Insulin is a small peptide hormone that has a highly conserved amino acid sequence throughout different mammalian species. This allows for the use of human- based insulins in veterinary species. Insulin is secreted in a stable hexameric form stabilized by a zinc molecule in the middle. The hexamer needs to be broken down to a monomer before it can bind to the insulin receptor and activate cells. In considering insulin therapy, the practitioner should be aware of the source of the insulin (animal, human recombinant DNA, human sequence mutated), the type of the insulin or how it is made into a repository form, and the concentration (U-40, U-100, U-300).

Regular insulin is available as a human recombinant insulin in 100 U/ml (U-100) form. It is the stabilized hexameric form of insulin, and therefore, not precipitated or mutated. It may be used intravenously, intramuscularly, and subcutaneously. Regular insulin is used to treat unstable or dehydrated diabetics. Effective protocols for IM intermittent therapy or continuous rate IV infusion are available in any emergency medicine handbook.

Protamine Zinc Insulin (ProZinc^®) is human recombinant insulin. It is precipitated with protamine zinc and is stable in suspension. It should be rolled gently to mix. ProZinc^® is formulated at a concentration of 40 U/ml; therefore dosing can be easier in smaller animals like cats. The 0.3 ml syringes can be used so that half units can be easily measured. ProZinc^® is approved by the FDA for veterinary use; therefore, company support of the product is readily available for veterinarians. This is a great insulin in cats and also is effective in dogs.

Vetsulin^® is a purified porcine insulin that has an identical amino acid sequence to canine insulin. It is a mixture of ultralente and semilente insulins and is precipitated with zinc to form a suspension. To keep the ratio of semilente to ultralente consistent, it must be shaken vigorously before use. VetPens^® containing Vetsulin^® are available for convenient dosing by owners. These pens may be measured for accurate ½ unit dosing. Vetsulin^® is approved for veterinary use by the FDA and company support is readily available for veterinarians. This should be a first pick for dogs and is also effective in cats.

NPH (neutral protamine hagedorn) is a recombinant human insulin. It is distributed by several manufacturers under names such as Humulin N® (Eli Lilly) and Novolin N® (Novo Nordisk). A generic version is also available. It is a crystalline suspension of human recombinant insulin with protamine and zinc added. The concentration of NPH is 100 U/ml. This is the most inexpensive insulin on the market and may work in some dogs. It has a short duration of action in cats that can remain hyperglycemic for significant portions of the day. Thus, NPH is not recommended as a long term insulin in cats (unless the owners want to give 3–4 injections daily to their cat).

Glargine (Lantus ^®) is a long-acting human mutated insulin available as a U-100 and U-300. It is stable at pH 4.0 but forms crystals at pH 7.0 when injected under the skin. Insulin adsorbs off the crystals and is released into the blood stream. It is marketed to give 24 hour basal control of insulin circulation. In humans, glargine is often used in a basal-bolus pattern with injection of another insulin preparation at meal times. Lantus^® pens are available but are only adjustable in 1U increments and have relatively short injection needles. This is a great insulin in cats and will also work in dogs.

Detemir (Levemir^®) is a similar insulin to glargine in its use in human diabetes mellitus. It is a mutated human insulin with fatty acid side chains added so that it can bind to albumin after being injected under the skin. It is also available as a prefilled pen with the caveats of the Lantus^® pen. This is a fabulous insulin in dogs especially as a “rescue” insulin. It may also be used in cats.

Lispro (Novalog^®) and Aspart (Humalog^®) are two mutated human recombinant insulins that are used to manage human diabetes mellitus along with the longer acting glargine and detemir insulins. They are available as U-100 insulins. These insulins work extremely quickly because they are already in monomeric form and do not need to be broken down from the normal insulin hexamers. Their onset of action is rapid (5–15 minutes) and their duration of action is approximately 1 hour. Their use has been limited in veterinary medicine.

The starting dose of insulin should be: 0.25 U/kg for cats and 0.5 U/kg for dogs, except for detemir in dogs that should be started at a lower dose of 0.25 U/kg. Most dogs and cats will need insulin twice per day. If owners are only able to give insulin once per day, consider Vetsulin^® or Levemir^® in dogs and ProZinc^® or Lantus^® in cats. Dogs and cats should be fed twice a day when insulin is given. A small amount of food should be presented, and the animal’s appetite noted. Insulin should then be given. If the pet does not eat normally, half the dose of insulin should be given. Many owners give insulin while the animal is eating. This makes the insulin injection a pleasant experience for the pets and easier for owners to treat the animal. Some cats prefer to nibble food throughout the day. These grazers can often be well managed by allowing them free choice eating with insulin injections twice per day. Care should be taken to ensure that the cats are not receiving more than their caloric needs since extra weight should be avoided.

Exercise is beneficial to diabetics and serves to lower insulin requirements and provide better glycemic control. Daily walking for dogs and cat play can be effective ancillary treatments for diabetes mellitus. Average time for initial diabetic control is 4–6 weeks.