OST RESPONSES TO ERTUGLIFLOZIN Laboratory investigations
Blood was collected into serum and fluoride oxalate tubes for meas- urement of insulin and glucose, respectively. Samples were submit- ted to a commercial laboratory (NovaVet Diagnostics) on the same day the OST was performed. Clinical chemistry was performed prior to commencing treatment with ertugliflozin and at day 4 of treat- ment with insulin concentrations measured using an IMMULITE 2000xpi (Siemens). Creatinine, gamma-glutamyl transferase (GGT), glutamate dehydrogenase (GLDH) and triglyceride concentrations were measured using an AU480 (Beckman Coulter Australia Pty Ltd).
Data analysis
Signalment and clinical data from medical records were collated in Microsoft Excel (Microsoft Corporation). A nonparametric test was selected to assess responses on account of the small sample size and the lack of normally distributed data. Comparisons between pre- treatment values and day four measures were made using Wilcoxon matched-pairs signed rank tests. p -critical value was set at 0.05, with no adjustment made for multiple comparisons. Data analysis was carried out in Prism 9 (GraphPad Software).
RESULTS Horses
Sixteen horses with a history of laminitis and other signs suggestive of ID had an OST performed during the study period, with 10 that were identified to have ID being treated with ertugliflozin and also having a follow-up OST at day 4. Individual horse data is presented in Table 1 . At the commencement of treatment, median lameness grade from laminitis was 2/12 (range 0–6/12), median estimated
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body weight 305 kg (range 93–577 kg) and median body condition score 6/9 (range 4–8). All horses were being managed for ID for at least 3 months
prior to treatment with ertugliflozin. Programmes of restricted calorie intake had been implemented with all horses receiving low- sugar hay (Rhodes grass, lucerne or meadow hay) with water-sol- uble carbohydrate content of 6.5–10% fed at 1–2% body weight. A low-sugar ration balancer pellet (Hygain Zero or Hygain Meta Safe, Hygain) was also fed in accordance with manufacturer ' s rec- ommendations. Access to pasture was restricted and no changes in feed or management were implemented during the initial 4 days of treatment. Four horses had concurrent pituitary pars intermedia dysfunc-
tion (PPID) and were receiving treatment with pergolide (Prascend, Boehringer Ingelheim) at 2 mcg/kg (Table 1 ). Previously measured ACTH concentration demonstrated that the PPID was well man- aged. Three horses were receiving phenylbutazone paste (Bute Paste, Ranvet) at 1–2.2 mg/kg (Table 1 ) for lameness associated with laminitis when they commenced treatment with ertugliflozin.
Insulin
Insulin concentrations were lower at day 4 than pre-treatment across all time points (Table 2 ). Five horses (50%) had fasted (T0) insulin concentrations ≧20 uU/mL before commencing treatment, whilst at day 4, all horses had a fasted insulin concentration ≦20 uU/ mL. Insulin responses of individual horses across all three timepoints is depicted in Figure 1 .
Glucose
There was no statistically significant reduction in glucose con- centration (Table 2 ) following treatment at T0 ( p = 0.05) or T60
TABLE 1 Individual horse data including signalment, body condition score (BCS), pre-treatment lameness grade and concurrent medication use.
Horse Age (years) Breed 1
2 3 4 5 6 7 8 9
10
15 12 17 19 35 22 12 16 17 22
Sex
Miniature pony Welsh pony Appaloosa Andalusian Welsh pony Welsh pony Stockhorse
Welsh × Pony Arabian
Welsh × Pony Mare
Gelding Gelding Gelding Mare Mare Mare
Gelding Gelding Mare
BCS Pre-treatment lameness grade (/12) 4
6 8 7 6 7 6 5 6 6
2 2 4 6 0 0 2 0 4 2
Medications Phenylbutazone Pergolide N
N Y Y
N N N N Y
N
N N N Y Y Y
N N N Y
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