ArticlesEfficacy and safety of insulin degludec three times a week versus insulin glargine once a day in insulin-naive patients with type 2 diabetes: results of two phase 3, 26 week, randomised, open-label, treat-to-target, non-inferiority trials
Introduction
Insulin degludec is a basal insulin analogue that forms a soluble depot of multihexamers after subcutaneous injection,1 resulting in a long half-life (about 25 h) and a consistent glucose-lowering effect that lasts longer than 42 h.2, 3, 4 Results of phase 3a treat-to-target trials in patients with type 1 and type 2 diabetes have shown that once-daily insulin degludec provides similar glycaemic control to insulin glargine but with lower rates of hypoglycaemia, particularly during the night.5, 6, 7, 8 Insulin degludec is approved for once-daily dosing in the European Union, Japan, and Mexico and is under regulatory review in other countries; the US Food and Drug Administration (FDA) has requested additional cardiovascular data from a dedicated cardiovascular outcomes trial before their review can be completed.
On the basis of the ultra-long pharmacokinetic and pharmacodynamic profile of insulin degludec, a three-times-weekly dosing regimen was explored in a 16 week, proof-of-concept phase 2, treat-to-target trial in patients with type 2 diabetes.9 In that trial, insulin degludec injected three times a week (IDeg 3TW) provided similar glycaemic control to once-daily insulin glargine (IGlar OD), with similar rates of hypoglycaemia.9 Because a three-times-weekly dosing schedule might, for some patients, be an appealing alternative to the once-daily dosing regimens required by basal insulin analogues, larger, phase 3 trials to further test this treatment and dosing schedule were deemed important.
The objective of this study was to analyse the data from two 26 week, phase 3 trials that compared the efficacy and safety of IDeg 3TW with IGlar OD in previously insulin-naive patients with type 2 diabetes inadequately controlled by oral antidiabetic (OAD) treatments.
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Study design and participants
Both phase 3 trials were of identical design (26 week, randomised, treat-to-target, two-arm, parallel group, and open-label), differing only in terms of whether insulin degludec was administered in the morning before the first meal of the day (AM trial) or with the main evening meal (PM trial). The AM trial was done at 94 sites in seven countries (Canada, Czech Republic, Israel, Slovakia, South Africa, UK, and USA) from February to November, 2010; the PM trial was done at 89 sites in seven
Results
Of the 705 participants screened in the AM trial, and the 677 participants screened in the PM trial, 460 (AM) and 467 (PM) were randomly assigned to treatment (figure 1). Similar proportions of participants completed treatment in each trial (figure 1). Within each trial, baseline and demographic characteristics in the full analysis set (ie, all randomised patients excluding one patient in the IDeg 3TWAM trial who was randomised in error) were well matched between groups, except for slight
Discussion
In both trials, clinically relevant improvements in long-term glycaemic control (HbA1c) were recorded for IGlar OD and IDeg 3TW, although the HbA1c reduction was greater with IGlar OD. Indeed, irrespective of whether insulin degludec was injected in the morning or evening, non-inferiority to IGlar OD with respect to change in HbA1c from baseline was not established. IDeg 3TW was also inferior to IGlar OD in terms of reductions from baseline in laboratory-measured FPG and SMBG concentrations.
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A Review of the Clinical Efficacy and Safety of Insulin Degludec and Glargine 300 U/mL in the Treatment of Diabetes Mellitus
2017, Clinical TherapeuticsCitation Excerpt :The results of the BEGIN Once Long trial and its extension showed that insulin degludec in combination with OADs provide safe and effective glycemic control, with a significantly lower risk of nocturnal hypoglycemia, for up to 2 years in patients with T2DM. Following the Phase II proof-of-concept study by Zinman et al18 were 2 Phase III studies, the BEGIN:EASY AM trial and the BEGIN:EASY PM trial, which assessed the efficacy and safety of insulin degludec given 3 times a week, either before breakfast or with the evening meal in patients with T2DM.23 Both trials were 26-week, randomized, multicenter, treat-to-target, 2-arm, parallel group, open-label studies, with the only difference being the time of insulin degludec administration.
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2017, Diabetes Research and Clinical PracticeCitation Excerpt :Even in studies with type 2 diabetes, non-inferiority to glargine was confirmed. This was shown in insulin-naïve [8,9,24,25] as well as in insulin-exposed subjects [7,9]. In our type 2 diabetes follow-up cohort, a significant decrease in HbA1C after starting with or switching to degludec was documented (Table 2).
Modern technologies for glucose monitoring and insulin replacement
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