Breakthrough Veterinary Drug Senvelgo (Velagliflozin) expected to revolutionise the treatment of Feline Diabetes Mellitus in the United Kingdom

29 January 2024

By Laura Bree, Head of Internal Medicine, London Vet Specialists

Boehringer Ingelheim has launched Senvelgo, a once daily oral solution for the treatment of feline diabetes. Senvelgo decreases glucose resorption in the kidney with a resultant glucosuria and sustained reduced circulating blood glucose concentration of < 15 mmol/L (1). This drug may overcome some of the challenges facing owners and veterinarians in the management of diabetic cats with insulin, as well as reduced requirement for blood or interstitial glucose monitoring. Let’s take a closer look at this drug, how it works and what the initial data can tell us.

Senvelgo is a sodium-glucose co-transporter-2 (SGLT2) inhibitor. SLGT2 inhibitors bind to the high-capacity low affinity SLGT2 transporters in the proximal convoluted tubule of the kidney and inhibit glucose (and sodium) resorption from the ultrafiltrate. There are also SGLT1 transporters in the proximal convoluted tubule which resorb sufficient glucose to prevent hypoglycaemia when SGLT2 transporters are inhibited, but their low capacity results in incomplete glucose resorption with a resultant glucosuria. Increased glucosuria can achieve normoglycaemia which increases the likelihood of pancreatic beta cell recovery from glucotoxicity and increased endogenous insulin secretion. Increased endogenous insulin secretion allows the return of a more normal physiological management of carbohydrates, lipids and proteins. SGLT2 inhibitors were first approved for use in the management of type 2 diabetes mellitus in humans in 2013, in 2022 the first SGLT2 inhibitor was licensed in North America for use in cats and Senvelgo was licensed in Great Britain in 2023.

Exploring the physiology of feline diabetes aids in the understanding of how effective this drug is at treating feline diabetes. Cats most commonly develop a type 2-like diabetes mellitus which is multifactorial in origin and associated with progressive insulin resistance and pancreatic beta cell dysfunction and loss, which results in a relative lack of insulin (insufficient insulin for the degree of hyperglycaemia). Obesity, inactivity, and indoor lifestyle are believed to be major factors in developing insulin resistance in cats (2). Pancreatic beta cells become impaired and relative insulin deficiency develops by a combination inflammatory adipokines and glucotoxicity, and possibly amyloidosis. The beta cell dysfunction may improve if sustained normoglycaemia is achieved (3). This has traditionally been achieved using injectable insulin twice daily in combination with targeting insulin resistance through lifestyle change and weight management, diet, and sometimes oral hyperglycaemic therapies. The glucose peaks and troughs commonly associated with twice daily injections of insulin are limitations of the most common insulin protocols used in veterinary medicine and may delay or prevent recovery from beta cell dysfunction. It is also likely that a high proportion of cats with diabetes have undergone prolonged periods of hyperglycaemia prior to diagnosis, and this can result in beta cell apoptosis. The amount of beta cell loss at the time of diagnosis is likely to vary between cats, and beta cell loss in combination with beta cell dysfunction has historically determined the need for exogenous insulin whilst addressing the causes of insulin resistance.

The impact of diabetes on both owner and cat cannot be underplayed. Studies have detailed that of the 1 in 200 cats developing diabetes in the UK, 20 to 30% are euthanised within one year following diagnosis. This is due to a variety of factors but notably around 10 % are euthanised due to a decision not to use insulin, and a further 10% due to insulin compliance issues (4). The option of a once daily oral treatment will hopefully have a positive impact on these worrying statistics and provide an alternative therapy to owners that are unwilling or unable to use insulin.

Results from initial studies provide projected outcomes for cats receiving Senvelgo (1, 5). The pharmacological action of velagliflozin is to reduce blood glucose in a sustained manner and this is evident from initial clinical data. A prospective trial of 252 diabetic cats using velagliflozin demonstrated a sustained reduction in blood glucose over 180 days, by means of blood glucose and fructosamine measurement. The population consisted of newly diagnosed/naïve cats (85%) and insulin treated (15%) cats. After 6 months, 81% of cats had blood glucose and/or fructosamine concentrations within their respectively reference ranges.  Comparable glycaemic control has been demonstrated in another group of 26 cats, 50% of which were treated with twice daily lente insulin group and 50 % treated with once daily velagliflozin. At every re-examination over the following 2 months, velagliflozin treated cats had a mean lower blood glucose concentration at every visit (days 7, 14, 50 and 60) than those receiving insulin therapy. Furthermore, the sustained and regulated concentration of glucose was demonstrated in the velagliflozin group with blood glucose < 15 mmol/L over a 9-hour curve at both 30 and 60 days.

