Diabetes Mellitus: Oral Treatments for Cats

What is diabetes mellitus?

Diabetes mellitus (DM) is a failure of the body to regulate blood sugar levels. Blood sugar is regulated by insulin, a hormone produced by beta cells in the pancreas. Insulin acts as a key, unlocking cells to allow sugar from the bloodstream into the tissues of the body.

What type of diabetes is the most common in cats?

Type II diabetes is the most common type of DM in cats. It is often due to insulin resistance, a condition in which the pancreas secretes insulin, but the body’s tissues don’t respond well, causing reduced sugar uptake and more sugar (or glucose) remaining in the bloodstream. 

The pancreas responds to that higher blood sugar by producing more insulin, initially compensating for the resistance. Unfortunately, this requirement for higher and higher levels of insulin leads to exhaustion of the beta cells (insulin-producing cells) and eventually cellular damage from constant high glucose levels (glucose toxicity).

Some diabetic cats lose their need for insulin after their blood sugar is controlled by insulin injections, because their beta cells get a chance to recover and produce insulin again. Also, if a cat’s body weight becomes closer to ideal, their tissues become more sensitive to insulin, further keeping blood sugar levels down.

What oral treatments can be useful in cats with DM?

New medications have been approved to help regulate blood glucose levels in cats, including once-daily oral medications bexagliflozin (Bexacat®) and velagliflozin (Senvelgo®). Normally, kidneys are excellent at re-absorbing glucose as they filter waste from the blood into the urine. These medications interfere with this process, preventing the kidneys from re-absorbing as much glucose as they normally would, causing blood sugar levels to fall to normal levels, and reducing the constant stress on beta cells in the pancreas.

What cats may benefit from these oral treatments?

Cats in the initial stages of DM may benefit most from oral diabetes treatments. These cats are more likely to have functional but exhausted beta cells in their pancreas. By lowering blood glucose levels, these medications give the beta cells a break. With time, the beta cells will start to produce insulin again, helping sugar in the blood to enter the cells of the body.

What cats are not good candidates for these treatments?

Cats who cannot make enough insulin are considered insulin-dependent and won’t respond well to these new medications, as they need insulin supplementation (by injection) to function. Without enough insulin, the body’s tissues can’t get enough glucose to support their function. Unfortunately, there is no test currently available to determine if a cat is making enough insulin. Generally, the longer a cat has had DM, the more likely they are to be insulin-dependent, and the less likely they are to respond to oral treatments.

"Cats that are sick when diagnosed are not good candidates for oral treatments."

Cats that are sick when diagnosed are not good candidates for oral treatments. Cats need to be evaluated for pancreatitis, hyperthyroidism, hypertension, urinary tract infection, other infections, and cancer before starting this treatment. This treatment is also not recommended for cats with stage 3 or 4 kidney failure, geriatric cats, or cats with pancreatitis.

What are the downsides to this treatment?

These treatments lower blood sugar levels, but they don’t help glucose get into cells. If your cat can’t produce enough insulin, there is still a risk of it developing diabetic ketoacidosis (DKA) or euglycemic DKA.

How must my cat be monitored when using oral medications for DM?

Before starting oral medication for DM, your cat will undergo baseline testing that may include a complete blood count, biochemistry profile, T4 (thyroid), blood ketones, urine culture, urinalysis to screen for urine ketones, blood pressure measurement, and abdominal ultrasound (if available). Your veterinarian will recommend specific testing for your cat. Ketones are especially important in monitoring your cat’s response to this medication.

Your veterinarian will let you know how frequently your cat needs to come to the clinic for monitoring, including physical examinations and lab testing. Typically, your cat will be reassessed several times during the first two weeks of starting treatment, then a month after starting treatment. If your cat responds well, your veterinarian may then recommend rechecks every three to four months.

Report any signs of illness to your veterinarian immediately; they generally warrant follow-up exam and testing.

What are ketones and why are they important?

When the body is deprived of glucose, it breaks down fat to produce ketones for energy. Glucose deprivation can result from starvation, but can also happen when the body loses its ability to absorb glucose, as happens with DM. As ketone levels increase, they cause a shift in the body’s electrolyte balance and can cause weakness, nausea, vomiting, and dehydration – signs known as diabetic ketoacidosis (DKA). In extreme cases, DKA can cause death. DKA treatment requires insulin – oral hypoglycemics will not resolve the condition.

"DKA treatment requires insulin – oral hypoglycemics will not resolve the condition."

When a cat is treated with oral DM medications, a ketone called beta-hydroxybutyrate is monitored closely. Increasing levels of this ketone indicate that the cat doesn’t have enough residual insulin production to regulate their glucose and that they require insulin therapy.

This ketone is also crucial to monitor if your pet shows any signs of DKA while taking oral DM medication, as they won’t have the typical hyperglycemia (high blood glucose) normally associated with the condition.

What can I expect after my cat starts the medication?

Typical clinical signs of DM include weight loss, increased drinking, increased urination, and increased appetite. Any or all of these signs may resolve with treatment.

Adverse effects include soft stool, diarrhea, vomiting, decreased appetite, lethargy, dehydration, and increased risk of urinary tract infections. Let your veterinarian know of any changes you notice while your cat is taking one of these medications.

If these medications don’t result in better glucose control (as demonstrated by glucose curves or fructosamine levels), or if your cat loses weight, has increasing levels of beta-hydroxybutyrate (ketones), or has uncontrollable diarrhea, then a switch to traditional insulin treatments is needed.

Because these medications are new, we do not know all the outcomes, which makes it even more critical to follow your veterinarian’s recommendations for monitoring and to keep them updated about any changes.