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Clinical use of insulin degludec

Vora J

Key messages:

  • Insulin degludec (IDeg) is a novel basal insulin with improved pharmacokinetic and pharmacodynamic properties compared with insulin glargine (IGlar)
  • IDeg has a long half-life of 25 hours and a duration of action of >42 hours at steady state, providing a flat and stable blood glucose-lowering effect when injected once daily
  • Data from phase 3a clinical trials with a treat-to-target design in patients with type 1 and type 2 diabetes indicate that IDeg has similar efficacy to IGlar; however, compared with IGlar, IDeg was associated with reductions in the risk of overall and nocturnal hypoglycaemia, during the entire treatment period (9% and 26% risk reductions for overall and nocturnal hypoglycaemia, respectively), and during the maintenance period (16% and 32% risk reductions for overall and nocturnal hypoglycaemia, respectively)
  • Given its pharmacodynamic properties, IDeg offers a broad dosing window, allowing for flexible dose administration, if required
  • The unique pharmacokinetic profile of IDeg facilitates glycaemic control while minimizing the risk of nocturnal hypoglycaemia

Improved glycaemic control can reduce the risk of long-term-diabetes-related complications, particularly when achieved early in the course of the disease. At each stage of the disease, however, clinical inertia exists that prevents patients with inadequate glycaemic control from receiving intensified therapy that may help them reach their glycaemic targets. Insulin therapy, in particular, is often underutilized in patients with type 2 diabetes due to the fear of hypoglycaemia and the burden of complex or inflexible dosing regimens.

IDeg is a new-generation basal insulin analogue that is designed to have a prolonged duration of action and less variability in its pharmacodynamic properties when compared with first-generation basal insulins. After subcutaneous administration, IDeg dihexamers form a stable depot of multihexamer chains at the injection site. The gradual dissociation of readily-absorbed IDeg monomers from the depot provides slow and continuous delivery of IDeg into circulation. At steady state, IDeg has a half-life of approximately 25 hours, and the resulting duration of action at steady state exceeds 42 hours, which is considerably longer than the 20.5-hour mean duration of action of IGlar.

The clinical safety and efficacy of IDeg has been evaluated in a large clinical development programme involving over 11,000 patients with type 1 or type 2 diabetes. Evidence from phase 3a clinical trials with a treat-to-target design in patients with type 1 and type 2 diabetes has shown that IDeg has similar efficacy to IGlar. In addition, in a pooled analysis, treatment with IDeg was associated with reductions in the risk of overall and nocturnal hypoglycaemia during both the entire treatment period (9% and 26% risk reductions for overall and nocturnal hypoglycaemia, respectively) and the maintenance period (16% and 32% risk reductions for overall and nocturnal hypoglycaemia, respectively).

In a pre-specified meta-analysis of major adverse cardiovascular events (MACE), treatment-emergent MACE was reported in 80 of the 8,918 patients involved in clinical trials of either IDeg or the co-formulation of IDeg and fast-acting insulin aspart (IDegAsp); from the 80 patients included, 53 were treated with IDeg or IDegAsp and 27 were treated with comparator basal insulin. The incidence rates were 1.48 events per 100 patient-years of exposure (PYE) in patients treated with IDeg or IDegAsp and 1.44 events per 100 PYE in patients treated with comparators. Post-hoc analyses of MACE data in clinical trials were then conducted. As these data neither confirmed nor excluded the possibility for an increased cardiovascular risk with IDeg in comparison with IGlar, the DEVOTE clinical trial was subsequently initiated to better define the cardiovascular profiles of IDeg and IDegAsp in patients at high risk of cardiovascular events.

IDeg is licensed for the treatment of adult patients with type 1 and type 2 diabetes. In patients with type 1 diabetes, IDeg should be administered once daily in combination with a prandial fast-acting insulin to provide insulin coverage during mealtimes. In patients with type 2 diabetes, IDeg can be administered alone, or in combination with oral hypoglycaemic agents, glucagon-like peptide-1 (GLP-1) analogues, or bolus insulin, as supported by clinical evidence.

One important feature of IDeg is flexible dosing. Ideally, IDeg should be administered once daily, preferably at the same time every day. However, if administration at the same time of day is not possible, the daily IDeg dose can be either advanced or postponed to accommodate different patient lifestyles, with no negative impact on glycaemic control, provided a minimum interval of 8 hours is maintained between IDeg injections. 

Selected article

On this page you have access to a selected article and a summary. This belongs to a series of 3 recently published articles specially curated for this course by Professor Xavier Cos. These articles cover the patterns of clinical treatment in type 2 diabetes and the new generation of long-acting insulins, their safety and efficacy profiles.


 

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