Oral cat anti-diabetic Velagliflozin (Senvelgo)

RE: Oral cat anti-diabetic Velagliflozin (Senvelgo)

Anthony Dennison — Mon, 11 Dec 2023 09:58:22 GMT

One of our vet's cat was diagnosed with DM the same week I found out about Senvelgo at LVS - we've put him on it, and seems to be doing well. Last week I had a little old lady, bent double with arthritis, present a cat who also turned out to have DM so I decided to use this for improved compliance as she would struggle injecting twice daily.

I think the part about 'do not switch cats stable on injectable insulin' part is for clients that have diabetic cats and then read about Senvelgo and want to swap for an easier life, it would probably mess things up for a while.

RE: Oral cat anti-diabetic Velagliflozin (Senvelgo)

Rob Loxley — Sun, 10 Dec 2023 17:05:02 GMT

[quote userid="7002" url="~/f/clinical-questions/30750/oral-cat-anti-diabetic-velagliflozin-senvelgo/243172#243172"]Can anyone tell me what strips/ketone meter they are using to measure BHB please[/quote]

We use the Bayer ketodiastix for urine (or multistix 10SG); looking at a https://www.glucorx.co.uk/shop/glucorx-hct-meter/ but not sure, especially as it seems you want to check for ketones regularly post diagnosis which is likely getting the owner to test urine. Apparently the blood testing is more sensitive but the data for stopping senvelgo is based on uriene ketone, so you might stop some that would subsequently stabalise (IIRC)

RE: Oral cat anti-diabetic Velagliflozin (Senvelgo)

Sara Ramsey — Sat, 09 Dec 2023 18:38:12 GMT

I am curious with this too. The marketing states 10% of cats are euthanased at diagnosis because insulin treatment is not possible.

This might stop some of those cases?

Can anyone tell me what strips/ketone meter they are using to measure BHB please.

We don't have a way to do this but have an EPOC and dipsticks obviously!

The rep is coming to see us in January..she is pretty busy!

RE: Oral cat anti-diabetic Velagliflozin (Senvelgo)

Mellora Sharman — Thu, 31 Aug 2023 15:45:34 GMT

As you say - it will be interesting to see more data and larger case studies using this drug. I don't believe any head-to-head comparisons have been made with insulin, not that it is being marketed in such a way to suggest it will lead to remission as well as other available options.

But, as beta cell exhaustion is related to a need to excessively excrete insulin in order to maintain glucose uptake. A drug like the STGL2 inhibitors lowers blood glucose by increasing renal excretion - thus lowering demand in B-cells and helping to improve dysfunction / exhaustion. So it does offer a good alternative, especially for owners that may be unable or unwilling to use insulin.

I'm certainly keen to see data from available studies, and see how things pan out with this option.

RE: Oral cat anti-diabetic Velagliflozin (Senvelgo)

Kate Richardson — Thu, 31 Aug 2023 15:39:19 GMT

But if they have beta cell exhaustion, they can't produce enough insulin. My gut feeling is this won't lead to remission as often as good control with insulin does. I'm not convinced by it, but will wait and see. To be fair I have only skim read the information so far!! I just feel it increases the risks of ketoacidosis as well

RE: Oral cat anti-diabetic Velagliflozin (Senvelgo)

Mellora Sharman — Thu, 31 Aug 2023 15:01:17 GMT

The STGL2 inhibitors act by preventing renal reabsorption of glucose in the kidneys and thereby increasing urinary excretion of glucose and lowering blood glucose.

So you're right that there is no direct effect via insulin-derived mechanisms. However many cats are type II diabetics, and do not have insulin-dependent diabetes mellitus (see the linked ALIVE statement above) but as a simple explanation - they rather have B-cell dysfunction or insulin resistance. Lowering BG by excreting more glucose and/or whilst managing comorbidities that contribute to insulin resistance could aid remission without the need for insulin therapy in some cases - or at least this would be my understanding of using this type of agent as an alternative to insulin therapy.

RE: Oral cat anti-diabetic Velagliflozin (Senvelgo)

Kate Richardson — Thu, 31 Aug 2023 13:27:36 GMT

What I don't get, is how are the cells supposed to uptake glucose into them without additional insulin? All very well excreting more glucose but the body still needs insulin? Or am I being stupid

RE: Oral cat anti-diabetic Velagliflozin (Senvelgo)

Mellora Sharman — Sat, 26 Aug 2023 09:50:06 GMT

Yes, in terms of an option for oral therapy, however the mechanism of action of this new agent is different to glipizide.

