Abbreviations: BG, blood glucose; NPH, Neutral Protamine Hagedorn; PZI, protamine zinc insulin; U, units.

Additional Information on Available Insulin Products:

1. Lente (U-40 porcine insulin zinc suspension; Vetsulin, Merck Animal Health) is an intermediate-acting insulin commonly used by the Task Force in dogs. It is FDA approved for use in dogs and cats. It has a close to 12 hr duration of action in most dogs and is useful for minimizing postprandial hyperglycemia.
   
   
2. Glargine (U-100 human recombinant; Lantus, Sanofi) is a longer-acting insulin commonly used by the Task Force in cats because it has an adequate duration of action in most diabetic cats. Several studies have demonstrated that glargine is effective for controlling blood sugar levels in diabetic cats and achieving high remission rates.¹² Glargine can also be used in dogs. It is a human analog insulin with modifications that provide variable solubility at different pHs. Glargine is soluble at a pH of 4.0, the pH at which it is supplied and stored, but in the neutral pH of the body’s blood or subcutaneous tissues it forms microprecipitates, facilitating slow absorption after injection. This results in rapid onset and long duration of action. Glargine is sometimes described as a “peakless” insulin, although peakless does not mean an absence of a nadir in cats but rather refers to glucose utilization rates.⁴ In dogs, a flat blood glucose curve (BGC) may be seen, so glargine can be referred to as a peakless insulin in that species.¹³
   
   
3. PZI (U-40 human recombinant protamine zinc insulin; ProZinc, Boehringer Ingelheim Animal Health) is considered by clinicians as a long-acting insulin, and is FDA approved for use in cats and dogs. In field studies in cats, mean time of the BG nadir was between 5 and 7 hr and the duration of action was 8–24 hr, which was deemed an appropriate duration of action by the FDA.¹⁴ The results suggested that ProZinc should be administered twice daily in most diabetic cats to maintain control of glycemia.¹⁴ This insulin is used in both cats and dogs, although it is less commonly used in dogs. Protamine zinc insulin can have a prolonged duration of action in dogs and may be tried on once-daily dosing schedule to minimize the chances of clinically significant hypoglycemia and/or the Somogyi phenomenon.¹⁵
   
   
4. NPH (U-100 human recombinant; Neutral Protamine Hagedorn Humulin N, Lilly or Novulin N, Novo Nordisk) is an intermediate-acting insulin that is used in dogs. The Task Force does not recommend use of this insulin in cats due to its short duration of action. The duration of action of NPH in dogs is often <12 hr. Some dogs can have postprandial hyperglycemia when treated with this insulin.¹⁶ A combination form of NPH plus regular insulin (70 NPH/30 Regular) is available that may be suitable if the dog has an appropriate duration of action (8–12 hr) with an early nadir or postprandial BG spike. Some clinicians use this product in dogs who develop postprandial hyperglycemia when being treated with NPH.
   
   
5. Detemir (U-100 human recombinant; Levemir, Novo Nordisk) is a long-acting insulin that can be used in both dogs and cats. Detemir is a human analog insulin engineered with modifications that allow it to bind albumin with high affinity in the subcutaneous and intravascular spaces, prolonging the insulin’s absorption.^4,17 This prolonged absorption gives detemir a long and steady duration of action and less variability in biological activity.⁴ Detemir has a very similar profile to glargine (Lantus) in cats in terms of BG control and remission rates.¹² However, cats receiving detemir require a lower median maximal dose than cats receiving glargine (1.75 U per cat for detemir versus 2.5 U per cat of glargine).¹⁸ Dogs are very sensitive to the higher potency of this insulin and require lower starting doses (0.1 U/kg).¹⁹ Particular caution must be used in small dogs because they are more likely to have more frequent hypoglycemic excursions.¹⁹
   
   

Insulin dosages should be based on the patient’s estimated ideal body weight. Judicious initial dosing is recommended because dietary change may alter food intake and affect the therapeutic response to insulin.

Insulin dosages should not be increased more often than q 1–2 wk.

The Task Force recognizes that clients are often cost-constrained. However, choosing a less efficacious insulin can result in higher total costs and careful monitoring. In addition, comparing per-U costs of insulin is more useful than comparing cost per vial. The cost per U of insulin gives a more accurate assessment of the overall cost of using the insulin versus cost per vial.

It should be noted that product pharmacokinetics vary depending on insulin type, product formulation, and the individual patient’s response.

One should employ reasonable dosing flexibility based on individual patient response and the owner’s compliance limitations. For example, a 12± 2-hour window on each side of the dosing interval and occasional missed doses are considered acceptable by most practitioners.

Other insulin types and other therapeutics can be used in dogs and cats based on the patient’s response to first-line insulin therapy and associated recommendations, as discussed in the “Monitoring” section of the guidelines.

Although none of the insulin products available for use in dogs and cats have canine- or feline-specific amino acid sequences, anti-insulin antibodies do not appear to cause a significant clinical problem.

Insulin manufacturers generally recommend discarding opened and used bottles of insulin after 4–6 wk or until the date of expiration listed by the manufacturer. However, if handled carefully and stored in the refrigerator, the Task Force is comfortable using insulins beyond the date of expiration (up to 3–6 mo) as long as they are not discolored, flocculent, or have any change in consistency. Insulin must be discarded if these changes occur. If a lack of BG regulation is noted 3–6 mo after using a specific bottle of insulin, it may be prudent to replace the bottle prior to increasing insulin dose.

Note: When selecting products, veterinarians have a choice among those formulated for humans and those developed and approved by veterinary use. Manufacturers of veterinary-specific products spend resources to have their products reviewed and approved by the FDA for canine or feline use. These products are specifically designed and formulated for dogs and cats and have benefits for their use; they are not human generic products. AAHA suggests that veterinary professionals make every effort to use veterinary FDA-approved products and base their inventory-purchasing decisions on what product is most beneficial to the patient.