出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/02/12 12:15:40」(JST)
| Systematic (IUPAC) name | |
|---|---|
|
B29N(epsilon)-omega-carboxypentadecanoyl-gamma-L-glutamyl desB30 human insulin
|
|
| Clinical data | |
| Trade names | Tresiba |
| AHFS/Drugs.com | UK Drug Information |
| Legal status |
|
| Routes of administration |
Subcutaneous |
| Identifiers | |
| CAS Number | 844439-96-9 |
| ATC code | A10AE06 |
| PubChem | SID 124490467 |
| ChemSpider | none |
| KEGG | D09727 |
| Chemical data | |
| Formula | C274H411N65O81S6 |
| Molar mass | 6103.972 g/mol |
| (verify) | |
Insulin degludec (INN/USAN) is an ultralong-acting basal insulin analogue that was developed by Novo Nordisk under the brand name Tresiba.[1] It is administered via subcutaneous injection once daily to help control the blood sugar level of those with diabetes. It has a duration of action that lasts up to 42 hours (compared to 18 to 26 hours provided by other marketed long-acting insulins such as insulin glargine and insulin detemir), making it a once-daily basal insulin,[2][3][4] that is one that provides a base insulin level, as opposed to the fast and short acting bolus insulins.
Insulin degludec 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 is an ultra-long acting insulin that, unlike insulin glargine, is active at a physiologic pH. The addition of hexadecanedioic acid to lysine at the B29 position allows for the formation of multi-hexamers in subcutaneous tissues.[5] This allows for the formation of a subcutaneous depot that results in slow insulin release into the systemic circulation.[6]
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 reported as being longer than 24 hours.[5][7]
Studies have shown that patients taking insulin degludec needed to take significantly smaller doses of basal insulin than those taking insulin glargine, 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 using current long-acting insulins.[8][9] A physician involved in the trials was quoted as saying,
"This allows the creation of a novel formulation that retains the smooth control of a long-acting basal with rapid-acting mealtime control from insulin aspart. This 2-component insulin retains the ultralow risk characteristics of degludec with simultaneous mealtime coverage."[10]
Insulin degludec has been filed for registration in the United States.[11] 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.[12]
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.[13]
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 + 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).[14]
A significant side effect of insulin therapy is hypoglycemia. A meta-analysis of clinical trails published in July 2012 found 39-47.9 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 3.7-5.1 events per patient year.[7]
|coauthors= (help)|coauthors= (help)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
| リンク元 | 「インスリンデグルデク」 |