Sodium-glucose cotransporter-2 (SGLT2) inhibitors block SGLT2, the renal transporter responsible for reabsorbing glucose from the glomerular filtrate back into circulation, thereby lowering the renal threshold for glucose and increasing urinary glucose excretion in an insulin-independent manner. FDA DailyMed An… This mechanism is distinct from insulin secretagogues and insulin sensitizers — glycemic control is achieved regardless of endogenous insulin status, though some residual β-cell function is still required to prevent ketosis when these drugs are used as monotherapy. Journal of Vete…+1

Two SGLT2 inhibitors are FDA-approved for veterinary use in cats: velagliflozin (Senvelgo, Boehringer Ingelheim) and bexagliflozin, both indicated for uncomplicated feline diabetes mellitus. Journal of Vete… Velagliflozin is formulated as a 15 mg/mL oral solution administered once daily at 1 mg/kg PO. FDA DailyMed An… Following oral dosing at 1 mg/kg in cats, peak plasma concentration is reached at a median of 0.25 hours, with a mean elimination half-life of 3.68 ± 0.34 hours. FDA DailyMed An… Systemic exposure is 170% higher for peak concentration and 45% higher for overall exposure in the fasted versus fed state, which is relevant to consistent dosing timing. FDA DailyMed An…

In cats with uncomplicated diabetes mellitus, velagliflozin produces rapid clinical improvement — more than 50% of cats show improvement in polyuria and polydipsia by day 7, rising to more than 88% by day 180, with polyphagia improved in 75% of cats at 180 days. Journal of the… Diabetic neuropathy (plantigrade stance) resolved in more than 75% of affected cats that completed the study. Journal of the… The paradoxical improvement in polyuria and polydipsia despite glucosuria occurs because the large reduction in blood glucose reduces the total glucose load filtered at the glomerulus, decreasing the osmotic force retaining water in the tubules. Journal of the…

Velagliflozin is also used off-label in horses and ponies with insulin dysregulation (ID). Treatment decreases blood insulin concentrations in ID-affected horses and ponies, and ponies treated with velagliflozin did not develop laminitis when subjected to a dietary challenge, in contrast to placebo-treated ponies. Journal of Vete…+1 The related SGLT2 inhibitors canagliflozin and ertugliflozin are also used in equine practice for insulin dysregulation. Journal of Vete…

Enavogliflozin (DWP16001) is under investigation as an adjunctive therapy in insulin-treated diabetic dogs with suboptimal glycemic control, defined as fructosamine ≥ 500 µmol/L and/or HbA1c > 6%, though comprehensive pharmacokinetic and safety data in dogs remain limited. BMC Veterinary… Canagliflozin has also been evaluated as an adjunct in insulin-treated diabetic dogs. Journal of Vete…

The critical safety constraint across all species is the risk of euglycemic diabetic ketoacidosis (DKA). In cats, approximately 75% of suspected DKA cases occur within the first 2 weeks of velagliflozin treatment. Journal of Vete… Cats that are completely insulin-deficient (type 1 diabetes mellitus) are at highest risk and should not receive SGLT2 inhibitors as monotherapy. FDA DailyMed An…+1 Additional adverse effects in cats include fecal softening to watery diarrhea (typically mild and self-limiting in the first week) and vomiting shortly after administration in approximately 1 in 3 cats, with 40% of those cats experiencing only a single episode. Journal of the…

Would you like to go through the patient selection criteria and monitoring protocol for starting velagliflozin in a newly diagnosed diabetic cat?