Introduction
Insulin aspart is a rapid-acting human insulin analog used in the management of diabetes mellitus. As a biosynthetic insulin, it was developed through recombinant DNA technology to provide faster onset and shorter duration of action compared to regular human insulin, making it particularly suitable for mealtime glucose control.
Mechanism of Action
Insulin aspart exerts its effects by binding to insulin receptors on target cells, primarily in muscle, liver, and adipose tissue. This binding activates the receptor's tyrosine kinase activity, initiating a cascade of intracellular signaling that promotes glucose uptake, glycogen synthesis, lipogenesis, and protein synthesis. The molecular modification (substitution of proline with aspartic acid at position B28) reduces self-association into hexamers, allowing for more rapid dissociation into monomers and consequently faster absorption from subcutaneous tissue.
Indications
- Treatment of type 1 diabetes mellitus in adults and pediatric patients
- Treatment of type 2 diabetes mellitus in adults
- Continuous subcutaneous insulin infusion (CSII) via insulin pumps
- Use in combination with longer-acting insulins for basal-bolus regimens
Dosage and Administration
Route: Subcutaneous injection (abdomen, thigh, buttocks, or upper arm) or continuous subcutaneous infusion Dosing:- Individualized based on metabolic needs, blood glucose monitoring, and glycemic control目标
- Typically administered 5-15 minutes before meals
- Initial dosing often starts at 0.2-0.4 units/kg/day for type 1 diabetes
- Divided doses typically provide 50-70% of total daily insulin requirement as mealtime insulin
- Renal impairment: Requires careful dose titration and monitoring
- Hepatic impairment: Reduced insulin requirements may be necessary
- Elderly: Conservative initial dosing with gradual titration
- Pregnancy: Category B - requires careful glucose monitoring and dose adjustment
Pharmacokinetics
Absorption: Rapid subcutaneous absorption with onset of action within 15 minutes. Peak plasma concentration reached in 40-50 minutes. Distribution: Distributed throughout extracellular fluid. Does not significantly bind to plasma proteins. Metabolism: Metabolized primarily in liver and kidneys via insulin protease activity and insulin-specific reductase. Elimination: Half-life approximately 60-90 minutes. Duration of action is 3-5 hours. Cleared renally with less than 1% excreted unchanged in urine.Contraindications
- Hypersensitivity to insulin aspart or any component of the formulation
- During episodes of hypoglycemia
- Hypoglycemia unawareness without appropriate precautions
Warnings and Precautions
Boxed Warning: Risk of hypoglycemia - may be life-threatening- Requires careful blood glucose monitoring and dose adjustment
- Rotation of injection sites to prevent lipodystrophy
- Potential for hypokalemia
- Visual disturbances may occur with rapid glucose control improvement
- Not for intravenous administration except under medical supervision
- Special caution with concomitant use of medications that affect glucose metabolism
- Risk of weight gain
Drug Interactions
Medications that may increase hypoglycemia risk:- Oral antidiabetic agents
- ACE inhibitors
- Disopyramide
- Fluoxetine
- MAO inhibitors
- Pentoxifylline
- Salicylates
- Somatostatin analogs
- Sulfonamide antibiotics
- Corticosteroids
- Danazol
- Diuretics
- Sympathomimetics
- Phenothiazines
- Thyroid hormones
- Estrogens, progestins
- Nicotine
- Atypical antipsychotics
- Beta-blockers may mask hypoglycemia symptoms
- Alcohol may potentiate hypoglycemic effect
Adverse Effects
Common (>10%):- Hypoglycemia
- Injection site reactions (redness, swelling, itching)
- Weight gain
- Hypokalemia
- Lipodystrophy at injection site
- Peripheral edema
- Visual refractive changes
- Systemic allergic reactions
- Sodium retention
- Hypersensitivity reactions
Monitoring Parameters
- Blood glucose levels (preprandial, postprandial, and bedtime)
- HbA1c every 3-6 months
- Serum potassium levels in at-risk patients
- Weight changes
- Injection site examination
- Hypoglycemia symptoms and awareness
- Renal and hepatic function in patients with comorbidities
- Visual acuity in patients with retinopathy
Patient Education
- Proper injection technique and site rotation
- Timing of administration in relation to meals
- Recognition and management of hypoglycemia symptoms
- Importance of regular blood glucose monitoring
- Never skip meals when using mealtime insulin
- Carry glucose source for hypoglycemia treatment
- Proper storage of insulin (refrigerate unopened vials/pens, room temperature for in-use products)
- When to seek medical attention (severe hypoglycemia, illness, surgery)
- Travel considerations and time zone changes
- Sick day management guidelines
- Importance of wearing medical identification
References
1. American Diabetes Association. Standards of Medical Care in Diabetes - 2023. Diabetes Care. 2023;46(Suppl 1):S1-S291. 2. Plank J, et al. A double-blind, randomized, dose-response study investigating the pharmacodynamic and pharmacokinetic properties of the long-acting insulin analog detemir. Diabetes Care. 2005;28(5):1107-1112. 3. Home PD. The pharmacokinetics and pharmacodynamics of rapid-acting insulin analogs and their clinical consequences. Diabetes Obes Metab. 2012;14(9):780-788. 4. FDA Prescribing Information: NovoLog (insulin aspart) injection. 2022. 5. Hirsch IB. Insulin analogues. N Engl J Med. 2005;352(2):174-183. 6. Mathieu C, et al. Insulin aspart in the management of diabetes mellitus: a systematic review and meta-analysis. Diabetes Technol Ther. 2020;22(6):1-12. 7. Seaquist ER, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and The Endocrine Society. Diabetes Care. 2013;36(5):1384-1395.
This monograph provides general information and should not replace professional medical advice. Always consult with healthcare providers for personalized medical guidance.