Pets with Diabetes: Oral hypoglycemic drugs (glipizide)

Drugs like glipizide (trade name Glucotrol) and glyburide (trade name Micronase or Diabea) can sometimes be used to control hyperglycemia.

Although the exact mechanism of action is not known, it is believed that these drugs work in several ways. Their strongest method of action is to stimulate the beta cells of the pancreas to produce insulin. They also increase the sensitivity of other tissues to insulin, either by causing insulin to bind to the insulin receptor more easily, or by causing the cell to respond more strongly to the insulin, once it is bound to the receptor. These drugs also have other effects on glucose metabolism. But the end result is that blood glucose is lowered. Here's a refresher on basic information about diabetes, insulin, and insulin receptors.

Since their main method of action is to stimulate the pancreas to produce insulin, the pancreas must have functioning beta cells. These drugs will not work for a Type I insulin-dependent diabetic where the pancreas does not produce insulin. Remember, in Type I diabetes the pancreatic beta cells do not produce insulin and Type I diabetes is always insulin dependent (IDDM). In Type II diabetes, there may be decreased responsiveness of the body's cells to insulin, or, the beta cells may be functioning improperly. Type II diabetes may be either insulin dependent (IDDM) or non-insulin dependent (NIDDM)

Dogs versus cats
Because the majority of dogs are Type I insulin-dependent diabetics, oral hypoglycemic drugs are usually ineffective, and usually not even tried as therapy. Some cats are Type I insulin-dependent diabetics and oral hypoglycimic drugs will not work for these cats.

Many cats are Type II diabetics. For those that are non-insulin dependent, the pancreas is producing insulin. It may be that not enough insulin is being produced, or that the normal amount of insulin is being produced but the body's cells are not responding to it properly.

Treatment
There is no definite way to determine if a cat will respond to oral hypoglycemic drugs. When the cat is diagnosed, the vet determines the cat’s overall health, the severity of the diabetes, whether or not the cat has ketoacidosis or other diabetes complications such as hind leg weakness (neuropathy), the cat’s ability to take pills, and the owner’s desires (quick diabetes control, ability to give pills, etc.).

Diabetic cats that are generally healthy and not ketoacidotic are candidates for glipizide therapy. That does not mean they should be started on glipizide, just that it is an option. Cats who have severe symptoms or are ketoacidotic are not candidates for glipizide therapy and are started on insulin therapy.

It is estimated that oral hypoglycemic drugs will work in about 1 of every 8 diabetic cats. Some respond very well to the drugs, while others respond moderately, or not at all. This probably depends on the amount of functioning beta cells that the cat has – and the amount of natural insulin that the pancreas is able to produce. In a cat that has a large number of functioning cells, the oral drugs may be very effective. In a cat that has a small number of functioning cells, the oral drugs may help, but it may not be sufficient to control the hyperglycemia. In a cat with very few functioning beta cells, the oral drugs may be ineffective at controlling hyperglycemia and insulin injections are required.

Adverse reactions to glipizide include hypoglycemia, vomiting shortly after the pill is given, changes In liver enzymes, and jaundice (icterus). Adverse reactions occur in less than 15 percent of cats who are given glipizide. Some possible adverse effects that have been noted in humans include allergic skin reactions and bone marrow suppression. The adverse reactions go away after the drug is no longer given, or sometimes when a lower dose is given. When a cat is on glipizide, the vet should request lab tests to monitor liver function.

Treatment often starts by giving a pill of 2.5 mg twice a day with meals. The cat’s health is examined weekly for the first month including physical exam, body weight, urine glucose and ketone measurements, and bg tests. If there are no adverse effects, the dose can be increased to 5.0 mg twice a day. Therapy continues as long as the cat is stable. The dose can be adjusted depending on the bg values. If the bgs are not controlled within 1 or 2 months of therapy, if the cat’s general health worsens, if adverse reactions occur, if the cat becomes ketoacidotic, or if the owner is dissatisfied with the slow progress, glipizide is discontinued and insulin therapy is begun.

Some cats become resistant to glipizide therapy and insulin is then needed.

For cats who have transient diabetes ("honeymooning"), glipizide may be discontinued and the blood glucose remain normal. This is the same as transient diabetics who receive insulin therapy.

Personal Stories

Brendan is a cat whose diabetes is successfully managed with glipizide and diet.
Hazel and Ginger are two guinea pigs whose diabetes is managed with gliburide.

References
Ettinger and Feldman's Textbook of Veternary Internal Medicine, 1995.
Veterinary Drug Handbook, Second Ed. Plumb. 1995.

	Oral hypoglycemic drugs (glipizide)