Abstract
Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are prescribed to manage hyperinsulinemia but the effects of dapagliflozin have not been investigated. Although hyperlipaemia is very rare, hypertriglyceridemia is commonly associated with SGLT2i treatment and investigation of the lipoprotein profiles is warranted.
Methods: Retrospective analysis of clinical records and stored serum from horses with hyperinsulinemia that received dapagliflozin (0.02 mg/kg, [n = 34]) or ertugliflozin (0.05 mg/kg [n = 24]) PO SID for 30 days. Within-horse changes, correlations between variables, and differences between treatments were assessed using Wilcoxon signed-rank, Spearman's rank correlation coefficient (rho) and the medians tests, respectively.
Results: Between day 0 (pre-treatment) and day 30 within-horse changes (median, inter-quartile range [IQR]) were: basal serum [Insulin] (uU/mL) reduced from 170 (92-280) to 28.7 (14.5-90) (P < .0001), lameness grade (scale 0-12) reduced from 6 (4-10) to 2 (0-2) (P < .001), serum [triglyceride] (mmol/L) increased from 0.5 (0.3-0.6) to 1.0 (0.6-1.56), [β-hydroxybutyrate] (μmol/L) increased from 0.22 (0.17-2.7) to 0.30 (0.24-0.35) (P < .0001), [total cholesterol] (mmol/l) increased from 2.36 (2-2.6) to 2.84 (2.4-3.7) (P < .0001) and, as a percentage of serum lipids, high-density lipoprotein (HDL) reduced from 52.4% (47.9%-61.0%) to 50% (41%-54.8%) (P = .034), very-low density lipoprotein (VLDL) increased from 10.4% (6.4%-14.4%) to 12.3% (9.9%-16.8%) (P = .005). Differences between ertugliflozin and dapagliflozin groups in these parameters were not significant at day 0 or 30. At day 30, 10/48 (21%) cases had [triglycerides] >2.0 mmol/L (maximum = 10.8 mmol/L). Day 30 [triglyceride] was correlated with day 0: basal insulin (P < .001, rho = 0.47), [triglyceride] (P = .003, rho = 0.42) and %VLDL (P = .019, rho = 0.34) and day 30: [total cholesterol] (P < .001, rho = 0.67), %HDL (rho = −0.432, P = .014) and %VLDL (rho = 0.708, P < .001).
Discussion and clinical relevance: Dapagliflozin or ertugliflozin treatment is associated with reductions in [insulin] and lameness grade. Changes in [triglyceride] and lipoprotein profiles were usually minor with occasional marked hypertriglyceridemia. [β-hydroxybutyrate] increased indicating ketosis, a metabolic pathway previously not thought to be relevant in horses.
ORAL PRESENTATION ACVIM Resident Research Abstract Award Winner