Insulin Aspart + Insulin Degludec (Ryzodeg® 70/30)

Usage

• Medical Conditions: Insulin Aspart + Insulin Degludec is prescribed for Type 1 and Type 2 diabetes mellitus to improve glycemic control in adults. It is not recommended for the treatment of diabetic ketoacidosis.
• Pharmacological Classification: Antidiabetic Agent, Rapid-acting/Long-acting Insulin Combination.
• Mechanism of Action: This combination provides both basal (background) and prandial (mealtime) insulin coverage. Insulin degludec is an ultra-long-acting basal insulin analog that forms multi-hexamers at the injection site, resulting in slow and prolonged release into the circulation. Insulin aspart is a rapid-acting insulin analog that starts working quickly to cover the glucose rise after meals. Both insulins work by binding to insulin receptors on cells, facilitating glucose uptake and utilization, thus lowering blood glucose levels.

Alternate Names

• Insulin Degludec/Insulin Aspart
• IDegAsp
• Brand Names: Ryzodeg® 70/30

How It Works

• Pharmacodynamics: Both insulin degludec and insulin aspart exert their glucose-lowering effects by binding to insulin receptors on target cells. This binding initiates a cascade of intracellular events, including increased glucose transport into cells, glycogen synthesis, protein synthesis, and lipogenesis. Degludec provides a stable, flat, and prolonged glucose-lowering effect, lasting beyond 42 hours, while aspart provides a rapid onset of action for postprandial glucose control.
• Pharmacokinetics:
  • Absorption: Insulin degludec is absorbed slowly and continuously from the subcutaneous injection site due to its multi-hexamer formation. Insulin aspart is absorbed rapidly.
  • Metabolism: Both insulins are metabolized primarily in the liver and kidneys.
  • Elimination: The metabolites of both are eliminated via renal and hepatic routes.
• Mode of Action: Receptor binding to the insulin receptor.
• Elimination Pathways: Primarily renal and hepatic.

Dosage

Standard Dosage

Adults:

• Initial Dose: For insulin-naive patients, the starting dose is one-third to one-half of the total daily insulin requirement, administered once daily with the main meal. The remaining insulin requirement is covered with rapid-acting insulin at other meals. For insulin-experienced patients, the starting dose is the same as the previous basal insulin dose, also administered once daily with the main meal. Rapid-acting insulin is continued at the same dose for meals not covered by Ryzodeg. A common starting dose for insulin-naive patients with type 2 diabetes is 10 units once daily.
• Maintenance Dose: Adjust the dose every 3-4 days based on fasting blood glucose measurements, aiming for individualized glycemic targets. Dose adjustments are typically made in 2-unit increments.

Children (1-17 years):

• Type 1 DM: Similar to adults, one-third to one-half of the total daily insulin dose with the main meal, supplemented with rapid-acting insulin at other meals. A usual initial dose range is 0.2-0.4 units/kg.
• Type 2 DM: 10 units subcutaneously once daily with the main meal.
• Safety Considerations: Safety and efficacy not established in children under 1 year of age. Not recommended for pediatric patients requiring <5 units daily.

Special Cases:

• Elderly Patients: Start with a lower dose and titrate cautiously due to increased sensitivity to hypoglycemia.
• Patients with Renal Impairment: Dose adjustments may be necessary due to potential for reduced clearance.
• Patients with Hepatic Dysfunction: Monitor closely and adjust dose as needed.
• Patients with Comorbid Conditions: Consider individual patient needs and risks of hypoglycemia.

Clinical Use Cases

Ryzodeg is not recommended for:

• Intubation
• Surgical Procedures
• Mechanical Ventilation
• Intensive Care Unit (ICU) Use
• Emergency Situations

Its use in these settings needs specific assessment and management, potentially requiring intravenous insulin.

