Insulin Degludec + Insulin Aspart Premixed

Insulin Degludec + Insulin Aspart Premixed is indicated for the management of diabetes mellitus in adults and children as follows:

Approved Indications:

• Type 1 Diabetes Mellitus (T1DM):
  For patients requiring both basal and prandial insulin coverage, especially those who need flexibility in dosing schedule.
• Type 2 Diabetes Mellitus (T2DM):
  For patients inadequately controlled with oral antidiabetic medications or requiring insulin therapy, including those transitioning from other insulin regimens.

Clinically Accepted Off-Label Uses:

• Management of gestational diabetes in selected cases under strict clinical supervision.
• Inpatient hyperglycemia management when both basal and rapid insulin coverage is needed, though continuous monitoring is required.

General Principles:

• Administer subcutaneously in the thigh, upper arm, or abdomen.
• Do not mix with other insulin products in the same syringe.
• Rotate injection sites to reduce lipodystrophy risk.

Adults:

• Initial dose: Individualized based on previous insulin regimen and blood glucose levels.
• Twice daily dosing (morning and evening) is commonly recommended with meals.
• Titration: Adjust based on fasting and postprandial glucose monitoring, typically in increments of 2–4 units.

Pediatrics (≥1 year):

• Dose individualized according to body weight, prior insulin use, and blood glucose.
• Close monitoring is essential during therapy initiation and dose adjustments.

Elderly:

• Initiate at lower doses due to risk of hypoglycemia and possible renal impairment.
• Frequent glucose monitoring is recommended.

Special Populations:

• Renal Impairment: Dose adjustment may be required; start lower than usual.
• Hepatic Impairment: Initiate cautiously; monitor glucose levels frequently.
• Transition from Other Insulins: Calculate total daily insulin requirement and split according to basal/bolus ratio as per physician guidance.

Insulin Degludec is an ultra-long-acting basal insulin analog, providing a steady, peakless insulin level over 24 hours, which reduces fasting glucose levels. Insulin Aspart is a rapid-acting insulin analog that mimics physiological postprandial insulin peaks, reducing post-meal hyperglycemia. The premixed formulation combines these two actions, offering both basal and prandial glucose control. Degludec forms multi-hexamers after injection, releasing insulin slowly, while Aspart remains monomeric for rapid absorption, collectively achieving stable glycemic control throughout the day.

• Absorption:
  Aspart: Rapidly absorbed with peak action in 1–3 hours.
  Degludec: Slowly absorbed, providing a flat profile over 24–42 hours.
• Distribution: Widely distributed in extracellular fluid; protein binding is minimal for Aspart and moderate for Degludec.
• Metabolism: Both insulin components are metabolized in the liver and kidneys via proteolytic degradation into amino acids.
• Elimination: Excreted primarily by renal pathways; half-life: Aspart ~1 hour, Degludec ~25 hours.
• Onset of Action: Aspart ~10–20 minutes; Degludec ~30–90 minutes.
• Duration: Premixed action covers both prandial spikes and basal needs over 24 hours.

• Pregnancy:
  Insulin is the preferred agent for glycemic control in pregnancy; premixed insulin is used under strict monitoring. No teratogenic effects reported with Degludec or Aspart, but data in pregnancy are limited.
• Lactation:
  Both components are compatible with breastfeeding. Minimal transfer into breast milk; monitor infant for hypoglycemia.
• Caution: Adjust dose based on frequent glucose monitoring in both pregnancy and lactation.

• Primary Class: Antidiabetic Agent
• Subclass: Insulin analog, premixed basal-bolus insulin

• Known hypersensitivity to Insulin Degludec, Insulin Aspart, or any excipients.
• Severe hypoglycemia or history of recurrent hypoglycemia.
• Diabetic ketoacidosis unless concomitant insulin therapy is required.

• Hypoglycemia Risk: Monitor glucose frequently; higher risk in renal/hepatic impairment, elderly, or when combined with other hypoglycemic agents.
• Allergic Reactions: Rare anaphylaxis possible; discontinue if severe reaction occurs.
• Fluid Retention/Heart Failure: Monitor in patients on thiazolidinediones.
• Injection Site Reactions: Lipodystrophy may occur; rotate sites.
• Monitoring: Regular blood glucose and HbA1c assessments; ketone testing if hyperglycemia persists.

Common:

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

Less Common:

• Edema
• Allergic reactions
• Lipodystrophy at injection sites

Rare/Severe:

• Severe hypoglycemia with neuroglycopenic symptoms
• Anaphylactic reactions

• Hypoglycemic agents: Sulfonylureas, meglitinides — may increase hypoglycemia risk.
• Beta-blockers: May mask hypoglycemia symptoms.
• CYP450 interaction: Minimal; insulin is degraded proteolytically, not via CYP enzymes.
• Alcohol: May potentiate or reduce hypoglycemic effect.
• Corticosteroids, thiazide diuretics: Can reduce insulin effectiveness.

• Premixed Degludec/Aspart approved for use in T1DM and T2DM with flexible dosing schedules.
• Recent guidelines emphasize individualized basal-bolus regimens and glucose monitoring to reduce hypoglycemia risk.
• Shift toward using Degludec analogs for patients needing ultra-long basal insulin to minimize nocturnal hypoglycemia.

• Temperature: Store 2°C–8°C (refrigerated); do not freeze.
• Room Temperature Use: Can be kept at ≤30°C for up to 8 weeks.
• Light Protection: Keep in original pen/vial; protect from direct sunlight.
• Handling: Roll the pen gently before use; do not shake vigorously.
• Reconstitution: Not required; solution is clear and ready-to-use.