LECTURE TITLE: SGLT-2 INHIBITORS: FINALLY AN ALTERNATIVE TO INSULIN

INJECTIONS IN DIABETIC CATS?

Speaker Name: Stijn Niessen

University or Company: VIN Europe, VSC & Royal Veterinary College London
Department:
Address: Loosdrechtseweg 56, Hilversum
Country: Netherlands

INTRODUCTION

Treatment options for feline diabetes mellitus are limited and usually involve insulin injections and careful
monitoring to avoid hypoglycaemia. This does have important cat-owner bond implications as well as
significant lifestyle and cost consequences for the owner. After diagnosis of diabetes and start of insulin
therapy, most owners need to be at home twice daily to inject the insulin, they cannot easily hand over
the care to go and have a relaxing weekend away from home and the inherent risk for hypoglycaemia
means we need to be regularly checking for hypoglycaemia in any cat on insulin injection therapy.

Sodium-glucose-co-transporter-2-inhibitors (SGLT-2-inhibitors) form a new category of anti-diabetes

drugs. For humans with type 2 diabetes mellitus this category has proven very useful and it has become
standard of care for many people.
Increasingly veterinary studies with SGLT2 inhibitors have been conducted showing its promise for use in
cats with diabetes mellitus. Two will or have gained licensing: velagliflozin (EU, UK, Switzerland and
USA) and bexagliflozin (USA). The author was directly involved in the largest randomised controlled study
to date with an oral once daily SGLT-2-inhibitor called velagliflozin. The hypothesis was that it could be an
alternative to insulin injections without inferior clinical, glycemic, safety and quality of life (QoL) effects.
As such, a prospective field study was conducted, involving 127 client-owned diabetic cats (127/127
safety assessment; 116/127 efficacy assessment), randomized to 1 mg/kg oral SID velagliflozin liquid or
titrated BID caninsulin injections. The primary efficacy outcome involved assessment for non-inferiority
(margin Δ: 15%) of velagliflozin compared to caninsulin on day 45; secondary endpoints included
glycemic and clinical assessments during 91 days.
On day 45, 29/54 (53.7%) of velagliflozin-treated cats and 26/62 (41.9%) of caninsulin-treated cats showed
treatment success, proving non-inferiority (non-inferiority margin –11.8; upper one-sided 97.5%-confidence
interval -∞, 6.34). By day 91, QoL, and polyuria/polydipsia had improved in most cats; on blood glucose
(BG) curves, mean BG was <14 mmol/L in 43/54 (79.6%) (velagliflozin), 38/62 (61.3%) (caninsulin);
minimum BG <9 mmol/L in 42/54 (77.8%) (velagliflozin) and 42/62 (67.7%) (caninsulin); serum
fructosamine <450 μmol/L in 41/54 (75.9%) (velagliflozin) and 38/62 (61.3%) (caninsulin).
Most frequent adverse events for velagliflozin were: loose stools/diarrhea (n=23, 37.7%), positive urine
culture (n=19, 31.1%), and non-clinical hypoglycemia (n=8, 13.1%); for caninsulin: clinical and non-clinical
hypoglycemia (n=35, 53.0%), positive urine culture (n=21, 31.8%) and loose stools/diarrhea (n=10,
15.2%). In four velagliflozin-cases, and in none of the caninsulin-cases, suspected DKA was diagnosed
(cats appeared ill and showed ketonuria; three were naïve cases; one was insulin pre-treated); all presented
with euglycemia and three of four events occurred within the first week after velagliflozin start. In three of
four cases DKA-treatment was allowed by the owner which proved successful in all.
This field study has therefore shown that diabetes mellitus can be successfully treated with once daily
oral velagliflozin in most cats and is associated with marked sustained decreases in glycemic parameters,
no need to titrate dose, no clinical hypoglycemia and improved QoL. Main side effect of note is loose
stools. DKA seems rare and mostly occurs soon after treatment start (less than 2 weeks after start),
implying initial regular screening for ketonuria or ketonemia is advisable.
This category of drug is due to revolutionise how we treat a majority of diabetic cats. Given its
characteristics, it will be perceived to be more owner friendly. This in turn will lead to less euthanasia
among diabetic cats.

REFERENCES
1. S.J.M. Niessen, H.S. Kooistra, Y. Forcada, C.R. Bjørnvad, B. Albrecht, F. Rössner, E. Herberich,
C. Kroh; Efficacy and safety of once daily oral sodium-glucose co-transporter-2-inhibitor
velagliflozin compared to twice daily insulin injection therapy in diabetic cats; Journal of
Veterinary Internal Medicine; Nov 2022; Pages 1847-2551.
2. Hadd MJ, Bienhoff SE, Little SE, Geller S, Ogne-Stevenson J, Dupree TJ, Scott-Moncrieff JC.
Safety and effectiveness of the sodium-glucose cotransporter inhibitor bexagliflozin in cats newly
diagnosed with diabetes mellitus. J Vet Intern Med. 2023 May-Jun;37(3):915-924. doi:
10.1111/jvim.16730. Epub 2023 May 6. PMID: 37148170; PMCID: PMC10229323.
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