Insulin degludec forms soluble multi-hexamers upon subcutaneous injection, which act as a depot from which insulin monomers are gradually released. These monomers bind to the insulin receptor, resulting in the same pharmacological effects as human insulin.1
The glucose-lowering effect of insulin degludec lasts over 42 hours, allowing flexibility in the time of administration.1
Two phase III, randomised, treat-to-target non-inferiority studies evaluated the safety and efficacy of once-daily insulin degludec in comparison with once-daily insulin glargine, both in combination with mealtime short-acting insulin aspart: BEGIN Basal–Bolus Type 1 trial in patients with type I diabetes and BEGIN Basal–Bolus Type 2 trial in patients with type II diabetes. Participants in the second study also received metformin and/or pioglitazone.2,3
The primary outcome measure was the change from baseline in HbA1c, with a non-inferiority limit of -0.4% for the treatment difference after 52 weeks.2,3
Non-inferior to insulin glargine
The first study recruited patients (n=629) with type I diabetes who had been on a treatment regimen of basal–bolus insulin for at least a year and had an HbA1c ≤10%. After 52 weeks, patients treated with insulin degludec (n=472) experienced a reduction in HbA1c similar to that seen in patients who received insulin glargine (-0.40% vs -0.39%). The treatment difference of -0.01% (95% CI -0.14—0.11) met the prespecified non-inferiority criterion.2
Patients in the second study (n=1,006) had type II diabetes and had received insulin for at least three months before study entry, with an HbA1c of 7.0—10%. Insulin degludec produced a reduction in HbA1c of -1.06%, compared with a reduction of -1.19% with insulin glargine. The treatment difference was 0.08% (95% CI -0.05—0.21), meeting the pre-specified limit for non-inferiority.3
The most frequently reported adverse events in patients receiving insulin degludec were hypoglycaemia and injection site reactions. However, a pre-planned meta-analysis of the safety data from both studies showed that insulin degludec was associated with a lower rate than insulin glargine of overall hypoglycaemia in type II diabetes (estimated risk ratio 0.83) and nocturnal hypoglycaemia in both type I and type II diabetes (estimated risk ratio 0.74).1
No loss of efficacy after 12 months of treatment
A further one-year study, BEGIN Once Long, also compared the efficacy of insulin degludec with insulin glargine, this time both in combination with metformin, in 1,030 insulin-naïve patients with type II diabetes inadequately controlled on oral antidiabetic drugs.4
Insulin degludec was non-inferior to insulin glargine in improving glycaemic control, as indicated by similar reductions in HbA1c (1.06% vs 1.19%), with a treatment difference of 0.09% (95% CI -0.04—0.22). The number of episodes of hypoglycaemia per patient per year was similar in the two groups (1.52 with insulin degludec vs 1.85 with insulin glargine).4
Available in two strengths
Two strengths of Tresiba are available: 100 units/ml and 200 units/ml. These are delivered in two distinct 3ml FlexTouch pen devices: the light green 100 units/ml pen, which delivers insulin in steps of one unit (max 80 units per injection) and is supplied in a five-pen pack; and the dark green 200 units/ml pen, which delivers insulin in steps of two units (max 160 units per injection) and is supplied in a three-pen pack. Both pens have a dose-counter window that shows the exact dose dialled (ie, the number of units that will be injected regardless of strength).
Prescribers should always specify the strength of Tresiba on the prescription and patients should visually identify the strength of Tresiba they are dispensed. Patients should be advised to seek medical advice immediately if they administer an incorrect dose.
1. Tresiba Summary of Product Characteristics, January 2013.
2. Heller S et al. Lancet 2012; 379: 1489—97.
3. Garber A et al. Lancet 2012; 379: 1498—507.
4. Zinman B et al. Diabetes Care 2012; 35: 2464—71.
Further information: Novo Nordisk Ltd