Rapid-Acting Insulins

Lispro (brand name: Humalog) is the rapid-acting insulin currently used on the inpatient Stead Family Children’s Hospital formulary.

Humalog is a synthetic form of human insulin modified at positions 28 (Lysine to Proline) and 29 (Proline to Lysine) in the B-chain as seen in Figure 1.

Figure 1 – Structure of insulin lispro. Ala alanine, Arg arginine, Asn asparagine, Cys cysteine, Gln glutamine, Glu glutamic acid, Gly glycine, His histidine, Ile isoleucine, Leu leucine, Lys lysine, Phe phenylalanine, Pro proline, Ser serine, Thr threonine, Tyr tyrosine, Val valine. Image Attribution: “Structure of insulin lispro” by Candido at al, 2018 CC BY-NC 4.0

While these substitutions appear minor, they cause a significant increase in the absorption rate of this analog insulin into the blood after subcutaneous injection (or infusion) compared to Regular insulin (short-acting) insulin.

This increased absorption rate accounts for the quicker onset of action (10-15 minutes), leading to early peak action (by 1 hour) and a shorter duration of action (cleared from the system by 2 to 4 hours after injection).

Rapid-acting insulin is now the most common type of insulin utilized in basal/bolus regimens for subcutaneous injection and subcutaneous infusion.

Administration:

Rapid-acting insulin boluses are ideally given 15 minutes BEFORE anticipated meals, as this is how long it takes for the insulin to move from the subcutaneous space into the bloodstream and start having action at its insulin receptors.

Figure 2 – Rapid-acting insulin is best dosed 15 minutes (or sometimes sooner) before a carbohydrate-containing meal.

Coincidentally, this is also about how long the initial carbohydrates are absorbed from ingested food at a meal.

This paired timing of insulin action with ingestion of food allows for ideal post-prandial blood glucose in the target range, as discussed in Figure 3.

Figure 3 – “Ideal postprandial blood glucose levels = right insulin dose + right injection time. Ideal postprandial BG control requires an appropriate dose of insulin given at the right time so that the rate of BG appearance after a meal is matched by the rate of BG disappearance. If the insulin dose is too low, the glucose disappearance rate will not match the rate of glucose appearance, resulting in postprandial hyperglycemia. If the insulin dose is administered too late, the rate of BG disappearance will also not match the rate of BG appearance, resulting in postprandial hyperglycemia and late postprandial hypoglycemia. Patient education often focuses on postprandial BG levels and assumes that high BG levels are due to the insulin doses being too low, but they may also reflect that insulin action is too late. Horizontal dashed lines represent the glycemic target range. BG, blood glucose.” Image Attribution: by Senior and Hramiak (2019) CC BY-NC-ND 4.0

For young or very sick children who are unpredictable eaters, rapid-acting insulin can be given right after allowing 20-30 minutes to eat the carb-containing foods that they are able to eat. The delivered dose of insulin is determined by the amount of ingested carbohydrates eaten during the 20-30 minutes timeframe. This is not ideal and often leads to more significant post-prandial blood glucose spikes and more difficulties getting post-prandial blood glucose to remain in the target range.

Rapid-acting insulin is the only type of insulin used in insulin pumps. The continuous low rate of rapid-acting insulin infusion via a pump replaces the need for a subcutaneous injectable long-acting insulin. Boluses for carbohydrate coverage should still be given at least 15 minutes before eating.

Many different brands of rapid-acting insulin used in the outpatient setting are unavailable on the inpatient formulary. These include:

  • Lispro (Admelog, Lyumjev),
  • Apidra (Glulisine)
  • Aspart (Novolog, Fiasp)
    • Fiasp is an ultra-rapid-acting insulin with a quicker onset of action of 5-10 minutes compared to Novolog and the other rapid-acting insulins listed here.

Conversion from one rapid-acting insulin to another rapid-acting insulin is a 1:1 conversion and, therefore, does not require any specific dose adjustment.

Quiz Yourself:

Bibliography:

  1. Candido R, Wyne K, Romoli E. A Review of Basal-Bolus Therapy Using Insulin Glargine and Insulin Lispro in the Management of Diabetes Mellitus. Diabetes Ther. 2018 Jun;9(3):927-949. doi: 10.1007/s13300-018-0422-4. Epub 2018 Apr 13. PMID: 29654514; PMCID: PMC5984925.
  2. Senior P, Hramiak I. Fast-Acting Insulin Aspart and the Need for New Mealtime Insulin Analogues in Adults With Type 1 and Type 2 Diabetes: A Canadian Perspective. Can J Diabetes. 2019 Oct;43(7):515-523. doi: 10.1016/j.jcjd.2019.01.004. Epub 2019 Jan 24. PMID: 30872107.

Figures:

Figure 2: Image Attribution: Created by Alex Tuttle by compilation of the following images from left to right: “Insulin icons” by vectorsmarket15, “15 minutes icon” by Freepik, and “Eat icons” by Eucalyp from Flaticon.com

 

 

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