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

Abstract

AimsThe 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.MethodsThis 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/m2 at screening participated in the trial (IDeg: N = 302; IDet: N = 153).ResultsAfter 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.ConclusionIDeg 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.

Attributes Influencing Insulin Pen Preference Among Caregivers and Patients With Diabetes Who Require Greater Than 20 Units of Mealtime Insulin

“…9 Published real-life data from retrospective, [10][11][12] prospective observational, 13,14 and noninterventional studies 15 have identified patients with T2DM who report using more than 20 units of mealtime insulin per day. Likewise, pediatric 16 and adult patients with type 1 diabetes mellitus (T1DM) 17,18 have also reported using more than 20 units of mealtime insulin per day. As of 2012, more than 60% of all US patients with T2DM injecting mealtime insulin were taking more than 20 units of their mealtime insulin per day (mealtime defined as rapid-/ short-acting insulin; excludes pumpers); in Western Europe (EU5), the percentage was even higher (70% of all mealtime insulin-injecting patients with T2DM were taking 20 or more units of mealtime insulin per day).…”

A comparison of IDeg + IAsp versus IDet + IAsp in subjects with type 1 diabetes: subgroup analysis of Japanese subjects

“…The design, methodology and study procedures of the trial have been reported in full elsewhere [16]. In brief, the study was a 26-week, randomised, controlled, open-label, parallel-group, non-inferiority trial, with a treat-to-target design, in line with current Food and Drug Administration recommendations for the evaluation of novel insulin preparations [17].…”

“…Eligible participants were randomised 2:1 to either IDeg OD (Tresiba Ò , 100 U/mL) or IDet (Levemir Ò , 100 U/mL) as basal insulin, each in combination with mealtime IAsp (NovoRapid Ò , 100 U/mL) (all from Novo Nordisk, Bagsvaerd, Denmark). Participants transferred to their randomised treatment from their pretrial insulin (basal insulin) on a unit-to-unit basis, as described in the full trial report [16].…”

“…More recently, the efficacy and safety of IDeg in T1DM, given OD as part of a basal-bolus regimen with mealtime IAsp, were demonstrated in the global phase III BEGIN Basal-bolus Type 1 study (Brazil, Finland, India, Italy, Japan, Republic of Macedonia, UK) [16]. In this trial, patients receiving IDeg achieved improved long-term glycaemic control, with a lower risk of nocturnal confirmed hypoglycaemia compared with IDet [16].…”

“…In this trial, patients receiving IDeg achieved improved long-term glycaemic control, with a lower risk of nocturnal confirmed hypoglycaemia compared with IDet [16]. The current analysis was performed to assess whether the efficacy and safety of IDeg OD plus mealtime IAsp was maintained in a subpopulation of Japanese patients with T1DM from this trial.…”