What is the mechanism of Insulin degludec?

Insulin degludec is a long-acting basal insulin analog used to control blood sugar levels in individuals with diabetes. Unlike traditional insulins that have a shorter duration of action, insulin degludec offers a prolonged and consistent glucose-lowering effect, which can help in achieving better glycemic control with fewer fluctuations.

The mechanism of insulin degludec centers around its unique molecular structure, which distinguishes it from other insulin formulations. The key component lies in its modified amino acid chain. Insulin degludec differs from human insulin by the addition of a hexadecanedioic acid moiety to the lysine at position B29. This modification allows the insulin molecules to form multi-hexamers when injected subcutaneously. These multi-hexamers create a depot of insulin in the subcutaneous tissue, which slowly and continuously disassembles into monomers, releasing insulin gradually into the bloodstream.

Once in the bloodstream, insulin degludec functions similarly to endogenous insulin by binding to insulin receptors on the surface of cells. This binding triggers a series of intracellular processes, including the translocation of glucose transporter type 4 (GLUT4) to the cell membrane, enhancing the uptake of glucose into cells, particularly muscle and adipose tissues. Additionally, insulin degludec inhibits hepatic gluconeogenesis and glycogenolysis, reducing glucose production by the liver. These actions collectively lower blood glucose levels.

A notable feature of insulin degludec is its ultra-long duration of action, which can last up to 42 hours. This extended activity profile is due to the slow and continuous release of insulin monomers from the subcutaneous depot, leading to a more stable and predictable pharmacokinetic profile. As a result, insulin degludec can be administered once daily, providing flexibility in dosing times compared to other basal insulins.

Clinical studies have demonstrated that insulin degludec offers several benefits over other basal insulins. It has been shown to reduce the risk of nocturnal hypoglycemia, which is a common concern with other long-acting insulins. The stable and prolonged action of insulin degludec helps maintain consistent blood glucose levels throughout the day and night, minimizing the risk of both hyperglycemia and hypoglycemia.

Moreover, insulin degludec has been found to be effective in various populations, including individuals with type 1 and type 2 diabetes. Its flexible dosing schedule can be particularly advantageous for patients with unpredictable lifestyles or those who struggle with maintaining regular injection times.

In summary, the mechanism of insulin degludec involves its unique molecular structure that allows the formation of multi-hexamers in the subcutaneous tissue, providing a prolonged and steady release of insulin. This ensures a stable and predictable glucose-lowering effect, improving glycemic control with a reduced risk of hypoglycemia. Its ultra-long duration of action and flexible dosing make it a valuable option for individuals with diabetes seeking effective and convenient blood sugar management.