What is the mechanism of action of Tresiba (insulin degludec)?

From the Guidelines

Tresiba is a suitable long-acting insulin option for patients with diabetes, particularly those who require a once-daily dosing regimen and have a high risk of hypoglycemia, as it has been shown to provide stable blood glucose control with less risk of overnight hypoglycemia compared to other long-acting insulins 1.

Key Considerations

• The standard starting dose for adults with type 2 diabetes is usually 10 units once daily, while those with type 1 diabetes might start with 1/3 to 1/2 of their total daily insulin requirement.
• Tresiba's main advantage is its ultra-long duration of action (up to 42 hours), which allows for flexible dosing times when needed.
• Side effects may include hypoglycemia, injection site reactions, allergic reactions, weight gain, and edema.
• Patients should monitor blood glucose regularly when using Tresiba and should not change their insulin regimen without consulting their healthcare provider.

Clinical Evidence

• A recent study published in Diabetes Care in 2023 found that longer-acting basal analogs, such as insulin degludec, may convey a lower hypoglycemia risk compared to U-100 glargine when used in combination with oral agents 1.
• Another study published in the same journal in 2022 found that basal insulin analogs have longer duration of action with flatter, more constant plasma concentrations and activity profiles than NPH insulin, which can reduce the risk of symptomatic and nocturnal hypoglycemia 1.

Patient Management

• Tresiba should be used as part of a comprehensive diabetes management plan that includes diet and exercise.
• Patients should be educated on the proper use of Tresiba, including dosing, administration, and potential side effects.
• Regular monitoring of blood glucose levels and adjustment of the insulin regimen as needed is crucial to achieve optimal glycemic control and minimize the risk of hypoglycemia.

From the FDA Drug Label

The primary activity of insulin, including TRESIBA, is regulation of glucose metabolism. Insulin and its analogs lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin also inhibits lipolysis and proteolysis, and enhances protein synthesis TRESIBA forms multi-hexamers when injected into the subcutaneous tissue resulting in a subcutaneous insulin degludec depot. The protracted time action profile of TRESIBA is predominantly due to delayed absorption of insulin degludec from the subcutaneous tissue to the systemic circulation and to a lesser extent due to binding of insulin degludec to circulating albumin.

Tresiba is a long-acting basal human insulin analog for subcutaneous injection.

• It has a molecular formula of C274H411N65O81S6 and a molecular weight of 6.104 kDa.
• The half-life after subcutaneous administration is determined primarily by the rate of absorption from the subcutaneous tissue, and is approximately 25 hours independent of dose.
• Degradation of TRESIBA is similar to that of insulin human; all metabolites formed are inactive.
• The mean apparent clearance of insulin degludec is 0.03 L/kg (2.1 L/h in 70 kg patient) after single subcutaneous dose of 0.4 units/kg 2.

From the Research

Tresiba Overview

• Tresiba, also known as insulin degludec, is an ultra-long-acting insulin analogue used in the management of diabetes mellitus 3.
• It has a flat, stable glucose-lowering profile with a duration of action of more than 42 hours, and less within-patient day-to-day variability in glucose-lowering effect than insulin glargine 3.

Efficacy and Safety

• Insulin degludec achieved similar glycaemic control to insulin glargine in patients with type 1 or 2 diabetes, but with a lower risk of nocturnal hypoglycaemia 3, 4.
• Trials have shown that insulin degludec may be an appropriate option for initiating insulin therapy in patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs 3, 5.
• Insulin degludec was associated with a significantly decreased fasting plasma glucose, with lower prevalences of overall and nocturnal hypoglycemia compared to other long-acting insulin analogues 6.

Clinical Trials

• The SWITCH 2 randomized clinical trial found that treatment with basal insulin degludec resulted in a reduced rate of overall symptomatic hypoglycemia compared to insulin glargine U100 in patients with type 2 diabetes 7.
• A systematic review and meta-analysis found that insulin degludec was associated with a significantly decreased rate of overall and nocturnal hypoglycemia compared to other long-acting insulin analogues 6.
• A 78-week study found that insulin degludec improved long-term glycaemic control similarly to insulin glargine, but with fewer hypoglycaemic episodes in patients with advanced type 2 diabetes on basal-bolus insulin therapy 5.