Canine Diabetes Wiki
Milestone bottle

Close-up of Iletin vial-1923. The insulin was all beef, came in varying strengths and was not highly purified.

Regular, Normal, Neutral, Toronto or Toronto insulin. [1] Toronto is a term used most often in Canada; Toronto is simply another name for R, Normal, or Neutral insulin, no matter who makes it or its origin. Toronto was where Frederick Banting and Charles Best did their work discovering insulin, and terming such insulin Toronto insulin honors their work there.


Human activity profile for r-DNA/GE/GM R (Regular)/Neutral insulin. See links for dog activity.

A short-acting, soluble, non-suspended insulin produced from r-DNA/GE/GM, bovine, or porcine sources. R or neutral insulin is basically zinc insulin crystals dissolved in clear fluid with nothing added to alter its action or speed. [2] From 1921 to the 1930's when PZI was developed, R was the only kind of insulin available. [3]

While both R/neutral and semilente insulins are considered fast-acting, they differ in a few ways. As above, there's no suspension or buffer [4] in R/neutral; it's totally dissolved and soluble, meaning it can safely be used intravenously. [5] R/neutral is clear and does not need to be resuspended before using.

The very small insulin particles in semilente insulin are suspended by zinc. [4]. Semilente is cloudy, has an acetate buffer and cannot be used intravenously. Semilente also needs resuspending before being used.

R/Neutral insulin cannot be reliably mixed with Lente or Ultralente insulins. [6][7] Semilente can; the ratio of 3 parts semilente insulin to 7 parts ultralente insulin produces Lente insulin. [4]

Toronto insulin ca 1930

Toronto insulin circa 1930's.

R/Neutral Insulins[]


  1. Definition of Neutral Insulin-Should Say "Mammalian". InChem.
  2. Humulin R. Eli Lilly.
  3. Chase, Lillian A. (1938). Some Rules for Dosage of Protamine Zinc Insulin. Canadian Medical Journal.
  4. 4.0 4.1 4.2 DeRuiter, Jack. Insulin Preparations-Regular Insulin. Auburn University. Cite error: Invalid <ref> tag; name "Auburn" defined multiple times with different content Cite error: Invalid <ref> tag; name "Auburn" defined multiple times with different content
  5. Maddison, Jill E.,Page, Stephen W.,Church, David B. (2008). Small Animal Clinical Pharmacology. Saunders Ltd..
  6. Deckert, T. (1980). Intermediate-Acting Insulin Preparations: NPH (Isophane) & Lente. Diabetes Care.
    Note--in 1980, there was only beef Lente-type insulin--no pork or r-DNA/GE/GMLente insulins
  7. Resource Guide. American Diabetes Association (2005).

More Information[]