Usage
- Insulin Degludec is prescribed for Type 1 and Type 2 diabetes mellitus in adults, adolescents, and children aged 1 year and older to improve glycemic control. It is a long-acting basal insulin analog.
- Pharmacological Classification: Long-acting insulin analog, antidiabetic agent.
- Mechanism of Action: Insulin Degludec binds to the insulin receptor, mimicking the action of endogenous insulin. This leads to increased glucose uptake in peripheral tissues (muscle and fat) and decreased hepatic glucose production.
Alternate Names
- Insulin Degludec
- Brand Names: Tresiba, Ryzodeg 70/30 (in combination with insulin aspart)
How It Works
- Pharmacodynamics: Insulin Degludec forms multi-hexamers at the injection site, resulting in a slow, prolonged release of insulin monomers into the circulation. This provides a stable, basal level of insulin, reducing fluctuations in blood glucose.
- Pharmacokinetics:
- Absorption: Slow and prolonged absorption from the subcutaneous injection site due to the formation of multi-hexamers.
- Metabolism: Metabolized similarly to human insulin, primarily in the liver and kidneys.
- Elimination: Primarily renal elimination.
- Mode of Action: Binds to the insulin receptor, a tyrosine kinase receptor, triggering a cascade of intracellular signaling pathways. This leads to translocation of glucose transporters (GLUT4) to the cell membrane, facilitating glucose uptake. It also inhibits gluconeogenesis and glycogenolysis in the liver.
- Receptor Binding: Binds specifically to the insulin receptor.
- Elimination Pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
- Type 1 Diabetes: Initially, one-third to one-half of the total daily insulin requirement administered subcutaneously once daily. The remainder of the daily insulin dose should be administered as a bolus (rapid-acting) insulin with meals.
- Type 2 Diabetes (insulin naive): 10 units subcutaneously once daily.
- Type 2 Diabetes (current insulin users): Start at the same dose as the total daily long- or intermediate-acting insulin.
- Titrate dose every 3–4 days based on fasting plasma glucose (FPG) levels, aiming for a target FPG of 80–130 mg/dL. Maximum dose is determined by individual patient response.
Children (1 year and older):
- Type 1 or 2 Diabetes (insulin naive): Similar to adult dosing.
- Type 2 Diabetes (current insulin users): Initiate at 80% of the total daily long- or intermediate-acting insulin dose to minimize the risk of hypoglycemia. Adjust dosage based on metabolic needs, blood glucose monitoring, and glycemic control goals. For pediatric patients requiring less than 5 units daily, use the U-100 vial.
Special Cases:
- Elderly Patients: Close glucose monitoring is essential. Dosage adjustments may be necessary due to age-related changes in insulin sensitivity and renal function.
- Patients with Renal Impairment: Dosage reduction may be needed.
- Patients with Hepatic Dysfunction: Dosage reduction may be needed.
- Patients with Comorbid Conditions: Individualized dosage adjustments based on specific comorbid conditions (e.g., cardiovascular disease) and their impact on glucose metabolism.
Clinical Use Cases
Insulin Degludec is a basal insulin analog and is not typically used in acute settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Rapid-acting insulins are preferred in such cases for tighter glucose control.
Dosage Adjustments
Dosage adjustments may be necessary based on FPG levels, changes in insulin requirements (e.g., during illness, stress, pregnancy, or with weight changes), concomitant medications, and other factors influencing glucose metabolism.
Side Effects
Common Side Effects
- Hypoglycemia (low blood sugar)
- Injection site reactions (pain, redness, swelling)
- Lipodystrophy (changes in fat tissue at the injection site)
- Weight gain
- Peripheral edema (swelling in the hands and feet)
Rare but Serious Side Effects
- Severe hypoglycemia (loss of consciousness, seizures)
- Severe allergic reactions (anaphylaxis)
- Hypokalemia (low potassium levels)
Long-Term Effects
- Potential for weight gain with prolonged use
- Possible increased risk of cardiovascular events (though this is debated)
Adverse Drug Reactions (ADR)
- Anaphylaxis
- Severe hypoglycemia
Contraindications
- Hypoglycemia
- Hypersensitivity to insulin degludec or any of the excipients
Drug Interactions
- Other insulin products: May enhance the hypoglycemic effects.
- Hypoglycemic agents: Additive hypoglycemic effect.
