Continuing Education Activity

Insulin lispro is an insulin analog that is FDA-approved for the treatment of patients with diabetes mellitus types 1 and 2 to control hyperglycemia. Its off-label uses include treating patients with mild-to-moderate diabetic ketoacidosis, gestational diabetes mellitus, and mild-to-moderate hyperosmolar hyperglycemic state. One unit of insulin lispro is as potent as one unit of human insulin in lowering glucose. This activity describes the mode of action of inhaled corticosteroids, including mechanism of action, pharmacology, adverse event profiles, eligible patient populations, monitoring, and highlights the role of the interprofessional team in the management of conditions where a rapid-acting insulin is beneficial for patient outcomes in diabetes care.

Objectives:

• Explain the mechanism of insulin lispro.
• Summarize the place and purpose of insulin lispro in a glycemic control regimen.
• Review the contraindications and adverse event profile of insulin lispro.
• Identify interprofessional team strategies for improving care coordination and communication to advance insulin lispro and improve outcomes.

Indications

Insulin lispro is an insulin analog that is FDA-approved for the treatment of patients with diabetes mellitus types 1 and 2 to control hyperglycemia. Its off-label uses include treating patients with mild-to-moderate diabetic ketoacidosis, gestational diabetes mellitus, and mild-to-moderate hyperosmolar hyperglycemic state. One unit of insulin lispro is as potent as one unit of human insulin in lowering glucose.[1][2][3][4]

Mechanism of Action

Insulin lispro is a rapid-acting, human insulin analog that works parenterally to lower blood glucose by regulating the metabolism of carbohydrates, proteins, and fats. It works by binding to a glycoprotein receptor specific to insulin on the surface of target cells. These receptors are found on a variety of target tissues, including adipose tissue, skeletal muscle, and the liver.[5][6]

• In adipose tissue, insulin produces free fatty acids by supporting the processing of circulating lipoproteins. This also helps with the synthesis of triglycerides, as well as adipocyte storage. Insulin also directly inhibits the hydrolysis of triglycerides.
• In the liver, insulin stimulates the synthesis of hepatic glycogen and promotes the synthesis of fatty acids.
• In skeletal muscle, insulin works to increase the synthesis of protein and glycogen.

Insulin prompts the cellular uptake of amino acids and increases cellular permeability to a variety of ions. Lastly, insulin can movie potassium intracellularly by activating sodium-potassium ATPase.

The drug itself is synthesized by using a special non-pathogenic laboratory strain of the bacteria Escherichia coli which has been genetically altered by adding the gene for insulin lispro. Human insulin, normally secreted by the pancreas, has the amino acids lysine and proline at positions B28 and B29. Insulin lispro has these amino acids in the reverse positions, with proline at position B28 and lysine at position B29.

Administration

Insulin lispro is available in 100 units/mL and 200 units/mL concentrations. It can be administered subcutaneously (as an injection or as a continuous infusion), or intravenously (IV).[7]

Patients administer subcutaneous injections 15 minutes before or immediately after a meal into areas with fatty tissue, such as the thighs, arms, buttocks, and abdomen. Care is necessary to avoid administering insulin into muscle. The rotation of sites is a recommendation to avoid lipodystrophy. Subcutaneous injections can be given using a syringe or a prefilled pen with either the 100 units/mL or 200 units/mL concentrations. These prefilled pens can deliver insulin in 0.5 to 1 unit increments.

With a continuous subcutaneous insulin infusion, only the 100 units/mL concentration are an option. Patients require proper training in how to utilize the external insulin pump. Infusion sets and insertion sites should be changed every three days, again taking care to rotate infusion sites. The insulin reservoir in the pump should be changed at least every seven days. 

IV administration requires very close medical supervision to ensure the patient does not become hypoglycemic or hypokalemic. One must also be mindful that insulin readily adsorbs into IV tubing and infusion bags; therefore, the exact amount of insulin administered can be significantly less than the apparent amount. The rate of infusion must be adjusted based on the actual effect on the patient's glucose, not on the expected effect based on the dose. 

