Dear Veterinarian,

We want to inform you of a new product the U.S. Food and Drug Administration (FDA) recently approved, as well as important safety conditions, including those that require emergency intervention, associated with its use. Bexacat (bexagliflozin tablets) is a new animal drug used to improve glycemic control in otherwise healthy cats with diabetes mellitus not previously treated with insulin.

Bexacat is the first oral diabetes treatment approved for cats in a new class of drugs known as sodium-glucose cotransporter 2 (SGLT2) inhibitors. An SGLT2 inhibitor is not insulin and is not for use in cats with insulin-dependent diabetes mellitus. Before using Bexacat, read the entire product insert, including the boxed warning describing the need for appropriate patient selection and the potential for severe adverse reactions.

Based on data from field studies, the FDA has concluded that Bexacat may cause an increased risk of diabetic ketoacidosis (DKA) or euglycemic DKA in cats. Euglycemic DKA is a life-threatening emergency that is characterized by euglycemia, metabolic acidosis, and ketoacidosis. Unlike DKA, the diagnosis of euglycemic DKA may be overlooked because of the absence of hyperglycemia.

Bexacat works by blocking the reabsorption of glucose by the kidney, increasing glucose excretion, and lowering blood glucose levels in diabetic cats who have elevated blood glucose levels. The data from two 6-month field studies and an extended use field study demonstrated that Bexacat was over 80 percent effective in improving glycemic control in cats with diabetes mellitus. Although there are notable safety concerns with the use of Bexacat, they can be mitigated by carefully screening cats before starting the drug, continued diligent monitoring regardless of the duration of or response to treatment, and knowing how to promptly recognize and appropriately treat serious and life-threatening adverse reactions. 

The following are summaries of important information from the product labeling:

CONTRAINDICATIONS: Bexacat should not be used in cats with diabetes mellitus who have previously been treated with insulin, who are receiving insulin, or in cats with insulin-dependent diabetes mellitus. The use of Bexacat in cats with insulin-dependent diabetes mellitus, or the withdrawal of insulin and initiation of Bexacat, is associated with an increased risk of diabetic ketoacidosis (DKA) or euglycemic diabetic ketoacidosis (DKA with a normal blood glucose concentration) and death. Bexacat also should not be used in cats with evidence of hepatic disease or reduced renal function. 

WARNING: Bexacat should not be initiated in cats with anorexia, dehydration, or lethargy at the time of diagnosis of diabetes mellitus or without appropriate screening tests, as detailed in the package insert. Based on data from field studies, the FDA has concluded that Bexacat may cause an increased risk of diabetic ketoacidosis or euglycemic diabetic ketoacidosis in cats. As DKA and euglycemic DKA in cats treated with Bexacat may result in death, development of these conditions should be treated promptly and requires the following actions: 

• Discontinuation of Bexacat;
• Prompt initiation of insulin therapy;
• Administration of dextrose or other carbohydrate source, regardless of blood glucose concentration; and
• Appropriate nutritional support should be promptly initiated to prevent or treat hepatic lipidosis.

Delay in recognition and treatment of DKA and euglycemic DKA may result in increased morbidity and mortality. Due to reduced clearance in some cats with potentially clinically undetectable hepatic disease and/or reduced renal function at the time of Bexacat initiation, some cats may exhibit glucosuria and/or euglycemia despite discontinuation of Bexacat. Persistent glucosuria results in osmotic diuresis and dehydration that may require treatment, including protracted hospitalization for DKA, euglycemic DKA, or hepatic lipidosis. 

Cats should be screened for urinary tract infections and treated, if indicated, when initiating Bexacat. Treatment with Bexacat may increase the risk for urinary tract infections. Cats should be monitored for urinary tract infections and treated promptly. Consider discontinuation of Bexacat in cats with recurrent urinary tract infections. The long-term use of Bexacat may increase the risk of urothelial carcinoma.

MONITORING: Sudden onset of hyporexia/anorexia, lethargy, dehydration, or weight loss in cats receiving Bexacat should prompt immediate discontinuation of Bexacat and assessment for diabetic ketoacidosis, regardless of blood glucose level. During treatment with Bexacat, blood glucose, fructosamine, serum β-hydroxybutyrate (BHBA), serum feline pancreas-specific lipase (fPL), liver parameters, serum cholesterol and triglycerides, and body weight and clinical signs should be routinely monitored. The package insert describes recommendations regarding increasing or persistently elevated fPL, liver parameters, cholesterol, and triglycerides levels. If a notable reduction in BHBA is not observed after initiation of Bexacat, or if BHBA is persistently rising after an initial reduction, Bexacat should be discontinued. 

The package insert describes specific monitoring during the first 8 weeks of Bexacat therapy. Cats demonstrating poor glycemic control, including weight loss, an average blood glucose concentration from an 8-hour blood glucose curve ≥ 250 mg/dL, and/or a fructosamine level indicating poor glycemic control during the first 8 weeks should be closely monitored. Cats demonstrating poor glycemic control at 8 weeks should be discontinued from Bexacat and initiation of insulin considered. 

PRECAUTIONS: Consider temporary discontinuation of Bexacat in cats during times of decreased caloric intake, such as surgery or decreased appetite, as administration of Bexacat in these cats may increase the risk of diabetic ketoacidosis or hepatic lipidosis. Cats who develop diarrhea unresponsive to conventional therapy should have Bexacat discontinued.

INFORMATION FOR CAT OWNERS: Owners should be given the Client Information Sheet to read before Bexacat is administered. Owners should be informed that Bexacat may cause an increased risk of DKA and euglycemic DKA. Owners should be advised to discontinue Bexacat and contact a veterinarian immediately if their cat develops anorexia, lethargy, vomiting, diarrhea, or weakness.

The FDA’s Center for Veterinary Medicine (CVM) is committed to promoting and protecting animal health by ensuring safe and effective drugs are available for animals. For more information, please contact CVM’s Education & Outreach Staff at [email protected]. 

We urge veterinarians and pet owners to report side effects involving Bexacat to Elanco US Inc at 1-888-545-5973. For additional information about reporting adverse drug experiences for animal drugs, contact the FDA at 1-888-FDA-VETS or https://www.fda.gov/reportanimalae.

Sincerely, 

FDA’s Center for Veterinary Medicine