|Drug class||Insulin (long-acting)|
|Main uses||Type I and type II diabetes|
|Side effects||Low blood sugar, allergic reactions, pain at the site of injection, itchiness, rash, weight gain, lipodystrophy|
|US NLM||Insulin degludec|
|Chemical and physical data|
|Molar mass||6104.04 g·mol−1|
|(what is this?)|
Insulin degludec, under the brand name Tresiba is an long-acting insulin used to treat type I and type II diabetes. It once daily by injection under the skin. Onset of effects occur within 90 minutes and last for more than 42 hours. After a few days it has a steady effects at all hours.
Common side effects include low blood sugar, allergic reactions, pain at the site of injection, itchiness, rash, weight gain, and lipodystrophy. Other side effects may include low potassium. In pregnancy NPH insulin is preferred. It is a form of insulin made by recombinant DNA technology and than further modified.
Insulin degludec was approved for medical use in Europe in 2013 and the United States in 2015. In the United Kingdom a 300 unit pen costs the NHS about £9 as of 2021. In the United States this amount costs about 100 USD. In 2019, it was the 168th most commonly prescribed medication in the United States, with more than 3 million prescriptions. It is also available in combination with liraglutide.
The dose is adjusted based on blood sugar control.
People taking insulin degludec needed to take smaller doses of basal insulin than those taking insulin glargine U100, while achieving similar blood glucose levels. Insulin degludec also has the ability to be mixed with other insulins, thereby improving glycemic control. This cannot be done with some other long-acting insulins.
A significant side effect of insulin therapy is hypoglycemia. A meta-analysis of clinical trials published in July 2012 found 39 to 47.9 events of hypoglycemia (defined as blood glucose <56 mg/dL) per patient year, with higher rates in the more concentrated degludec formulation. Rates of nocturnal hypoglycemia ranged from 3.7 to 5.1 events per patient year.
Mechanism of action
Insulin degludec is an ultra-long acting insulin that, unlike insulin glargine, is active at a physiologic pH. The addition of hexadecanedioic acid via an amide linkage to lysine at the B29 position allows for the formation of multi-hexamers in subcutaneous tissues. This allows for the formation of a subcutaneous depot that results in slow insulin release into the systemic circulation.
Insulin degludec has an onset of action of 30–90 minutes (similar to insulin glargine and insulin detemir). There is no peak in activity, due to the slow release into systemic circulation. The duration of action of insulin degludec is longer than 24 hours.
When taken at the same time of day, this long (but under 48 hour) duration can result in an overlap from one dose to the next, resulting in greater insulin action then. if the overlap should be during sleep, there is a risk of lower blood sugar, so it is important to dose in the morning so that the overlap will be when users are eating and otherwise checking their blood sugar. The dose should be titrated during this overlap period as well.
It is a modified insulin that has one single amino acid deleted in comparison to human insulin, and is conjugated to hexadecanedioic acid via gamma-L-glutamyl spacer at the amino acid lysine at position B29.
Insulin degludec has been filed for registration in the United States. Novo Nordisk hopes to begin marketing the insulin analog in 2015 or 2016 after the completion of additional cardiac safety studies requested by the U.S. Food and Drug Administration (FDA) in February 2013. Insulin degludec received FDA approval 25 September 2015 and marketing began on 26 January 2016.
Society and culture
The cost of this medication in the U.S. is $363 (USD) for 10 ml subcutaneous solution 100 units/mL 
Given the treat-to-target nature of the BEGIN trial program, much of the health economic analysis of insulin degludec has focussed on short-term cost-effectiveness based on differences in insulin dosing and hypoglycemic event incidence rather than differences in glycemic control. The first cost-effectiveness analysis of this nature was conducted from a societal perspective in the Swedish setting in 2013, finding that insulin degludec would be cost-effective relative to insulin glargine in the treatment of type 1 diabetes, and type 2 diabetes as part of either a basal or basal-insulin regimen.
Type 1 diabetes
Insulin degludec was studied as an alternative to insulin glargine as part of a basal-bolus regimen in the BEGIN Basal-Bolus Type 1 trial. 629 patients with type 1 diabetes were randomized in a 3:1 ratio to either insulin degludec (n=472) or insulin glargine (n=157) in addition to mealtime insulin aspart. Patients in the degludec treatment arm were switched from their basal insulin to insulin degludec in a 1:1 ratio, with a 20-30% dose reduction in patients receiving multiple basal doses per day. After 52 weeks, patients treated with insulin degludec produced a similar reduction in HbA1c (0.40% vs. 0.39%) meeting the criteria for noninferiority. Adverse events were similar in the two treatment arms; however, rates of nocturnal hypoglycemia (between midnight and 6am) were 27% lower in patients treated with insulin degludec (3.91 vs. 5.22%,p=0.024). The reduction in the incidence of hypoglycemia was seen as a therapeutic benefit, as hypoglycemia is often a dose limiting toxicity in insulin therapy.
Type 2 diabetes
In the BEGIN Basal-Bolus Type 2 trial, insulin degludec was studied as an alternative to insulin glargine in patients with type 2 diabetes mellitus. 995 patients were randomized to receive either insulin degludec (n=755) or insulin glargine (n=251), in addition to either mealtime insulin aspart, metformin, and/or pioglitazone. Patients in this trial had an average HbA1c of 8.3–8.4%, and 49–50% were on a regimen consisting of basal-bolus insulin plus oral antidiabetic medications. After 52 weeks, insulin degludec was found to be noninferior to insulin glargine, providing a similar HbA1c lowering effect (−1.10 vs. −1.18%). Overall rates of hypoglycemia were significantly lower with insulin degludec (11.09 vs. 13.63%/yr, p=0.0359), including cases of nocturnal hypoglycemia (1.39 vs. 1.84%/yr, p=0.0399).
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