An important consideration before prescribing Senvelgo is an awareness of euglycaemic ketoacidosis. Insulin inhibits lipolysis and ketogenesis. A complete lack of insulin (or insulin dependence) cannot easily be estimated prior to therapy, but those who are unable to secrete sufficient endogenous insulin are likely to be more at risk for the development of ketosis / diabetic ketoacidosis (DKA). The increased glucosuria induced by Senvelgo, makes euglycaemic DKA a more likely presentation (although hyperglycaemic DKA is also possible). The recognition of this currently uncommon diabetic emergency will increase as we become accustomed to the use of velagliflozin. Early recognition is adapted into the product specifications and guidance for use of Senvelgo, with emphasis on checking urine ketones during the first few days and weeks of therapy, and as part of the long-term monitoring of this treatment (see flow chart). The outcomes of nearly 300 cats who received Senvelgo suggest around 7% of treated cats experience DKA, which typically occurs within the first 14 days after starting treatment (5). Any cat developing DKA when receiving Senvelgo should be transitioned to insulin and may require emergency treatment to manage their DKA.

Diarrhoea is a common side effect of Senvelgo, and this is suspected to be due to a cross over reactivity with gut SLGT1 cotransporters, which occurs in a dose dependent manner. In the field studies, this occurred in approximately 50 % of cats, three-quarters of which went on to have normal stools within the first four weeks of treatment. The diarrhoea appears to pose a minimal hindrance to treatment. Based on the current data, the risk of urinary tract infections does not seem increased, nor does the incidence of hypoglycaemia compared to traditional insulin treatments (1, 5). The presence of glucosuria is expected and decreases over time on therapy.

While Senvelgo is appropriately licensed for both newly diagnosed diabetic cats and those already on insulin, it is not recommended or appropriate to transition ‘happy’ cats who are stable and thriving on insulin therapy, to this medication. It is not indicated for any cat experiencing DKA during Senvelgo treatment, which supports an insulin deficiency, and therefore insulin dependent cat. It is yet to be determined if cats can then be transitioned to Senvelgo if they are first diagnosed with diabetes at the time of presenting in DKA and initially stabilised with insulin therapy.

Initiating Senvelgo requires monitoring, with a recommended schedule for ketonuria checks on days 1, 2, and 3 at home, along with assessments on days 7 and 14 at the veterinary practice.

There is sufficient evidence thus far to warrant the current excitement around the use of this new approach to feline diabetes. Using a treatment that can allow sustained control of hyperglycaemia is going to be a game changer for diabetic cats, and their owners. To support veterinarians navigating this novel approach to feline diabetes treatment, a 24-hour helpline is available from Boehringer Ingelheim, ensuring a seamless transition to Senvelgo and optimal care for our feline companions.

BSAVA Resources

Velagliflozin has just been added to the online and app versions of the BSAVA Canine and Feline Formulary https://www.bsavalibrary.com/content/dataitem/canine-and-feline/velagliflozin

Read more information on sodium-glucose co-transporter-2 (SGLT2) inhibitors in the feline diabetes mellitus chapter in the recently updated BSAVA Manual of Canine and Feline Endocrinology https://www.bsavalibrary.com/content/chapter/10.22233/9781910443866.chap24

References

  1. Niessen SJM et al. (2022) Once daily oral therapy for feline diabetes mellitus: evaluation of SGLT-2 inhibitor Velagliflozin as stand-alone therapy compared to insulin injection therapy in diabetic cats. Journal of Veterinary Internal Medicine 36, 2512–2513.
  2. O’Neill DG et al. (2016) Epidemiology of Diabetes Mellitus among 193,435 Cats Attending Primary-Care Veterinary Practices in England. Journal of Veterinary Internal Medicine. 30(4), 964-72.
  3. Gostelow R & Hazuchova K (2023) Pathophysiology of Prediabetes, Diabetes, and Diabetic Remission in Cats. Vet Clin North Am Small Anim Pract. 53(3), 511-529.
  4. Niessen SJM et al. (2017) The Big Pet Diabetes Survey: Perceived Frequency and Triggers for Euthanasia. Vet Sci. 4, 27.
  5. Behrend E et al. (2023) Velagliflozin, an SGLT2 Inhibitor, as Once-Daily, Oral Solution, Stand-Alone Therapy for Feline Diabetes Mellitus. ACVIM Forum Research Reports, Friday 15th June 2023, Auburn, AL, USA.

Figure 1. Action of Senvelgo (Velagliflozin)

Figure 2. Practical use of Senvelgo (Velagliflozin) for Practitioners