Rapid Acting Insulin (Fast acting Insulin or Ultra-Short acting Insulin)

Rapid-acting Insulin has a very rapid onset of action, hence it can be administered with meals. It also has low risks of hypoglycemias because of its short duration of action

Insulin is a life-saving drug. All individuals who have Type 1 Diabetes require insulin. Most patients with Type 2 Diabetes also require some form of insulin.

Insulin is especially recommended if the person has developed complications like:

• advanced Kidney Disease,
• heart disease,
• liver disease, and
• patients who are undergoing any surgical procedure.

In type 2 diabetes, there is a progressive loss of beta-cell function and the patient may become insulin deficient.

The beta-cell dysfunction declines over time and it is estimated that 50% of all type 2 diabetic patients required insulin after 8 years of their diabetes. Insulin is produced by the human pancreatic Beta cells.

The onset of action of Human Regular Insulin:

• Human Regular Insulin has an onset of action of about 10 to 30 minutes.

Concentrated forms of human regular insulins have been developed such as the U-500. Concentrated human insulin (U-500) contains five times the units of insulin per one ml compared to U-100 insulin.

• U-500 human Insulin has an onset of action of 10 to 30 minutes when administered intravenously.
• When administered subcutaneously, the U-500 human insulin has an onset of action of about 15 minutes.

The U-100 insulin has an onset of action of about 30 minutes.

Peak effect of Human Regular Insulin:

• The peak effect of human regular insulin U-100 is 1.5 to 3.5 hours when administered subcutaneously and that of U-500 is 4 – 8 hours.

Total duration of Human Regular Insulin:

• The total duration of action of U-100 human regular insulin is 8 hours when administered subcutaneously and that of U-500 is about 13 – 24 hours.

Rapid Acting Insulin (Fast-acting Insulin or Ultra-Short acting Insulin)

Rapid-acting Insulin also called short-acting, faster-acting, or ultra-short-acting insulin [Ref] is usually administered just before a meal to provide insulin coverage for that specific meal.

It has the convenience of being available as a pen, carried in pockets (provided the temperature is maintained), and has less waiting time before the meal can be taken.

Rapid-acting Insulin (faster-acting insulins) include:

• Insulin Aspart and Faster Aspart
• Insulin Glulisine
• Insulin Lispro and Insulin Lispro AABC
• Inhaled Ultra-short-acting Insulin

Rapid-acting insulins are insulin analogs manufactured by recombinant DNA technology by changing the Amino acid sequence of human insulin.

These Insulins provide pre meals coverage and are considered superior to human regular insulins in patients with Type 1 Diabetes Mellitus.

However, their efficacy in patients with Type 2 Diabetes Mellitus is equivalent to Human Regular Insulin.

Insulin Lispro and Insulin Lispro AABC (Insulin Lyumjev):

Insulin Lispro is prepared by recombinant DNA technology. It differs from human insulin by two amino-acid sequence changes at positions B28 and B29. Lysine and Proline are present at positions B28 and B29 respectively.

• Formulations available:

  • Insulin Humalog and Admelog
  • Insulin Lyumjev (It is slightly different from Insulin Humalog and Admelog as it contains treprostinil and citrate that enhances its absorption through the skin, hence, it has a faster onset of action compared to Insulin Humalog and Admelog)

• The Onset of Action Insulin Lispro:

  • Insulin Humalog and Admelog have an onset of action of about 30 minutes in T1DM and 45 minutes in T2DM.
  • Insulin Lyumjev has an onset of action of 15 to 20 minutes in T1DM and 30 minutes in T2DM.

• The Peak effect of Insulin Lispro:

  • Insulin Admelog: About 2.1 hours.
  • Insulin Humalog: About 2.4 to 2.8 hours.
  • Insulin Lyumjev: About 2 to 2.9 hours.

• The duration of action of Insulin Lispro:

  • Insulin Admelog: About 6.9 hours.
  • Insulin Humalog: 5.7 – 6.6 hours.
  • Insulin Lyumjev: 4.6 – 7.3 hours.

