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

Sundra, T; Knowles, E; Rendle, D; Kelty, E; Lester, G; Rossi, G

Abstract

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), [beta-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.

Citation

Sundra, T., Knowles, E., Rendle, D., Kelty, E., Lester, G., & Rossi, G. (2025). Short-term clinical and biochemical responses following treatment with dapagliflozin or ertugliflozin in horses with hyperinsulinemia: A retrospective case series. Domestic Animal Endocrinology, 90, https://doi.org/10.1016/j.domaniend.2024.106894

• Journal Article Type: Article
• Acceptance Date: Nov 15, 2024
• Online Publication Date: Nov 19, 2024
• Publication Date: 2025
• Deposit Date: Jan 24, 2025
• Publicly Available Date: Jan 24, 2025
• Print ISSN: 0739-7240
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 90
• DOI: https://doi.org/10.1016/j.domaniend.2024.106894
• Keywords: Equine; Laminitis; Lipoprotein; SGLT2 inhibitor; GLUCOSE COTRANSPORTER-2 INHIBITORS; SGLT2 INHIBITORS; GLYCEMIC CONTROL; TYPE-2; HYPERLIPEMIA; CANAGLIFLOZIN; WEIGHT; PONIES