Insulin degludec
[CAS# 844439-96-9]

Identification

• Classification: Biological >> Proteins and peptides >> Hormone
• Name: Insulin degludec
• Synonyms: 16-[[(1S)-4-[[(5S)-5-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[2-[[(1R,6R,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R,47R,50S,53S,56S,59S,62S,65S,68S,71S,74R,77S,80S,83S,88R)-88-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[(2-aminoacetyl)amino]-3-methylpentanoyl]amino]-3-methylbutanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]-6-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-methylbutanoyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-methylpentanoyl]amino]-47-[[(1S)-3-amino-1-carboxy-3-oxopropyl]carbamoyl]-53-(2-amino-2-oxoethyl)-62-(3-amino-3-oxopropyl)-77-[(2S)-butan-2-yl]-24,56-bis(2-carboxyethyl)-83-[(1R)-1-hydroxyethyl]-12,71,80-tris(hydroxymethyl)-33,50,65-tris[(4-hydroxyphenyl)methyl]-15-(1H-imidazol-4-ylmethyl)-27-methyl-18,30,36,59,68-pentakis(2-methylpropyl)-7,10,13,16,19,22,25,28,31,34,37,40,49,52,55,58,61,64,67,70,73,76,79,82,85,87-hexacosaoxo-21,39-di(propan-2-yl)-3,4,44,45,90,91-hexathia-8,11,14,17,20,23,26,29,32,35,38,41,48,51,54,57,60,63,66,69,72,75,78,81,84,86-hexacosazabicyclo[72.11.7]dononacontane-42-carbonyl]amino]acetyl]amino]-4-carboxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-carboxypentyl]amino]-1-carboxy-4-oxobutyl]amino]-16-oxohexadecanoic acid
• Molecular Formula: C₂₇₄H₄₁₁N₆₅O₈₁S₆
• Molecular Weight: 6103.97
• CAS Registry Number: 844439-96-9
• SMILES: CC[C@H](C)[C@H]1C(=O)N[C@H]2CSSC[C@@H](C(=O)N[C@@H](CSSC[C@@H](C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC2=O)CO)CC(C)C)CC3=CC=C(C=C3)O)CCC(=O)N)CC(C)C)CCC(=O)O)CC(=O)N)CC4=CC=C(C=C4)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CC5=CC=CC=C5)C(=O)N[C@@H](CC6=CC=CC=C6)C(=O)N[C@@H](CC7=CC=C(C=C7)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N8CCC[C@H]8C(=O)N[C@@H](CCCCNC(=O)CC[C@@H](C(=O)O)NC(=O)CCCCCCCCCCCCCCC(=O)O)C(=O)O)C(C)C)CC(C)C)CC9=CC=C(C=C9)O)CC(C)C)C)CCC(=O)O)C(C)C)CC(C)C)CC2=CNC=N2)CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC2=CC=CC=C2)N)C(=O)N[C@H](C(=O)N[C@H](C(=O)N1)CO)[C@@H](C)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)CN

Discovory and Applicatios

Insulin degludec is a long-acting basal insulin analog that has been developed to provide stable and prolonged blood glucose control in patients with diabetes. Its molecular design, which includes modifications to the insulin structure, allows for an extended duration of action compared to traditional insulin formulations. The discovery of insulin degludec was part of ongoing efforts to create insulin therapies that can mimic the natural, steady release of insulin in the body, reducing the frequency of injections and the risk of hypoglycemia.

The unique structure of insulin degludec includes an addition of a hexadecanedioic acid chain, which facilitates the formation of multi-hexamer complexes in subcutaneous tissue. These complexes slowly dissociate, releasing insulin monomers gradually into the bloodstream. This prolonged release mechanism allows insulin degludec to have an ultra-long duration of action, lasting up to 42 hours, making it suitable for once-daily administration at any time of the day, offering flexibility in dosing schedules.

Clinically, insulin degludec has been widely used in the treatment of both type 1 and type 2 diabetes. Its extended action profile and low variability in insulin levels throughout the day help patients maintain stable glycemic control, with fewer fluctuations in blood sugar levels. This reduces the risk of nocturnal hypoglycemia, a common concern for diabetes patients on long-acting insulin therapies. Additionally, the flexibility in timing reduces the burden on patients, improving adherence to treatment regimens.

Insulin degludec has been shown to be effective in combination with other antidiabetic agents, such as mealtime insulins or oral medications. This combination therapy provides comprehensive glucose control throughout the day and night, addressing both fasting and postprandial glucose levels. Its pharmacokinetic profile has been instrumental in helping patients achieve better glycemic targets with a reduced risk of complications compared to older insulin analogs.

The development of insulin degludec represents a significant advancement in diabetes management, offering patients improved quality of life and more reliable control over their condition. Its long-lasting and stable profile makes it an essential option in the therapeutic arsenal for diabetes treatment.

References

2012. Degludec: A Novel Basal Insulin. Recent Patents on Endocrine, Metabolic & Immune Drug Discovery, 6(1).
DOI: 10.2174/187221412799015326

2020. Pharmacokinetic and Pharmacodynamic Head-to-Head Comparison of Clinical, Equivalent Doses of Insulin Glargine 300 units � mL-1 and Insulin Degludec 100 units � mL-1 in Type 1 Diabetes. Diabetes Care, 44(2).
DOI: 10.2337/dc20-1033

2021. Insulin Doses Requirements in Patients with Type 1 Diabetes Using Glargine U300 or Degludec in Routine Clinical Practice. Journal of Investigative Medicine, 69(5).
DOI: 10.1136/jim-2020-001633