Usage
- Insulin Degludec + Liraglutide is prescribed as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is typically used when blood sugar levels are not adequately controlled by other medications, including basal insulin or liraglutide alone. It is not indicated for type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
- Pharmacological Classification: Antidiabetic combination; Long-acting insulin and GLP-1 receptor agonist.
- Mechanism of Action: This combination drug works through two distinct mechanisms:
- Insulin Degludec: A long-acting basal insulin analog that lowers blood glucose by facilitating glucose uptake into peripheral tissues (muscle and fat) and inhibiting hepatic glucose production.
- Liraglutide: A glucagon-like peptide-1 (GLP-1) receptor agonist that increases glucose-dependent insulin secretion, suppresses glucagon secretion, slows gastric emptying, and may reduce appetite.
Alternate Names
- International Nonproprietary Name (INN): Insulin degludec/liraglutide
- Brand Name: Xultophy
How It Works
- Pharmacodynamics: The combination of insulin degludec and liraglutide provides complementary effects on glycemic control. Insulin degludec provides a stable basal insulin level, while liraglutide enhances glucose-dependent insulin secretion, suppresses glucagon, and slows gastric emptying, reducing postprandial glucose excursions.
- Pharmacokinetics:
- Absorption: Administered subcutaneously, both components are absorbed into the systemic circulation. Insulin degludec forms soluble multi-hexamers at the injection site, resulting in slow and prolonged absorption, providing a steady basal insulin level for approximately 24 hours. Liraglutide absorption is also delayed due to its self-association property and slow release from the subcutaneous depot.
- Metabolism: Insulin degludec is metabolized primarily at the injection site and in peripheral tissues, similar to human insulin. Liraglutide is metabolized by dipeptidyl peptidase-4 (DPP-4) and other proteolytic enzymes, resulting in smaller peptides and amino acids.
- Elimination: The metabolites of both components are eliminated through renal and hepatic pathways.
Dosage
Standard Dosage
Adults:
- Initial Dose (naïve to basal insulin or GLP-1 RA): 10 units insulin degludec/0.36 mg liraglutide subcutaneously once daily.
- Initial Dose (currently on basal insulin or GLP-1 RA): 16 units insulin degludec/0.58 mg liraglutide subcutaneously once daily.
- Titration: Adjust dose by 2 units every 3-4 days based on fasting plasma glucose, aiming for target levels. Maximum daily dose is 50 units insulin degludec/1.8 mg liraglutide.
Children:
- Not recommended for use in patients under 18 years of age. Safety and efficacy have not been established in this population.
Special Cases:
- Elderly Patients (≥ 65 years): Initiate with conservative dosing and titrate cautiously due to increased risk of hypoglycemia. Enhanced glucose monitoring is recommended. Limited experience in patients ≥ 75 years.
- Patients with Renal Impairment: Intensified glucose monitoring and individual dose adjustment are necessary. Not recommended for patients with moderate to severe renal impairment or end-stage renal disease.
- Patients with Hepatic Dysfunction: Limited experience; use with caution. Closely monitor glucose levels.
- Patients with Comorbid Conditions: Individualized dosing and monitoring are essential.
Clinical Use Cases
Insulin Degludec + Liraglutide is not specifically indicated for use in clinical settings such as intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. Its primary use is for the long-term management of type 2 diabetes. For these acute care settings, short-acting insulins and other appropriate glucose management strategies are typically employed.
Side Effects
Common Side Effects
- Nasopharyngitis, upper respiratory tract infection
- Headache
- Nausea, diarrhea, vomiting, constipation
- Injection site reactions
Rare but Serious Side Effects
- Pancreatitis (acute or chronic): Severe abdominal pain radiating to the back, nausea, vomiting, fever.
- Hypoglycemia: Tremors, sweating, confusion, dizziness, loss of consciousness.
- Hypersensitivity reactions (including anaphylaxis and angioedema): Hives, difficulty breathing, swelling of face, lips, tongue, or throat.
- Gallbladder disease: Severe stomach pain, fever, nausea, vomiting.
- Renal impairment: Decreased urine output, swelling in ankles or feet.
- Thyroid C-cell tumors (in rodents; unknown risk in humans).
Contraindications
- Hypersensitivity to insulin degludec, liraglutide, or any component of the formulation.
- Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).
- Episodes of hypoglycemia.
Drug Interactions
- Medications affecting glucose metabolism: May require dose adjustments of Insulin Degludec + Liraglutide.
- Drugs delaying gastric emptying: Liraglutide may affect the absorption of oral medications.
- Examples:
- Antidiabetic agents (e.g., sulfonylureas, insulin)
- Beta-blockers
- Corticosteroids
- Thiazide diuretics
- Alcohol
Pregnancy and Breastfeeding
- Pregnancy: Limited human data; potential risk based on animal studies with liraglutide (increased embryofetal death and fetal abnormalities). Generally, insulin is preferred for managing diabetes during pregnancy. Weigh benefits against risks.
- Breastfeeding: Both components are excreted in animal milk; unknown if excreted in human milk. Exercise caution. Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need and potential adverse effects on the infant.
Popular Combinations
- Metformin + Insulin Degludec + Liraglutide: Often used in patients not achieving adequate control with metformin and Insulin Degludec + Liraglutide alone.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Insulin Degludec + Liraglutide?
A: See “Dosage” section above for detailed dosage information, including adjustments for various patient populations.
Q2: What are the common side effects?
A: Common side effects include nasopharyngitis, headache, nausea, diarrhea, and injection site reactions.
Q3: Is Insulin Degludec + Liraglutide safe in pregnancy?
A: Limited human data; potential risk based on animal studies with liraglutide. Generally, insulin is preferred for managing diabetes during pregnancy. Weigh benefits against risks.
Q4: Can this medication be used with other antidiabetic drugs?
A: Yes, but careful monitoring and dose adjustment may be necessary.
Q5: What should be done if a dose is missed?
A: If a dose is missed, resume the usual once-daily regimen with the next scheduled dose. If more than 3 days have elapsed, consult a physician before resuming.
Q6: Are there any specific monitoring parameters for patients on this drug?
A: Regular blood glucose monitoring, HbA1c, renal function, and liver function tests as needed. Monitor potassium levels in patients at risk for hypokalemia.
Q7: Can patients with renal or hepatic impairment use this drug?
A: Caution is advised in patients with hepatic impairment. Dose adjustments and increased monitoring are usually necessary for patients with mild renal impairment, but not recommended for moderate to severe renal impairment or end-stage renal disease.
Q8: What are the contraindications to using Insulin Degludec + Liraglutide?
A: Contraindications include hypersensitivity to the components, personal/family history of MTC or MEN 2, and episodes of hypoglycemia.
Q9: Can Insulin Degludec + Liraglutide be used in patients with type 1 diabetes?
A: No, it is not indicated for type 1 diabetes or diabetic ketoacidosis. It is specifically approved for type 2 diabetes mellitus.
