Efficacy and safety of once daily oral administration of sodium-glucose cotransporter-2 inhibitor velagliflozin compared with twice daily insulin injection in diabetic cats.

Abstract

BACKGROUND: Options for treatment of diabetes mellitus in cats are limited to insulin injections and monitoring for hypoglycemia. HYPOTHESIS: Once daily sodium-glucose cotransporter-2 inhibitor velagliflozin PO is noninferior to insulin injections. ANIMALS: Client-owned diabetic cats (127 safety; 116 efficacy assessment). METHODS: Prospective, randomized (1&#x2009;mg/kg velagliflozin), positive controlled (titrated Caninsulin), open label, noninferiority field trial, comparing number of cats with treatment success in &#x2265;1 clinical variable and &#x2265;1 glycemic variable (margin &#x394;: 15%) on Day 45; secondary endpoints included glycemic and clinical assessments during 91&#x2009;days. RESULTS: On Day 45, 29/54 (54%) velagliflozin-treated cats and 26/62 (42%) Caninsulin-treated cats showed treatment success, demonstrating noninferiority (difference -11.8%; upper 1-sided 97.5% confidence interval, -&#x221e; to 6.3%). By Day 91, quality of life (QoL), polyuria, and polydipsia had improved in 81%, 54% and 61% (velagliflozin); on blood glucose (BG) curves, mean BG was <252&#x2009;mg/dL in 42/54 (78%; velagliflozin) and 37/62 (60%; Caninsulin); minimum BG was <162&#x2009;mg/dL in 41/54 (76%; velagliflozin) and 41/62 (66%; Caninsulin); serum fructosamine was <450&#x2009;&#x3bc;mol/L in 41/54 (76%; velagliflozin) and 38/62 (61%; Caninsulin). Velagliflozin's most frequent adverse events were loose feces/diarrhea (n&#x2009;=&#x2009;23/61, 38%), positive urine culture (n&#x2009;=&#x2009;19/61, 31%), and nonclinical hypoglycemia (BG <63&#x2009;mg/dL; n&#x2009;=&#x2009;8/61, 13%); Caninsulin's: clinical and nonclinical hypoglycemia (n&#x2009;=&#x2009;35/66, 53%), positive urine culture (n&#x2009;=&#x2009;18/66, 27%), and loose feces/diarrhea (n&#x2009;=&#x2009;10/66, 15%). Diabetic ketoacidosis occurred in 4/61 (7%; velagliflozin) and 0/66 (Caninsulin). CONCLUSIONS AND CLINICAL IMPORTANCE: Once daily oral administration of velagliflozin was noninferior to insulin injections, showed good QoL and glycemia without clinical hypoglycemia.