- Hyperglycemic agents (e.g., corticosteroids): May reduce the hypoglycemic effect of insulin degludec.
- Beta-blockers: May mask symptoms of hypoglycemia.
- Alcohol: May increase the risk of hypoglycemia.
- Many other drug interactions exist; consult a comprehensive drug interaction resource.
Pregnancy and Breastfeeding
- Pregnancy: Can be used during pregnancy if clinically needed. Close monitoring of blood glucose is essential, and dosage adjustments are often required.
- Breastfeeding: Can be used during breastfeeding. No significant adverse effects on the infant are expected.
Drug Profile Summary
- Mechanism of Action: Binds to insulin receptors, increasing glucose uptake and decreasing hepatic glucose production.
- Side Effects: Hypoglycemia, injection site reactions, lipodystrophy, weight gain, edema.
- Contraindications: Hypoglycemia, hypersensitivity.
- Drug Interactions: Numerous drug interactions; consult a comprehensive resource.
- Pregnancy & Breastfeeding: Generally safe with monitoring and dosage adjustments.
- Dosage: Individualized based on patient factors and glucose targets.
- Monitoring Parameters: FPG, HbA1c, potassium levels.
Popular Combinations
- Insulin degludec + insulin aspart (Ryzodeg 70/30): Combines basal and bolus insulin in one injection.
- Insulin degludec + liraglutide (Xultophy 100/3.6): Combines basal insulin with a GLP-1 receptor agonist for improved glycemic control and weight management.
Precautions
- General Precautions: Screen for allergies, assess renal and hepatic function, monitor potassium levels, educate patients on hypoglycemia management.
- Specific Populations: See above sections on dosage for elderly, renal/hepatic impairment, pregnancy, and breastfeeding.
- Lifestyle Considerations: Encourage healthy diet, regular exercise, and smoking cessation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended starting dose of Insulin Degludec?
A: The recommended starting dose varies depending on the type of diabetes and prior insulin use. For insulin-naïve patients with type 2 diabetes, it is 10 units once daily. For type 1 diabetes or patients already on insulin therapy, the starting dose is generally the same as the total daily dose of their previous long- or intermediate-acting insulin. Pediatric dosing for current insulin users is typically started at 80% of the previous daily long-acting insulin dose.
Q2: How is Insulin Degludec administered?
A: Insulin Degludec is administered subcutaneously once daily, into the thigh, abdomen, or upper arm. Rotate injection sites to avoid lipodystrophy.
Q3: When should Insulin Degludec be taken?
A: Adults can inject Tresiba at any time of day, but it should be at the same time each day. Children should inject it at the same time every day.
Q4: What should a patient do if they miss a dose of Insulin Degludec?
A: Patients should take the missed dose as soon as they remember, and then resume their usual once-daily dosing schedule, ensuring at least 8 hours between injections. For pediatric patients, they should contact their healthcare provider for guidance and monitor their blood glucose levels more frequently.
Q5: What are the major drug interactions with Insulin Degludec?
A: Insulin Degludec interacts with numerous medications, including other antidiabetic agents, corticosteroids, beta-blockers, and alcohol. Consult a comprehensive drug interaction resource for a complete list.
Q6: Can Insulin Degludec be used during pregnancy and breastfeeding?
A: Yes, Insulin Degludec can be used during pregnancy and breastfeeding, but careful monitoring of blood glucose is crucial, and dosage adjustments are often necessary.
Q7: What is the difference between Insulin Degludec and other basal insulins like Insulin Glargine?
A: Insulin Degludec has a longer duration of action than Insulin Glargine, providing a more stable and predictable basal insulin level. This may result in fewer episodes of hypoglycemia.
Q8: What is the maximum dose of Insulin Degludec?
A: The maximum dose is determined by individual patient response and is titrated based on blood glucose control.
Q9: What are the symptoms of severe hypoglycemia and what should be done if it occurs?
A: Severe hypoglycemia can manifest as confusion, seizures, loss of consciousness, and even death. If severe hypoglycemia occurs, administer glucagon if the patient is unable to take oral glucose, and seek immediate medical attention.
Q10: What are the signs of an allergic reaction to Insulin Degludec?
A: Allergic reactions can range from mild skin reactions (rash, itching) to severe anaphylaxis (difficulty breathing, swelling of face/throat). Seek immediate medical attention if signs of a severe allergic reaction occur.
