From the Guidelines
Humalog (insulin lispro) and U-500 (concentrated regular insulin) differ significantly in their concentration, action profiles, and intended use, with Humalog being a rapid-acting insulin analog for mealtime use and U-500 being a highly concentrated insulin for patients with severe insulin resistance requiring large daily doses. The primary distinction between Humalog and U-500 lies in their concentration and pharmacokinetic properties. Humalog, a rapid-acting insulin analog, is typically available in a U-100 concentration, starting to work within 15 minutes, peaking between 30-90 minutes, and lasting 3-5 hours, making it suitable for mealtime use to manage postprandial glucose spikes 1. In contrast, U-500 insulin is a highly concentrated form of regular human insulin, with a concentration of 500 units per mL, which is five times more concentrated than the standard U-100 insulin. U-500 insulin has a unique action profile, with both rapid and extended components, beginning to work within 30 minutes, peaking at 4-8 hours, and lasting up to 24 hours, which makes it suitable for patients with severe insulin resistance who require daily doses exceeding 200 units 1.
Key differences and considerations include:
- Concentration: U-500 is significantly more concentrated than Humalog (U-100).
- Action Profile: Humalog is rapid-acting, while U-500 has a prolonged action with both rapid and extended components.
- Indication: Humalog is used for mealtime glucose control, whereas U-500 is specifically indicated for patients with severe insulin resistance requiring high daily doses of insulin.
- Dosing Considerations: Due to its high concentration, U-500 requires careful dosing and the use of dedicated U-500 syringes or pens to prevent dosing errors.
- Patient Supervision: Patients switching between these insulins need close medical supervision due to their different potencies and action profiles.
Given the most recent evidence from 2024 1, the choice between Humalog and U-500 should be based on the individual patient's insulin needs, with U-500 being reserved for those with severe insulin resistance and high daily insulin requirements, and Humalog being more appropriate for mealtime glucose control in patients without such extensive insulin needs.
From the Research
Key Differences
- Humalog (insulin lispro) is a rapid-acting insulin analog, whereas U-500 is a concentrated form of human regular insulin, five times more concentrated than traditional regular human insulin (U-100) 2.
- U-500 contains 500 units of insulin per milliliter, compared to 100 units per milliliter in most other insulin types, including Humalog 2.
- Humalog is typically used for prandial (meal-time) insulin coverage, while U-500 can be used for both prandial and basal (background) insulin coverage, and can be injected as monotherapy in a twice-daily regimen 2, 3.
Pharmacokinetics and Pharmacodynamics
- Studies have shown that U-500 has a similar overall insulin exposure and effect to U-100 insulin, but with a blunted peak concentration and a prolonged duration of action 4.
- In contrast, ultra rapid lispro (a formulation of insulin lispro) has been shown to have an accelerated absorption and greater postprandial glucose reduction compared to Humalog in patients with type 1 diabetes mellitus 5.
Clinical Use
- U-500 is indicated for patients with type 2 diabetes who require more than 200 units of insulin per day, and has been shown to be effective and safe in this population, with benefits including better compliance and decreased injection pain 2, 3.
- However, U-500 also carries a risk of hypoglycemia and weight gain, and dosing errors can occur due to its high concentration 2.