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 mg/kg velagliflozin), positive controlled (titrated Caninsulin), open label, noninferiority field trial, comparing number of cats with treatment success in ≥1 clinical variable and ≥1 glycemic variable (margin Δ: 15%) on Day 45; secondary endpoints included glycemic and clinical assessments during 91 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, -∞ 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 mg/dL in 42/54 (78%; velagliflozin) and 37/62 (60%; Caninsulin); minimum BG was <162 mg/dL in 41/54 (76%; velagliflozin) and 41/62 (66%; Caninsulin); serum fructosamine was <450 μmol/L in 41/54 (76%; velagliflozin) and 38/62 (61%; Caninsulin). Velagliflozin's most frequent adverse events were loose feces/diarrhea (n = 23/61, 38%), positive urine culture (n = 19/61, 31%), and nonclinical hypoglycemia (BG <63 mg/dL; n = 8/61, 13%); Caninsulin's: clinical and nonclinical hypoglycemia (n = 35/66, 53%), positive urine culture (n = 18/66, 27%), and loose feces/diarrhea (n = 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.

Keywords: antidiabetic; beta‐cell; compliance; feline diabetes mellitus; glucosuria; glucotoxicity; glycemic control; prospective clinical trial; sodium‐glucose cotransporter‐2 (SGLT2) inhibitor.

FIGURE 1

Results of the inclusion/exclusion process of the study. DKA, diabetic ketoacidosis; FAS, full analysis set.

FIGURE 2

Improvement rates compared with screen (%) inrurine frequency/volume (A), water consumption (B), appetite (C) and palmigrade/plantigrade stance (D).

FIGURE 3

Change in body conditions score (BCS; 1‐9) over time in velagliflozin‐ and insulin‐treated diabetic cats over time.

FIGURE 4

Fructosamine, mean blood glucose, and minimum blood glucose (BG) over time in the full analysis set, and in the subgroups of naïve and insulin‐pretreated cats in the velagliflozin and insulin groups. Error bars represent adjusted mean ± standard error (SE) from mixed model repeated measures (MMRM) analysis.

FIGURE 5

Mean blood glucose for each time point of the blood glucose (BG) curves in the full analysis set, and in the subgroups of naïve and pretreated cats. Error bars represent mean ± standard deviation (SD).

FIGURE 6

Change compared with screening in quality of life in all cats, and in the subgroups of naïve and insulin‐pretreated (pre‐trd) cats in the velagliflozin and insulin groups.