What is the evidence supporting bexagliflozin as an SGLT2 inhibitor for managing feline diabetes?

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Bexagliflozin (Bexacat) 15 mg PO q24h is FDA-approved as a sole oral therapy for uncomplicated feline diabetes mellitus (DM), achieving treatment success in 84% of newly diagnosed cats over a 6-month period. 45 The mechanism is insulin-independent. Bexagliflozin competitively inhibits sodium-glucose cotransporter 2 (SGLT2) in the renal proximal tubule, reducing glucose reabsorption and increasing urinary glucose excretion. The higher the blood glucose concentration, the greater the filtered glucose load and the more glucose excreted. 14 Pharmacokinetics in cats are relevant to dosing timing. Systemic exposure is 82% higher for peak plasma concentration (Cmax) and 54% higher for area under the curve (AUC) in the fasted versus fed state, so administration timing relative to meals affects exposure. Median time to peak plasma concentration is approximately 0.5 hours (range 0.5–2 hours) and mean half-life is approximately 5 hours. There is no drug accumulation with daily dosing in healthy cats, though some diabetic cats showed persistent blood levels after discontinuation, possibly related to decreased liver function in those individuals. 4 Glycemic efficacy is rapid and durable. A measurable decrease in blood glucose is detectable after the first dose, with durable reductions in mean blood glucose and fructosamine sustained across the 6-month study period. Serum beta-hydroxybutyrate decreased for the study population as a whole. 5 In cats with poorly regulated DM already receiving insulin, adding bexagliflozin produced a significant reduction in insulin dose requirement in all treated cats. 6 Clinical sign improvement is robust for polyuria and polydipsia but less consistent for polyphagia. Polyphagia is the sign least likely to improve, because the caloric wasting induced by SGLT2 inhibition drives compensatory hyperphagia. Neurological signs, musculature, and coat quality improved throughout the study period, and owner quality-of-life scores improved by study end. 5 H