Short-term clinical and biochemical responses following treatment with dapagliflozin or ertugliflozin in horses with hyperinsulinemia: A retrospective case series

The metabolic and lipid profiles of horses treated with sodium-glucose cotransporter 2 inhibitors are not well understood. This retrospective study evaluated blood parameters in hyperinsulinemic horses treated with either ertugliflozin (0.05 mg/kg) or dapagliflozin (0.02 mg/kg) orally once daily. Blood samples were collected at baseline (day 0) and after 7 and/or 30 days of treatment. Statistical analyses were conducted using Wilcoxon signed-rank, Mann-Whitney and Spearman's rank correlation tests. Thirty-four horses received dapagliflozin and 24 received ertugliflozin. Significant (p<0.05) within-horse changes between day 0 and day 30 included [median, inter-quartile range (IQR)]: basal serum [Insulin] (uU/ml) reduced 170 (92-280) to 28.7 (14.5-90); [triglycerides] (mmol/l) increased 0.5 (0.3-0.6) to 1.0 (0.6-1.56), [β-hydroxybutyrate] (umol/l) increased 0.22 (0.17-2.7) to 0.30 (0.24-0.35); [total cholesterol] (mmol/l) increased 2.36 (2-2.6) to 2.84 (2.4-3.7); and GGT (IU/ml) increased 21 (16-32) to 25 (18-38). As a percentage of total serum lipids, high-density lipoprotein (HDL) reduced 52.4 % (47.9 %-61.0 %) to 50 % (41 %-54.8 %) and very-low density lipoprotein (VLDL) increased 10.4 % (6.4 %-14.4 %) to 12.3 % (9.9 %-16.8 %) (all p<0.05). Differences between ertugliflozin and dapagliflozin groups were not significant in any of these parameters at days 0, 7 or 30. At day 30, 10/48 (21 %) cases had [triglycerides] > 2.0 mmol/l (maximum = 10.8mmol/l). Day 30 [triglyceride] correlated with day 0: basal insulin (rho=0.47); [triglyceride] (rho=0.42); %VLDL (rho=0.34) day 30: [total cholesterol] (rho=0.67), %HDL (rho=-0.432) and %VLDL (rho=0.708). Our findings suggest that SGLT2 inhibitors induce minor changes in lipid profiles, with occasional cases of marked hypertriglyceridemia, and that dapagliflozin and ertugliflozin exhibit similar biochemical effects.