• Bioavailability of Insulin Lispro when administered subQ:

  • Insulin Admelog and Insulin Humalog: 55% to 77%
  • Insulin Lyumjev: 65%.

• Half-life elimination of Insulin Lispro:

  • Insulin Admelog and Insulin Humalog: 51 to 60 minutes;
  • Insulin Lyumjev: 44 minutes.

Insulin Aspart and Faster Aspart (FiAsp):

Insulin Aspart and FiAsp are prepared by recombinant DNA technology. It differs from human insulin by replacing proline in human insulin at position B28 with aspartic acid.

• Formulations available:

  • Insulin Novolog, Insulin Novorapid
  • Insulin FiAsp (Faster Aspart)

• The Onset of Action Insulin Aspart and Faster Aspart:

  • Insulin Novolog and Insulin Novorapid have an onset of action of about 20 – 30 minutes.
  • Insulin FiAsp has an onset of action of 16 minutes in T1DM and 22.4 minutes in T2DM.

• The Peak effect of Insulin Aspart and Faster Aspart:

  • Insulin Novolog and Insulin Novorapid: 1 – 3 hours in T1DM.
  • Insulin FiAsp: About 1.5 – 2.2 hours in T1DM and 2.5 hours in T2DM.

• The duration of action of Insulin Aspart and Faster Aspart:

  • Insulin Novorapid and Insulin Novolog: 3 – 7.2 hours in T1DM
  • Insulin FiAsp: 5 – 7 hours in T1DM.

• Half-life elimination of Insulin Aspart and Faster Aspart:

  • Insulin Novorapid and Insulin Novolog: 81 minutes
  • Insulin FiAsp: 1.1 hours

Insulin Glulisine (Apidra):

Insulin Glulisine is prepared by recombinant DNA technology. It differs from human insulin by two amino-acid sequence changes at positions B3 and B29. Lysine replaces Asparagine at position B3 and glutamic acid replaces lysine at position B29.

• Formulations available:

  • Insulin Apidra and Apidra Solostar

• The Onset of Action Insulin Glulisine:

  • Insulin Glulisine (Apidra) has an onset of action of 20 to 50 minutes.

• The Peak effect of Insulin Glulisine:

  • It has a peak effect in 1.6 – 2.8 hours of administration.

• The duration of action of Insulin Glulisine:

  • It has a duration of action of 3 – 4 hours.

• Bioavailability of Insulin Glulisine when administered subQ:

  • Insulin Glulisine has a bioavailability of about 70%.

• Half-life elimination of Insulin Glulisine:

  • The half-life elimination is 13 minutes when administered intravenously and 42 minutes when administered subQ.

Inhaled Insulin (Insulin Afrezza):

Inhaled Insulin is identical to native human regular insulin, however, it is attached to a carrier molecule that enhances its absorption from the lung surface. It is rapidly absorbed and has a very fast onset of action.

• Formulations available:

  • Inhaler Afrezza via oral inhalation

• The Onset of Action Inhaled Insulin:

  • Inhaled Insulin (Insulin Afrezza) has an onset of action of 12 minutes.

• The Peak effect of Inhaled Insulin (Insulin Afrezza):

  • It has a peak effect in 36 – 55 minutes of inhalation.

• The duration of action of Insulin Afrezza:

  • It has a duration of action of 90 – 270 minutes (1.5 hrs – 4.5 hrs)

• Bioavailability of Inhaled Insulin (Insulin Afrezza):

  • Compared to native human insulin, it has a bioavailability of about 21 – 30%.

• Half-life elimination of Insulin Afrezza:

  • Insulin Afrezza has a half-life elimination is 120 to 206 minutes.

In Summary:

Insulin Afrezza, the inhaled insulin has the rapid onset of action and the shortest duration of action. The onset and duration of action are summarized in the picture below: