320
| Day 0
Insulin (uU/mL) T0
T60 T90
Glucose (mmol/L) T0
T60 T90
Triglycerides (mmol/L) GGT (U/L) GLDH (U/L)
Creatinine (umol/L) 22.4 (6.5, 39)
165 (61.2, 222) 170 (88.6, 269)
5.0 (4.8, 5.4) 7.7 (6.9, 8.6) 7.7 (6.3, 9.0) 0.4 (0.2, 0.7)
19.0 (14.5, 30.5) 4.5 (2.8, 8.3) 86.0 (77, 91)
Day 4 4.8 (3.7, 9.2)
78.1 (30.5, 137) 84.7 (28.7, 122)
4.9 (4.7, 5.0) 6.4 (6.0, 7.2) 6.6 (6, 7.1)
0.9 (0.6, 2.0)
18.5 (13.8, 28.3) 4.0 (2.8, 11.8) 88.0 (80.3, 104)
SUNDRA ET AL.
TABLE 2 Median and interquartile ranges for selected analytes prior to and after 4 days of treatment with ertugliflozin in horses with insulin dysregulation.
p -value
0.004 0.004 0.002
0.05 0.05 0.02
0.006 0.25 0.19 0.05
( p = 0.05). At T90, glucose concentration reduced from a me- dian of 7.7 mmol/L (IQR: 6.3, 9) prior to treatment to a median of 6.6 mmol/L (IQR: 6, 7.1) at day 4 of ertugliflozin treatment ( p = 0.02).
Triglycerides
Before treatment, triglyceride concentrations ranged from 0.2 to 2 mmol/L (median 0.4 mmol/L) with one horse having a triglycer- ide concentration above the laboratory reference interval
No adverse events were noted in association with ertugliflozin treatment. All horses tolerated the corn syrup administration and received the total dose on both occasions.
(0.05–
1.06 mmol/L; Table 2 ). Treatment with ertugliflozin was associated with an increase in triglyceride concentration ( p = 0.006) with results ranging from 0.3 to 3.8 mmol/L (median 0.9 mmol/L) at day 4. Five of the 10 horses (50%) had a concentration above the laboratory refer- ence interval at day 4.
Hepatobiliary and renal markers
Serum GGT concentration was outside the laboratory reference in- terval in a single horse on both days 0 and 4 (Table 2 ). One horse had an increased GLDH concentration (21 U/L) outside the laboratory reference interval (1–15 U/L) on day 4. There was no significant differ- ence in GGT ( p = 0.25) or GLDH ( p = 0.19) concentration between days 0 and 4. No horses had creatinine values that exceeded the normal reference intervals at either timepoint, and there was no difference in median creatinine concentration between day 0 and day 4 ( p = 0.05).
Lameness Prior to treatment,
DISCUSSION
The results of this study indicate that the administration of ertugli- flozin for 4 days is associated with significant reductions in fasted in- sulin concentrations and insulin responses to an OST in horses with ID. These findings compliment those of a previous study in which er- tugliflozin reduced post-prandial insulin concentrations in laminitic horses within 30 days (Sundra et al., 2023 ). Consistent with reports from clinical practice, the current study indicates a rapid reduction in insulin concentrations in association with ertugliflozin treatment with changes being seen much earlier than the 30 days reported pre- viously (Sundra et al., 2023 ). However, despite the significant reduc- tion in insulin concentration in this study, many horses still reported levels above the laboratory cut-off after treatment. It is currently unclear on the degree of insulin reduction required to be clinically relevant and significant interhorse variability likely exists. In a clini- cal setting, it would, therefore, be logical to interpret laboratory re- sults in light of the clinical response in order to gauge the response to therapy. A previous study suggested that the rapid improvement in lame-
the modified Obel lameness grade ranged from 0 to 6 with a median of 2. Following 4 days of treatment with
ness following ertugliflozin treatment is related to the reduction in insulin concentration (Sundra et al., 2023 ); however, in this study,
ertugliflozin there was no reduction in lameness grade ( p > 0.99). At both time points 7 of the 10 horses had a modified Obel grade ≧2. Pre-treatment lameness grades are included in Table 1 .
Adverse events
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