The Food and Drug Administration (FDA) has recently approved two insulin injection products that contain insulin degludec, a long lasting basal insulin that can be used by people with either Type 1 or Type 2 diabetes. It has a duration of action that lasts for up to 42hrs and offers diabetic patients a much greater flexibility of use than other products that are currently available on the market. It is available in two strengths – 100 units/ml and 200 units/ml. It is given once daily, preferably at the same time of day, with a minimum of 8 hours to be observed between injections.

Is there anybody for whom insulin degludec is not suitable?

Although relatively new to the market and with little formal research on all patient groups, it is thought that products containing insulin degludec may not be suitable for people that experience reactions to glycerol, metacresol, phenol or zinc acetate.

What is the evidence base underpinning the use of insulin degludec? Is there any comparative data with existing diabetes treatment options?

There is a growing body of evidence regarding the use of insulin degludec in patients with both Type 1 and Type 2 diabetes. In terms of glycaemic control in Type 1 diabetes, degludec is non-inferior when compared to insulin glargine but it has statistically significant lower rates of nocturnal hypoglycaemia (1). There is a single 104 week study that measured and evaluated safety data relating to the use of degludec (2), although there are no comparative studies comparing it with NPH (isophane) insulin. Similarly, there are, as yet, no studies that measure patient-orientated efficacy outcomes. The results of two Randomised Controlled Trials (RCTs) have shown degludec to reduce glycated haemoglobin (HbA1c) by between 0.1-0.4% points from baseline (also non-inferior when compared to insulin glargine) (3). In regards to Type 2 diabetes, insulin degludec has also been evidenced to reduce HbA1c by approximately 1.1% from baseline (4). In two open label RCTs comparing glycaemic control, both insulin degludec and insulin glargine were shown to reduce HbA1c by a similar degree. In one of the studies, insulin degludec was also shown to significantly reduce the rate of overall hypoglycaemia, nocturnal hypoglycaemia and (in a post-hoc analysis) daytime hypoglycaemia, compared with insulin glargine (5). In another, it was shown to significantly reduce nocturnal hypoglycaemia and severe hypoglycaemia (6). However, because of the small number of studies and low event rates, it is advised that the results are approached with caution until more studies are undertaken and the results can be corroborated on a bigger scale. An additional RCT has been undertaken that compares the efficacy of insulin degludec with sitagliptin in a population who are insulin naive, finding that degludec was superior in terms of glycaemic control but resulted in a greater number of overall confirmed episodes of hypoglycaemia (7).

Are there any patient groups who would be likely to be benefit the most from insulin degludec?

The long acting nature of degludec means it is an excellent alternative for a number of different patients. It could be a preferred option for patients who operate with a greater degree of flexibility in their lives, such as patients who regularly play sports, those who have complex and erratic lifestyles, work shifts, or frequently travel by air and regularly cross time zones. The dose of insulin that patients require is dependent on a number of additional factors such as body weight, level of insulin deficiency and treatment response. Most guidelines for patients with type 2 diabetes tend to promote the initial use of human isophane insulin, injected once or twice daily according to individual need. Where this is not possible, basil insulin regimens that contain insulin degludec (used to keep blood glucose levels consistent during periods of fasting) may be recommended in conjunction with oral glucose-lowering drugs. This could be due to a number of factors, including the individual being overweight/obese and insulin resistant, a reluctance to begin treatment (because only one injection is typically required per day), and individuals who do not have the ability to inject themselves as required (i.e. an elderly housebound patient who required assistance from a healthcare professional).

Is insulin degludec going to be made more widely available for the treatment of diabetes?

Like all new additions to the market, there are a number of different considerations that local healthcare decision makers would need to make in making insulin degludec a more widely available treatment option. It is currently more expensive than other basal insulin products that are tried and tested and display a similar efficacy record. As other forms of insulin have been on the market for longer, they also generally have a stronger safety record due to being well researched and understood from a clinical and pharmaceutical perspective. Any decisions to prescribe will most likely be influenced by the characteristics of individual patients who do not always manage their diabetes very well, and their personal experience of hypoglycaemia, so the introduction of insulin degludec is more likely to be trialled on specific individuals and population subgroups than rolled out across the whole population affected by diabetes. The position of insulin degludec in the marketplace may be strengthened once its impact is better understood, and further well designed studies are undertaken.

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REFERENCES:

1. NICE / Type 1 Diabetes : insulin degludec. Available online at https://www.nice.org.uk/advice/esnm24/chapter/key-points-from-the-evidence (last accessed 4th October 2015)
2. Heller S, Buse J, Fisher M et al (2012) Insulin degludec, an ultra-longacting 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 379: 1489–97
3. Mathieu C, Hollander P, Miranda-Palma B et al. (2013) Efficacy and safety of insulin degludec in a flexible dosing regimen vs insulin glargine in patients with type 1 diabetes (BEGIN: Flex T1): a 26-week randomized, treat-to-target trial with a 26-week extension J Clin Endo Meta 98: 1154–62
4. Zinman B, Philis-Tsimikas A, Cariou B et al (2012) Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes: a 1-year, randomized, treat-to-target trial (BEGIN Once Long) Diabetes Care 35: 2464–71
5. Garber AJ, King AB, Del Prato S et al (2012) 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 379: 1498–507
6. Mathieu C, Hollander P, Miranda-Palma B et al. (2013) Efficacy and safety of insulin degludec in a flexible dosing regimen vs insulin glargine in patients with type 1 diabetes (BEGIN: Flex T1): a 26-week randomized, treat-to-target trial with a 26-week extension J Clin Endo Meta 98: 1154–62
7. Philis-Tsimikas A, Del Prato S, Satman I et al (2013) Effect of insulin degludec versus sitagliptin in patients with type 2 diabetes uncontrolled on oral antidiabetic agents Diabetes, Obesity and Metabolism 15: 760–6