In general, insulin lispro can be diluted with a sterile diluent but should not be mixed or diluted with any other insulin. However, the one exception is insulin lispro 100 units/mL can be mixed from a vial only with insulin NPH, taking care to draw insulin lispro into the syringe first. This injection must be administered immediately after mixing. Mixing insulin lispro with NHP when contained in an external insulin pump is not an option.

Insulin lispro is safe to use in the pediatric population, but a sterile diluent may be needed.

Adverse Effects

The most common adverse effect found in patients using insulin lispro is hypoglycemia. For this reason, the recommendation is to perform close glucose monitoring for all patients with diabetes, and any changes made to the dosing should be done so under medical supervision. In particular, care is a must with the administration of this drug for patients who are fasting or made to have nothing by mouth for medical reasons. Hypokalemia is another adverse effect to pay close attention to, especially with patients who are using potassium-lowering drugs or taking drugs sensitive to serum potassium level. Other adverse effects include hypertrophy at the injection site, injection site reaction, and lipodystrophy at the injection site.[8][9]

Contraindications

Insulin lispro is contraindicated in patients experiencing hypoglycemia and those who are sensitive to insulin lispro or one of the inactive substances utilized to create the drug.

Insulin lispro is a pregnancy category B drug, meaning animal reproduction studies have not shown risk to the fetus. Nevertheless, there are no well-controlled studies on pregnant women. Per the FDA, this drug should only be used during pregnancy when clearly indicated.

Insulin lispro is not contraindicated in nursing mothers; however, nursing mothers on insulin lispro may need a dose adjustment while lactating.

Monitoring

The therapeutic response to insulin lispro should be monitored by periodic blood glucose testing through the day with a glucometer or by obtaining serum glucose. Glycosylated hemoglobin should be obtained to measure long-term glycemic control on a quarterly to bi-annual basis depending on whether or not patients have stable glycemic control and are meeting their treatment goals.

Toxicity

Intentional or accidental administration of excessive insulin lispro outside of the body's needs will result in hypoglycemia.

Mild to moderate hypoglycemia is evidenced by a blood glucose level less than 70 with or without the following symptoms: irritability, tachycardia, shakiness, lightheadedness or dizziness, anxiety or nervousness, double or blurred vision, mild confusion, sweating, and clamminess. Mild to moderate hypoglycemia can be treated with oral intake of 15 grams of carbohydrate, such as 4 ounces of fruit juice, 8 ounces of milk, or a piece of hard candy. Symptoms should improve within 15 minutes, but if they do not and blood glucose is still less than 70, another 15 grams of carbohydrate should be taken. This cycle of eating 15 grams of carbohydrate, waiting 15 minutes, and then reassessing symptoms and blood glucose level can be repeated approximately three times before the patient should seek medical attention. 

Severe hypoglycemia is evidenced by more serious symptoms including concentration problems, seizures, unconsciousness, and even death. Patients with severe hypoglycemia require administration of glucagon, which is the principal rapid-acting counterregulatory hormone that functions to raise the concentration of glucose in the bloodstream. Patients on insulin should have a glucagon kit prescribed by their physician. The pediatric dosage is 0.02 to 0.03 mg/kg per dose for patients weighing less than 20 kilograms. The dose can be administered every 15 minutes as needed. For pediatric patients greater than 20 kilograms and adults, the dosage is 1 milligram, and can also be administered every 15 minutes as needed. If a patient requires glucagon, they should be taken to a medical facility without delay. If they fail to respond to glucagon, IV dextrose should be started immediately.

Enhancing Healthcare Team Outcomes

Insulin lispro is frequently prescribed by nurse practitioners, primary caregivers, internists, endocrinologists, and many other healthcare workers to manage hyperglycemia. It is vital that anyone who prescribes this insulin, understand that it can rapidly cause hypoglycemia. Thus, monitoring of blood glucose levels is critical. The most common adverse effect found in patients using insulin lispro is hypoglycemia. For this reason, close glucose monitoring is recommended for all patients with diabetes, and any changes made to the dosing should be done so under medical supervision. Hypokalemia is another adverse effect to pay close attention to, especially with patients who are using potassium-lowering drugs or taking drugs sensitive to serum potassium level. Other adverse effects include hypertrophy at the injection site, injection site reaction, and lipodystrophy at the injection site.