Dosage Adjustments

Dose adjustments may be required based on factors like:

• Renal/hepatic dysfunction
• Intercurrent illness
• Changes in diet or exercise
• Concomitant medications

Side Effects

Common Side Effects

• Hypoglycemia
• Injection site reactions (redness, swelling, itching)
• Weight gain

Rare but Serious Side Effects

• Severe hypoglycemia (loss of consciousness, seizures)
• Allergic reactions (anaphylaxis)
• Hypokalemia

Long-Term Effects

• Lipodystrophy (changes in fat tissue at injection site)
• Peripheral edema

Adverse Drug Reactions (ADR)

• Severe hypoglycemia
• Anaphylaxis

Contraindications

• Hypersensitivity to insulin degludec, insulin aspart, or any excipients
• Episodes of hypoglycemia

Drug Interactions

• Other Antidiabetic Agents: Additive hypoglycemic effects.
• Corticosteroids: Reduced insulin effectiveness.
• Beta-blockers: May mask symptoms of hypoglycemia.
• Thiazide diuretics, Thyroid hormone: May raise blood glucose levels and require insulin dose adjustments.
• Alcohol: Can increase the risk of hypoglycemia.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: B3 (Australian categorization - safety not established. Data limited).
• Fetal Risks: While insulin is generally preferred for diabetes management in pregnancy, the safety of this specific combination is not established.
• Breastfeeding: Excretion in breast milk unknown, safety not established.

Drug Profile Summary

• Mechanism of Action: Dual-action insulin providing basal and prandial glucose control.
• Side Effects: Hypoglycemia, injection site reactions, weight gain.
• Contraindications: Hypersensitivity, hypoglycemia.
• Drug Interactions: Other antidiabetic agents, corticosteroids, beta-blockers.
• Pregnancy & Breastfeeding: Safety and efficacy not established.
• Dosage: Individualized based on patient needs and glucose monitoring.
• Monitoring Parameters: Fasting and postprandial blood glucose, HbA1c.

Popular Combinations

Ryzodeg is sometimes used in combination with other oral antidiabetic agents (e.g., metformin, DPP-4 inhibitors, SGLT2 inhibitors) when additional glycemic control is needed.

Precautions

• General Precautions: Careful insulin label checking, proper injection technique, education about hypoglycemia.
• Specific Populations: Close monitoring and dose adjustment in elderly, renal/hepatic impairment, and pregnancy (if used).
• Lifestyle Considerations: Diet, exercise, and alcohol consumption can affect insulin requirements.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Insulin Aspart + Insulin Degludec?

A: The dosage is individualized based on the patient’s metabolic needs, blood glucose levels, and glycemic control goal. For insulin-naive Type 2 DM patients, a common starting dose is 10 units once daily with the largest meal. For insulin-experienced patients, start with the same dose units as their total daily basal insulin.

Q2: How should Ryzodeg be administered?

A: Ryzodeg is administered subcutaneously once or twice daily, immediately before a main carbohydrate-containing meal.

Q3: What are the common side effects of Ryzodeg?

A: The most common side effect is hypoglycemia. Other side effects include injection site reactions and weight gain.

Q4: Can Ryzodeg be used during pregnancy?

A: The safety and efficacy of Ryzodeg have not been established in pregnancy. The decision to use this medication should be made on a case-by-case basis after assessing potential benefits and risks.

Q5: How does Ryzodeg differ from other insulin therapies?

A: Ryzodeg combines ultra-long-acting and rapid-acting insulin in a single injection, providing both basal and prandial coverage. This can simplify insulin regimens and potentially reduce the risk of nocturnal hypoglycemia compared with some other regimens.

Q6: What should I do if my patient experiences hypoglycemia while taking Ryzodeg?

A: Treat hypoglycemia according to standard protocols (e.g., consumption of fast-acting carbohydrates). Patients should be educated on how to recognize and manage hypoglycemia.

Q7: Are there any drug interactions I should be aware of with Ryzodeg?

A: Yes, several drugs can interact with Ryzodeg, such as other antidiabetic agents, corticosteroids, and beta-blockers. Always review a patient’s medication list for potential interactions.

Q8: Can Ryzodeg be used in patients with renal or hepatic impairment?

A: Ryzodeg can be used with caution in these patients, but close monitoring and dose adjustment might be necessary.

Q9: What are the key monitoring parameters for patients on Ryzodeg?

A: Monitor fasting and postprandial blood glucose levels regularly, along with HbA1c every 3 months, to assess glycemic control and adjust dosage as needed.