Controlling Diabetes Mellitus without Insulin (Spoiler: It Only Works in Special Situations)

In people, diabetes is readily classified into Type I and Type II forms. A Type I human diabetic cannot produce insulin whatsoever and is totally dependent on insulin injections. The Type II diabetic develops diabetes later in life and simply has an inadequate (i.e. only partial) ability for insulin secretion. Since insulin injections are unpopular among people, there is a demand for oral products to control blood sugar. Unfortunately, there is just no substitute for insulin when you need it. That said, there are ways to improve insulin secretion where there is potential to do so, plus we may be able to make what little insulin there is work better.

Insulin injections are not only unpopular with people receiving them; they are also unpopular with people administering them to their pets. Dogs, like Type I human diabetics, are universally insulin-dependent, and oral products have been a crashing failure in this species, with the exception of acarbose (see below). In cats, there is a more positive outlook, though insulin is necessary for most patients. We will summarize what is available.

Oral Agents for Cats

It seems that, in general, cats experience diabetes that is analogous to human Type II diabetes mellitus; that is, these cats are still able to produce at least some insulin. Many feline patients (up to 30%) are able to experience diabetic regulation using oral medications alone; however, there is no way to identify these patients without trying medication and seeing if it works. 

Bexagliflozin (Bexacat®)

Bexagliflozin is what is called an SGLT2 inhibitor. What that means is that SGLT2 would normally be responsible for reabsorbing glucose out of the urine. In healthy bodies, glucose is an important fuel, and we don't want to be frivolously losing it in the toilet or litter box so SGLT2 sees that about 97% of that glucose stays in the body. When we inhibit SGLT2, all that glucose gets dumped. Diabetics have huge amounts of circulating glucose and need it dumped, so this is a good thing. Bexagliflozin is a once daily pill used in cats instead of insulin. 

Not every diabetic cat can take bexagliflozin; in fact, it is only an option for cats who have never been treated with insulin, have no concurrent pancreatitis, and can be monitored with regular observation and testing. Further, many circumstances can arise, necessitating changing therapy over to insulin injections. For details on this medication, click here.

Glipizide (Glucotrol®)
Glipizide acts by maximizing the ability of the pancreas to make and secrete insulin. For some patients, this is all it takes to achieve diabetic control. There is some capacity for side effects (15% of cats taking this medication will get an upset stomach), plus most cats will not be controlled with this medication alone. Glipizide is generally considered to be a last resort (i.e., when it is absolutely not possible to give insulin injections). The reason glipizide is not a first-choice medication involves the way it works on the pancreas. Glipizide's process of maximizing insulin production also maximizes the production of an abnormal protein called amyloid, leading to an amyloid buildup in the pancreas. Most cats became diabetic in the first place by having excessive amounts of amyloid in the pancreas, so making more potentially leads to the progression of diabetes in the long run.

At this time, bexagliflozin and glipizide are the only oral medications that could provide an alternative to insulin injections under the right circumstances.

Other oral products reviewed below are meant as supplements to insulin injections. 

Metformin (Diabex®, Glucophage®, Diaformin®)
This medication acts by increasing tissue sensitivity to insulin (i.e., it makes insulin stronger). Unlike glipizide, metformin cannot cause blood sugar to drop too low but lethargy, vomiting, and appetite loss have been reported as side effects in cats. It cannot safely be used in cats with kidney insufficiency, with ketoacidosis or any other form of acidosis, or in cats where an iodine-containing radiographic contrast agent is going to be used in the next few days. Since ketoacidosis can come up unexpectedly in a diabetic pet, this product may not be a good choice. Feline studies are in progress but look promising for cats as a supplement to insulin treatment, though drug interactions may be problematic. (Interactions have been noted with trimethoprim, ranitidine, cimetidine, furosemide, and digoxin.)

Vanadium
This is a trace mineral present virtually everywhere. It seems to have insulin-like properties and minimal side effects potential but is not likely to be helpful by itself. The form that has been studied was vanadium dipicolinate, which is not commercially available. The vitamin stores sell vanadium sulfate (Vanadyl Fuel®) but we do not know if it works as well as the dipicolinate form did in the research setting. 

Chromium Picolinate
This product is a mineral supplement that can be found in many vitamin stores. It seems to potentiate the effects of insulin (i.e., the insulin becomes stronger). In cats, chromium picolinate would be used similarly to vanadium, i.e., as a supplement to insulin therapy.

Photo Courtesy of Dr. Teri Ann Oursler

Acarbose (Glucobay®, Precose®)
This medication inhibits the digestive enzymes responsible for breaking down starches. Its use leads to a more gradual absorption of sugars after a meal, which in turn leads to a more stable blood sugar level. The medication itself is not absorbed from the intestine and thus can be combined with other medications, but it can produce some intestinal side effects: flatulence, weight loss, and diarrhea. Acarbose was originally developed as a treatment for obesity since it interferes with sugar absorption and should not be used in underweight cats. Acarbose must be given with food if it is to work. Acarbose can be used in both dogs and cats.

Dietary Therapy

In cats, one of the most important aspects of managing diabetes mellitus is using a low-carbohydrate diet, and it would be incomplete, not to mention it here. Most experts feel that this change alone is more significant in regulating diabetic cats than any of the above supplements and medications combined. Diet in a diabetic cat should not be taken lightly; if you have not done so already, see current recommendations in this regard.

Dietary therapy is also important for dogs but in a different way. Rather than a focus on low-carbohydrate diets, high-fiber diets have been found to be more helpful.