What the new AAHA Diabetes Management Guidelines for Cats say about SGLT2 inhibitors

"My hierarchy in choosing a treatment for a diabetic cat no longer starts with insulin,” Renee Rucinsky, DVM, DABVP, cochair of the 2026 AAHA Diabetes Management Guidelines for Cats task force, said in an American Animal Hospital Association (AAHA) Trends report, summing up a shift that's been building for years.¹ “I plan on treating with an SGLT2 [inhibitor] first because of its overall safety and efficacy. I look for reasons I shouldn't use it, not reasons I should."

Published in the May/June 2026 issue of the AAHA journal, the guidelines formalize that shift with detailed recommendations on patient selection, monitoring, diet, and when to transition patients to insulin.

Who qualifies, and who doesn't

Two SGLT2 inhibitors are FDA-approved for newly diagnosed cats with diabetes that have never received insulin. Bexagliflozin is available as a tablet while velagliflozin is an oral solution. Both are administered once daily. The guidelines describe them as "an appropriate treatment option for a substantial proportion of patients" but also draw clear boundaries around which cats should receive them.

Cats that are eating well, well hydrated, and otherwise clinically stable are good candidates for SGLT2 inhibitor therapy. Cats with systemic compromise—including vomiting, poor appetite, lethargy, or cachexia—should instead begin insulin therapy. Insulin is also recommended for cats with hepatopathy, advanced chronic kidney disease (IRIS Stage 3), or hypercalcemia. Any cat older than 7 years should be screened for hyperthyroidism before treatment.

Cats with readily reversible causes of insulin resistance, such as recent depot steroid administration, are especially good candidates, according to the guidelines. These cats are more likely to achieve remission once the underlying cause is addressed and are at greater risk for hypoglycemia with insulin, making SGLT2 inhibitors a safer starting point. Feline patients with acromegaly may also be candidates, although the task force recommends consulting a specialist first.

Screen for ketosis before starting

Before treatment begins, every cat should have a blood beta-hydroxybutyrate (BHB) measurement. The guidelines call BHB testing "an essential part of SGLT2 inhibitor drug monitoring" because it is more reliable than urine dipstick testing for detecting early ketosis.

The bexagliflozin label advises against initiating treatment if BHB exceeds 3.6 mmol/L, or 2.4 mmol/L in cats with a history of acidosis or kidney compromise. Both drugs' labels also advise against treatment if ketonuria is present.

Monitoring: BHB, not blood glucose

Once treatment begins, monitoring priorities are different from what most clinicians are used to. Because hypoglycemia is uncommon with SGLT2 inhibitors, routine glucose curves are generally unnecessary. During the first 2 weeks, monitoring blood BHB over blood glucose is significantly more important.

The reason is that cats receiving SGLT2 inhibitors can develop diabetic ketoacidosis without elevated blood glucose, a condition known as euglycemic diabetic ketoacidosis (EDKA). Although its incidence is similar to that seen in insulin-treated cats, the lack of hyperglycemia can make the condition harder to recognize, increasing the risk of progressive illness if treatment is delayed.

Daily BHB monitoring is recommended during the first 2 weeks of treatment, when most cases of DKA and EDKA develop. A mild increase in BHB of less than 20% above baseline during the first 3 days may be acceptable if the cat is eating normally, appears clinically well, and can be monitored daily.

After the first 3 days, treatment should continue only if BHB remains stable and the cat remains clinically well.

"Continued use of an SGLT2 inhibitor in the presence of clinical signs of illness, persistently increasing BHB concentrations after the first 3 days of therapy, or a lack of appropriate BHB monitoring puts the patient at marked risk for DKA," the guidelines state.²

How well does it work?

For appropriate candidates, clinical improvement is often quick. Blood glucose improves within hours of the first dose in most cats with diabetes, and fructosamine concentrations are routinely within the reference range after 8 weeks. Persistent polyuria and polydipsia also improve despite ongoing glucosuria. More than 75% of cats with peripheral neuropathy, often characterized by a plantigrade stance, showed improvement with velagliflozin treatment.

Response should be reassessed after 1 month. Cats that remain hyperglycemic and continue to show clinical signs should discontinue the drug and begin insulin therapy.

Diet during treatment

Diet changes should wait. Patients should remain on their usual diet during the first 2 weeks of treatment. If they're doing well, clinicians can gradually transition them to a low-carbohydrate diet.

Although comparable feline data are lacking, the recommendation reflects experience in human medicine, where carbohydrate restriction during SGLT2 inhibitor therapy is discouraged.²

The most common adverse effect

Changes in stool consistency are the most commonly reported adverse effect, affecting 38% to 50% of cats during the first 2 weeks. Diarrhea is thought to result from mild cross-inhibition of a related transporter in the small intestine, creating an osmotic effect. Antibiotics are not indicated.

In most cases, diarrhea resolves on its own and can be managed with a temporary 25% dose reduction or short-term dietary adjustment. Cats with persistent diarrhea that does not improve may need to transition to insulin.

Some cats may also experience vomiting, but episodes are generally sporadic. The guidelines note that if a cat vomits within 30 minutes of dosing and is otherwise clinically stable, redosing is considered safe. A small number of cats have also shown modest increases in serum calcium. For cats with a history of hypercalcemia, monitoring ionized calcium is recommended.

When to stop

Cats that remain hyperglycemic after 1 month of treatment and continue to show clinical signs should discontinue the drug and begin insulin the following day. Before determining the medication has failed, clinicians should confirm the cat is receiving the full dose. Mixing the medication into a full meal can lead to underdosing if the cat doesn't finish eating.

Persistent hypercalcemia or severe hyperlipidemia are also reasons to discontinue therapy and transition to insulin.

"When used appropriately, management with SGLT2 inhibitors can make diabetes pretty boring,” Rucinsky said in an AAHA Trends report.²

References

1. Seymour KG. Now available: 2026 AAHA Diabetes Management Guidelines for Cats. American Animal Hospital Association. April 27, 2026. Accessed June 26, 2026. https://www.aaha.org/trends-magazine/publications/coming-soon-2026-aaha-diabetes-management-guidelines-for-cats/
2. Bugbee A, Rucinksy R, Alvarez E, et al. the 2026 AAHA Diabetes Management Guidelines for Cats. American Animal Hospital Association. Accessed June 26, 2026. https://www.aaha.org/resources/2026-aaha-diabetes-management-guidelines-for-cats/