What is Lispro (Humalog, insulin lispro)?

From the Guidelines

Lispro is a recommended rapid-acting insulin analog for managing blood glucose levels in people with diabetes, particularly for those who require flexible mealtime dosing. According to the 2017 American Diabetes Association standards of medical care in diabetes 1, lispro can be used as an add-on therapy to basal insulin, with a typical starting dose of 4 U per meal or 0.1 U/kg per meal. The pharmacodynamic profile of lispro allows for convenient mealtime dosing, with a rapid onset of action within 15 minutes after injection, peaking in about 1 hour, and continuing to work for 2-4 hours 1.

Key Considerations for Lispro Use

• Lispro should be injected subcutaneously in the abdomen, thigh, or upper arm immediately before meals
• Dosing must be individualized based on blood glucose monitoring
• Common side effects include hypoglycemia, injection site reactions, and lipodystrophy
• Patients should rotate injection sites and monitor blood glucose regularly, especially when starting treatment or adjusting doses

Treatment Intensification Options

• Adding a single injection of rapid-acting insulin analogue (lispro, aspart, or glulisine) before the largest meal
• Adding a GLP-1–receptor agonist
• Stopping basal insulin and starting twice-daily premixed (or biphasic) insulin
• Using once- or twice-daily 70/30 degludec/aspart mix taken before meals 1

Regimen Flexibility

• Rapid-acting insulin offers greater flexibility in meal planning than premixed insulin
• Providers can consider regimen flexibility when devising a plan for the initiation and adjustment of insulin therapy for patients with type 2 diabetes 1

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Characteristics of Lispro

• Insulin lispro is a rapid-acting insulin analog with a faster onset of action and shorter duration of activity compared to regular human insulin 2, 3
• It has a more rapid absorption due to the inversion of the proline-lysine amino acid sequence at positions 28 and 29 on the B chain 2
• Lispro provides equivalent or slightly improved glycemic control in patients with types I and II diabetes mellitus compared to regular insulin, without subsequent increases in hypoglycemic episodes 2

Clinical Use of Lispro

• Insulin lispro can be administered immediately before or after meals, allowing for greater flexibility in dosing and mealtime scheduling 3
• It is indicated for the treatment of hyperglycemia in diabetes mellitus in many countries worldwide, alone or as a premixture with the longer-acting insulin neutral protamine lispro 3
• Lispro has demonstrated postprandial blood glucose control similar to or better than that achieved with regular human insulin, without an increased risk of hypoglycemia 3, 4

Recent Developments and Potential Clinical Implications

• Recent reformulations of lispro have generated a second generation of more rapid-acting insulin analogue candidates, including ultra-rapid lispro and BioChaperone Lispro 5
• These modifications have the potential to mimic physiological prandial insulin secretion better, with an even earlier onset of action, improved postprandial glucose control, shorter duration of effect, and reduced risk of hypoglycemia 5
• Phase 3 trials in type 1 and type 2 diabetes have shown that ultra-rapid lispro achieves fewer postprandial glucose excursions with a small increase in post-meal hypoglycemia, but similar or marginally superior glycated hemoglobin levels 5

Optimization of Lispro Dosing

• The optimal time for bolus insulin injection was 20 min before the meal for regular insulin and immediately before the meal for lispro 4
• Postprandial injection of lispro did not compromise postprandial blood glucose control and resulted in less hypoglycemia 4
• Reducing the evening premeal lispro dose by 20% and increasing the bedtime basal NPH dose by 25% can improve evening and nighttime glycemic control without deteriorated nighttime glucose levels 6