Continuing Education Activity

Insulin aspart is a rapid-acting, human insulin analog that is FDA approved to treat type-1 and type-2 diabetes mellitus to improve glycemic control in adults and children. Insulin aspart may also be used to treat diabetic ketoacidosis (DKA), though this is not an FDA-approved indication. This activity outlines the indications, mechanism of action, safe administration, adverse effects, contraindications, monitoring, and toxicity of insulin aspart.

Objectives:

• Identify the appropriate indications for insulin aspart.
• Summarize the appropriate dosing of insulin aspart as part of a glycemic control regimen.
• Describe the potential adverse event profile and contraindications of insulin aspart.
• Outline interprofessional team strategies for improving care coordination and communication to advance appropriate clinical outcomes with insulin aspart therapy as part of a diabetes mellitus glycemic control treatment plan leading to optimal patient outcomes.

Indications

Insulin aspart is a rapid-acting, human insulin analog that is FDA approved for the treatment of type-1 and type-2 diabetes mellitus to improve glycemic control in adults and children. Insulin aspart may also be used to treat diabetic ketoacidosis (DKA), though this is not an FDA-approved indication.[1] Insulin aspart should be used in addition to a long-acting (basal) insulin for complete therapy unless used in a continuous subcutaneous (insulin pump) or intravenous insulin infusion.[2] Rapid-acting insulin products target-controlling, after-meal, blood glucose concentrations, or reducing blood glucose in response to an elevated blood glucose measurement, as in a correctional scale.[3]

Insulin aspart, or any rapid or short-acting insulin, is a mainstay of therapy in type-1 diabetes mellitus. Total daily insulin doses are usually between 0.4 to 1 units/kg per day, divided into long-acting insulin and rapid-acting insulin, such as insulin aspart. An initial breakdown of 50% basal insulin, 50% rapid-acting insulin is a starting place for most patients with type-1 diabetes mellitus and adjusted based on blood glucose. Doses are highly patient-specific. Type-2 diabetes mellitus patients often use more basal insulin than bolus insulin compared to type-1 diabetes mellitus patients.[4]

In type-2 diabetes mellitus, insulin aspart may be added for further glycemic control in addition to oral medications or long-acting insulin. Recommended starting doses for type-2 diabetes mellitus patients may be any of the following options: 4 units per meal, 0.1 units/kg per meal, or 10% of the basal dose. If hemoglobin A1c is less than 8%, consider reducing basal insulin dose when adding insulin aspart with meals.[5]

Insulin aspart is also available commercially in a combination product with insulin degludec (long-acting insulin) or insulin aspart protamine (intermediate action insulin). Insulin degludec plus insulin aspart is dosed once or twice a day with the main meal. Insulin-naive patients should start insulin degludec/insulin aspart at 0.2 to 0.4 units/kg per day. Insulin aspart/insulin aspart protamine is 30% insulin aspart, 70% insulin aspart protamine. Dosing for the protamine product starts at 0.5 units/kg per day, divided into two doses before meals with 70% of the total daily dose before breakfast and 30% of the total daily dose before dinner.[6]

Mechanism of Action

Insulin aspart regulates the metabolism of glucose. It promotes the storage and inhibits the breakdown of glucose, fat, and amino acids. Insulin lowers blood glucose by increasing peripheral glucose uptake, particularly in the skeletal muscle and fat. Insulin enhances the storage of fat (lipogenesis) and protein synthesis. Insulin aspart also inhibits gluconeogenesis (hepatic glucose production), lipolysis (breakdown of fat/lipids to fatty acids), and proteolysis (breakdown of proteins into amino acids). Maximum glucose-lowering effects are seen within 1 to 2 hours and endure for 3 to 5 hours. Insulin aspart is equipotent to regular insulin with a faster onset and shorter duration of action. Thus insulin aspart is preferred for mealtime insulin coverage as it can be administered up to every 4 hours.

Endogenous insulin is naturally produced by the pancreas, and insulin apart is manufactured through recombinant DNA technology using Saccharomyces cerevisiae expression system. Insulin aspart differs from endogenous insulin by containing aspartic acid instead of proline at position B28. Insulins as medications can be categorized as rapid-, short-, intermediate-, and long-acting depending on their pharmacologic effects, e.g., onset, peak, and duration.

Administration

Insulin aspart should be administered subcutaneously (SC) within 5 to 10 minutes before a meal, with 1 to 4 meals per day. To avoid lipodystrophy, rotate injection sites between the top of thighs, back of upper arms, buttocks, or abdomen. Avoid injecting within 2 inches of the naval. Insulin aspart may also be administered using a continuous subcutaneous infusion through an insulin pump or intravenously (IV) as a diluted solution with close monitoring of blood glucose and serum potassium. Insulin aspart may be mixed with NPH insulin only but may only be administered SC once mixed.

