetes mellitus