Diabetes in Pets

Novolin NPH/isophane insulin.

NPH Insulins, or "Neutral Protamine Hagedorn", now describes the set of insulins using Isophane / Protamine as their suspension. In North America, Humulin N and Novolin N are the most common brands of NPH insulin. Another term for this type of insulin is Isophane; it's commonly used to describe this insulin type outside of North America.

NPH was first launched in 1946 in Denmark by Novo Nordisk as the first longer-lasting neutral pH insulin for human use. "Hagedorn", was the chief scientist who invented it.

The difference between NPH/isophane insulin and PZI insulin is the amount of protamine in the suspension. PZI has more of it and this is what makes it a slow-acting insulin, in contrast to NPH/isophane being an intermediate-acting (or in some cats, short-acting) one[1], as the additional protamine extends the duration.

Specifications of NPH/isophane insulin

letin II NPH--pork isophane insulin--Canadian packaging.

British National Formulary[2]defines this type as: A sterile suspension bovine or porcine or of human insulin in the form of a complex obtained by the addition of protamine sulphate or another suitable protamine.

British Pharmacoepia and United States Pharmacopia definitions:[3]

Isophane Insulin

Sterile buffered suspension of insulin in the form of a complex obtained by addition of suitable protamine. Prepared from crystalline insulin. pH 6.9 - 7.5 iso-osmotic with blood. Contains for each 100 units of insulin, 300 - 600 g protamine sulphate and not more than 40 g zinc, a suitable bactericide and sodium phosphate as buffering agent.

USP specification: Sterile suspension of zinc insulin crystalline and protamine sulphate in buffered water for injection. Solid phase contain crystals of insulin protamine and zinc; 40, 80, 100 units/ml. Contains glycerol, metacresol, phenol sodium phosphate and zinc.

Additional details

Human time activity profile for r-DNA/GE/GM NPH/isophane insulin.

NPH is the most widely used type of insulin for treatment of diabetic dogs, but is shorter-acting and less predictable in cats[4][5][6]. With a peak of 1.5-6 hours and duration of 4-10 hours, if it is successfully used, twice-daily dosing is a must[7]. See also Humulin N 101 for Cats at link below[8].

This 1987 study[9] of direct comparisons between R and NPH insulins in dogs, found R insulin to be absorbed better than NPH and suggests that NPH insulin may have an earlier peak and shorter duration than previously thought.

Novo Nordisk's and Lilly's analog insulin mixes NovoLog and Humalog employ protamine/isophane suspension; non-mix Novolog and Humalog do not.

NPH/isophane insulins

The following commercial insulins are all generically NPH insulins:

NPH/Isophane Insulins

All Intermediate acting


Hypurin Bovine Isophane


Iletin I NPH
(No longer produced.)


Hypurin Porcine Isophane
Hypurin Pork NPH


Pork Insulatard


Iletin II NPH
(No longer produced.)


Humulin N, Humulin I


Insuman Basal


Novolin N, Insulatard
ReliOn/Novolin NPH, Protaphane

Other commonly used names are:

  • NPH insulin, NPH
  • isophane insulin

Further Reading