Canine Diabetes Wiki
FDA Warning Letter to Eli Lilly re: instability of insulin Lispro (Humalog) crystals-10 February 2010
Reuters News story re: Lilly/Humalog Warning Letter-23 February 2010
Insulin hex di mon

Insulin hexamers must break down into dimers and monomers to be absorbed. [1]


Alterations to human insulin structure producing insulins lispro (Humalog) and aspart (NovoRapid/Novolog).

Humalog is an Eli Lilly fast-acting analog insulin also known as insulin lispro. [2] Insulin lispro has been altered from the human insulin molecule at positions #28 and #29 on the B insulin chain. The normal amino acids present at B-#28 and B-#29 are Proline (#B-28) and Lysine (B-#29); insulin lispro reverses this so that Lysine is found at B-#28 and Proline at B-#29. [3]


Human time activity profile for insulins lispro (Humalog) and aspart (Novolog/NovoRapid).

Inverting the normal Proline-Lysine sequence of human insulin at positions #28 & #29 on the B insulin chain created an analog insulin which has less tendency to form into hexamers (self-association). [4] Keeping the insulin from forming hexamers means that in dimer and monomer form, they are able to be absorbed faster and that means more rapid onset, peak and less duration.

Insulin lispro has been known to "wilt" easily when not constantly refrigerated. Those who have had bad vials report finding hazy or small particles on inspection. [5] Humalog degrades rapidly--it can be working well one day but not the next. [6]

Dr. Nelson of University of California-Davis said in his lecture at the Ohio State Endocrinology Symposium in 2006 that if the short-acting analog insulins have any role in feline and canine diabetes, it is not yet determined. [7]

A study of dogs from 1993-1994 using various fractions of Humalog mixes against human NPH/isophane insulin found only minor differences in the use of Humalog Mix as opposed to NPH/isophane insulin. [8] A 2009 study comparing Humalog (insulin lispro) to R insulin when used to treat canine ketoacidosis cases found this analog insulin to be safe and effective. [9]

Analog insulins: amino acid sequence[]

Analog insulins: pharmacokinetics[]

These are human activity profiles.


  1. Hanas, Ragnar (1999). Insulin Dependent Diabetes-page 5. Children With Diabetes.
  2. Humalog-Insulin Lispro.
  3. Alterations to Human Insulin Producing Insulins Lispro, Aspart & Glargine.
  4. Scientific Discussion-Insulin Lispro-Humalog-Page 1. EMEA.
  5. Humalog and Heat.
  6. Humalog & Novolog.
  7. Nelson, Richard (2006). Selecting an Insulin for Treating Diabetes Mellitus in Dogs & Cats-page 39. OSU Endocrinology Symposium.
  8. Humalog Pharmacology Review-Pages 5 & 6. US Food and Drug Administration.
  9. Sears, KW., Drobatz, KJ., Hess, RS. (2009). Use of Lispro Insulin for Treatment of Dogs With Diabetic Ketoacidosis-Abstract #40, page 696. ACVIM.
  10. 10.0 10.1 Guide to Insulin Preparations. Pharmacy Times.
  11. 11.0 11.1 Insulin Pharmacology. Cite error: Invalid <ref> tag; name "Endotext" defined multiple times with different content
  12. Hypurin Protamine Zinc.

More Information[]