Adverse Effects

The primary adverse effect of insulin aspart is hypoglycemia, defined as blood glucose less than 70 mg/dL. Signs and symptoms of hypoglycemia include dizziness, light-headedness, sweating, confusion, headache, blurred vision, slurred speech, shakiness, tachycardia, irritability, or hunger.[7] Severe cases of hypoglycemia (blood glucose less than 30 mg/dL) may lead to seizures or death. Hypoglycemia is a dose-dependent adverse effect and can be avoided in the future with lower doses of insulin.[8] After any hypoglycemic event, insulin doses, and food (glucose) intake should be evaluated to adjust therapy and prevent future hypoglycemia.[9]

Additional adverse reactions may include allergic reactions, including local injection site reactions, lipodystrophy, rash, pruritus, and hypokalemia. Hypokalemia is dose-dependent, though the other additional adverse drug reactions are not dose-dependent.

Contraindications

Insulin aspart is contraindicated in patients with documented hypersensitivity to the drug or component of the formulation. It is also contraindicated during episodes of hypoglycemia, though it may be resumed at lower doses once the hypoglycemia resolves. Patients with hypersensitivity to other insulin products may try insulin aspart with the appropriate support in case of a reaction (antihistamine and/or epinephrine as needed).

Monitoring

Critically ill patients receiving insulin aspart should have their glucose monitored every 1 to 2 hours. Non-critically ill patients using insulin aspart should monitor their blood glucose concentration routinely at home or in the hospital to assess the efficacy of the insulin dose. Preferably, this should be done either before a meal or 2 hours after a meal. Insulin doses should be adjusted based on the monitored blood glucose concentrations, generally a 105 to 20% adjustment in either direction. All patients on insulin therapy should receive biannual hemoglobin A1c monitoring and annual electrolyte monitoring. Hemoglobin A1c should be monitored quarterly in patients not meeting treatment goals or after changes in therapy.

According to the American Diabetes Association, monitoring goals include fasting blood glucose 80 to 130 mg/dL, peak postprandial (1 to 2 hours after a meal), blood glucose less than 180 mg/dL, and hemoglobin A1c less than less 7.0% for non-pregnant adult patients. Glycemic goals may change for individual patients based on the patient’s age, duration of diabetes mellitus, comorbid conditions, hypoglycemia unawareness, risks of hypoglycemic events, and other individual patient considerations, with less stringent goals for patients with more comorbid conditions or higher risk of harm in a hypoglycemic event.

Toxicity

Toxic effects of insulin aspart include hypoglycemia, which is treated by giving glucose, dextrose, or oral carbohydrates to increase blood glucose concentrations. To treat the hypoglycemic episode, patients who can consume oral carbohydrates, including glucose gel, tablets, or glucose-containing food, should consume 15 grams of carbohydrates. Wait 15 minutes after eating the glucose to recheck blood glucose, and if it remains hypoglycemic, repeat the treatment. Once the glucose returns to normal, the patient should eat a meal within the next hour to prevent the recurrence of hypoglycemia.[10] If the patient is unable or unwilling to consume oral glucose, intramuscular glucagon is used for ambulatory patients, either administered by themselves or a caregiver. Intravenous dextrose can be used in conscious and unconscious hospitalized patients with hypoglycemia, administering 10 to 25 g per dose of IV dextrose. Blood glucose concentration should be monitored 15 minutes after receiving dextrose, and repeat doses of IV dextrose or intramuscular (IM) glucagon may be necessary until blood glucose returns to normal. Additionally, after any hypoglycemic event, insulin doses should be evaluated and adjusted to prevent additional hypoglycemia.[11]

Enhancing Healthcare Team Outcomes

All healthcare professionals, including clinicians, nurses, and pharmacists whose patients use insulin aspart should be familiar with its indications and adverse effects. Insulin aspart is a rapid-acting, human insulin analog that is FDA approved for the treatment of type-1 and type-2 diabetes mellitus to improve glycemic control in adults and children. Insulin aspart may also be used to treat diabetic ketoacidosis (DKA), though this is not an FDA-approved indication. Insulin aspart should be used in addition to a long-acting (basal) insulin for complete therapy unless used in a continuous subcutaneous (insulin pump) or intravenous insulin infusion. All interprofessional healthcare team members need to educate the patient regarding proper dosing and usage of insulin aspart and engage in open communication regarding any potential dosing adjustments to prevent possible hypoglycemia.

Rapid-acting insulin products target controlling post-prandial blood glucose concentrations, or reducing blood glucose in response to an elevated blood glucose measurement, as in a correctional scale. It is crucial for healthcare professionals to monitor glucose concentrations closely when administering insulin aspart as it can induce hypoglycemia. Thus, it is always important to have some type of glucose-containing fluid or a meal ready in case hypoglycemia develops.[12]