Degludec: A New Ultra-long Lasting Insulin

Jenna Gregory, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0SP.

Type 1 diabetes is characterised by a deficiency in insulin, which in the majority of cases is due to an autoimmune condition whereby the body attacks the beta cells of the islets of Langerhans in the pancreas responsible for insulin production. Due to the complete lack of insulin in the body, exogenous insulins must replace both basal levels of insulin and provide a meal-related bolus of insulin. Current therapy is therefore a combination of long-acting insulin to replace the basal requirements and a bolus of short-acting insulin with meals. This regime often results in hypoglycaemias particularly at night, as a consequence, diabetic patients are often afraid and demonstrate poor adherence to medication leading to disease complications manifesting later in life.

Degludec is an ultra-long lasting insulin with a half-life in the circulation of 25 hours (1), which is twice that of currently available insulins, making it an ideal candidate to provide adequate basal insulin levels. Moreover, as Degludec has a duration of action of over 40 hours (2), it is plausible that patients would be able to medicate less frequently using this drug, not only a benefit for the patient but also cost saving for the NHS.

Two studies published in the Lancet this week reveal that direct comparison of Degludec with a current long-acting insulin therapy, glargine, shows little difference in efficacy with regard to long-term glycaemic control (HbA1c measurements) in both type 1 and type 2 diabetes (3,4) and importantly no difference in adverse reactions, confirming its efficacy and safety as a treatment in this phase 3 clinical trial. Furthermore Degludec provided participants with better control over hypoglycaemias, particularly overnight, a major limitation of current insulin therapies (3). Whilst the trial was not blinded, due to the administration of these two agents being very different, the authors did use objective criteria to differentiate the two treatments, for example HbA1c and plasma glucose levels to confirm hypoglycaemias, which were unlikely to be affected by the patient’s knowledge of their treatment.

This data taken together demonstrate Degludec as a safe and equally efficacious alternative to current long-acting insulins like glargine. Whilst Degludec is not a revolutionary new treatment in the battle against diabetes, there is no doubt that improvements in current therapies, in particular the 25% reduction in nocturnal hypoglycaemias that Degludec boasts, may not only make a significant difference to the quality of life of a diabetic patient, but also reduce the likelihood of serious complications from their disease later in life, making this an important step forward in our therapeutic management of diabetes.

References: 

1. Heise T, Hovelmann U, Nosek L, Bottcher S, Granhall C, Hahhr H. Insulin degludec has a two-fold longer half-life and a more consistent pharmacokinetic profile than insulin glargine. Diabetes 2011; 60 (suppl 1A): LB11.

2. Jonassen I, Havelund S, Ribel U, et al. Insulin degludec is a new generation ultra- long acting basal insulin with a unique mechanism of protraction based on multi hexamer formation. Diabetes 2010; 59 (suppl 1): A11.

3. Heller S, Buse J, Fisher M, Garg S, Marre M, Merker L, Renard E, Russell-Jones D, Philotheou A, Francisco AM, Pei H, Bode B; BEGIN Basal-Bolus Type 1 Trial Investigators. Insulin degludec, an ultra-long acting basal insulin, versus insulin glargine in basal bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. Lancet 2012; 379: 1489-1497. 10.1016/S0140-6736(12)60204-9

4. Garber AJ, King AB, Del Prato S, Sreenan S, Balci MK, Muñoz-Torres M, Rosenstock J, Endahl LA, Francisco AM, Hollander P; NN1250-3582 (BEGIN BB T2D) Trial Investigators. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. Lancet 2012 Apr 21;379(9825):1498-507. doi:10.1016/S0140-6736(12)60205-0

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