by 
What is Insulin Lispro?
The rapid-acting insulin analog Insulin Lispro was one of the first rapid-acting insulin to be developed. Insulin Lispro is a synthetic version of human insulin that has been genetically altered. The slight alteration in the amino acid sequence results in Lispro being absorbed faster after injection under the skin as compared to regular human insulin.
Chemical Structure and Mechanism of Action
Like natural human insulin, Insulin Lispro is composed of 51 amino acids arranged in two chains called the A-chain and B-chain which are connected by disulfide bonds. However, the lysine and proline amino acids at position B28 are reversed in Lispro. This small change allows Lispro to self-associate more slowly after injection, resulting in a faster absorption and onset of action. Once injected, Lispro binds to insulin receptors on fat, liver and muscle cells to facilitate glucose entry into these cells and reduce blood glucose levels.
Indications and Usage
Insulin Lispro is predominantly used in Type 1 diabetes and sometimes in Type 2 diabetes as well where rapid-acting coverage is needed to handle post-meal blood glucose excursions. It is commonly used in ambulatory insulin regimens involving pre-meal insulin administration. Lispro helps control post-prandial hyperglycemia by providing faster action to match prandial insulin need compared to regular human insulin. It provides glycemic control when administered 15 minutes before or right at the start of meals.
Pharmacokinetic Properties
Clinical studies have shown that Insulin Lispro has a faster absorption and action profile compared to regular human insulin. Its time of onset is approximately 15 minutes compared to 30-60 minutes for regular insulin. Peak blood levels and action occur at 60 minutes on average compared to 90-120 minutes for regular insulin. Its overall duration of action is 4 hours as compared to 6-8 hours for regular insulin. This allows Lispro to more closely mimic the body’s natural endogenous prandial insulin secretions triggered by meals.
Advantages over Regular Human Insulin
– Faster onset of action within 15 minutes provides improved post-prandial glycemic control compared to 30-60 minutes for regular insulin.
– Earlier peak action at 60 minutes vs 90-120 minutes matches insulin requirements after meals more accurately.
– Shorter duration of action of 4 hours reduces risk of late hypoglycemia compared to 6-8 hours for regular insulin.
– More physiological action profile aligns administered insulin with carbohydrate intake at meals for better glycemic management.
– Convenience of administration right before or at the start of meals reduces reliance on timing injections in advance.
Clinical Studies and Efficacy
Numerous clinical studies have demonstrated the efficacy and safety of Insulin Lispro in type 1 and type 2 diabetic patients. In one landmark study, 144 type 1 patients randomized to Lispro or regular human insulin showed superior post-prandial glucose control and less post-meal hyperglycemia with Lispro. HbA1c reductions were comparable between groups. Other studies have found no difference in hypoglycemia risk between Lispro and regular insulin when dosed appropriately before meals. Overall, Insulin Lispro provides effective glycemic management with the advantages of faster absorption and a more physiological profile matching mealtime insulin needs.
Side Effects and Precautions
The safety profile of Insulin Lispro is generally comparable to that of regular human insulin. Common minor side effects may include hypoglycemia if dosages are not lowered during periods of reduced calorie or carbohydrate intake. Lipoatrophy or lipohypertrophy can occur at injection sites due to local breakdown of fat tissue. Allergic reactions are rare. Safety in pregnancy has not been established conclusively but Lispro is usually considered safe to use. Caution is required in patients with renal or hepatic impairment or in cases of illness, stress or change in diet or activity levels as this may impact insulin requirements. As with any insulin therapy, blood glucose monitoring is essential to guide dosing adjustments and avoid hypoglycemia.
Dosage Forms and Administration
Insulin Lispro is supplied as a clear solution in vials or prefilled pens for subcutaneous injection. It works best when injected 15 minutes before or soon after starting a meal. Injection sites should be rotated daily between abdomen, thighs, buttocks and deltoid regions of upper arms.
Conclusion
As one of the first rapid-acting insulin analogs developed, Insulin Lispro revolutionized post-prandial glycemic management in diabetes. Its slightly modified structure allows faster absorption and a more physiological profile matching endogenous insulin secretion after meals. Numerous clinical trials have shown Lispro to provide effective glycemic control with a reduced risk of post-prandial hyperglycemia compared to regular human insulin. For patients needing mealtime insulin coverage, Lispro remains an important therapeutic option with advantages over regular human insulin.