Glipizide is a sulfonylurea - which stimulates insulin secretion from pancreatic B-cells - might improve signs in some cats, doesn't often result in diabetic remission and can end up with a progression to a need for insulin after several years anyway.

The STGL2 inhibitors act by preventing renal reabsorption of glucose in the kidneys and thereby increasing urinary excretion of glucose in order to lower blood glucose. Certainly some of the studies look encouraging for better improvement in glycaemic control than perhaps was achievable with glipizide.

RE: Oral cat anti-diabetic Velagliflozin (Senvelgo)

Mellora Sharman — Sat, 26 Aug 2023 09:41:37 GMT

I believe bexagliflozin is also an STGL2 inhibitor as is this new product, yes.

It is good to have options!

Have you tried FreeStyle Libre's on your patients for glycaemic monitoring?

RE: Oral cat anti-diabetic Velagliflozin (Senvelgo)

Rob Loxley — Sat, 26 Aug 2023 06:48:18 GMT

[quote userid="10320" url="~/f/clinical-questions/30750/oral-cat-anti-diabetic-velagliflozin-senvelgo/242225#242225"]like you say, oral may actually be more difficult than injection for some owners, but it's nice to have options on the horizon[/quote]

makes me think of glipizide?

RE: Oral cat anti-diabetic Velagliflozin (Senvelgo)

Lucy Fleming — Fri, 25 Aug 2023 13:50:45 GMT

Ah, perhaps it was just the urine dipsticks I was thinking of (and to be fair, I think it was mainly me misremembering comments from US-based vets about Bexacat/ bexagliflozin, though the agents seem similar).

They certainly seem like interesting alternatives - like you say, oral may actually be more difficult than injection for some owners, but it's nice to have options on the horizon. I'm often fairly loose in my glycaemic monitoring in feline diabetic patients (I've yet to find a truly practical and useful method for most) but I'd certainly hope to be significantly improving more than one clinical sign!

RE: Oral cat anti-diabetic Velagliflozin (Senvelgo)

Mellora Sharman — Fri, 25 Aug 2023 09:11:29 GMT

Hi Lucy,

The following article by the ALIVE project might be helpful in defining some aspects of insulin dependent vs insulin resistant DM in cats (https://www.sciencedirect.com/science/article/pii/S1090023322001253); although it may remain a challenge to define - and exclusion of other causes might remain our mainstay. We can measure insulin, although there might be some overlap between groups.

In terms of measuring ketones - urine dipsticks using the nitroprusside methodology typically document acetoacetic in the urine (or blood), but not acetone or BHB. In acute DKA, the concentration of BHB to other ketones rises due to this being the dominant ketone in this scenario - so test strips using a nitroprusside reaction (ie urine dipsticks) can result in lower detection rates of ketones in blood or plasma. Test strips that measure BHB in blood or urine are more ideal to detect DKA.

Similarly we can see urine ketones become negative during treatment as acetoacetate is cleared, but these patients may have persistent increases in BHB and therefore still technically be in DKA, despite a negative urine glucose using the nitroprusside reaction. But overall BHB tends to be our more helpful test strip in DKA scenarios.

Hope this helps - I'm keen to hear a bit more about this new agent. The studies reported so far seem to suggest 'non-inferiority' (not superiority) to insulin administration. And I'm not entirely convinced that giving an oral agent is easier for cat owners than injections albeit SID therapy might be helpful here. But I'd need to see the data in a bit more detail than I believe is currently available.

In the clinical field trial mentioned in the licensing SPC document: The composite variable “treatment success” was comprised of an improvement in at least one clinical sign related to diabetes mellitus (polyuria, polydipsia, unintended weight loss, polyphagia, or diabetic neuropathy) and improvement in at least one glycaemic variable in comparison to the screening visit.

The glycaemic variables were a BG of < 17 mmol/L, or fructosamine of < 450 umol/L (and lower than the screening value). I don't know the absolute values that were achieved by the cats without further digging which overall still seems pretty loose potentially, although 87% of cats were considered to have good, very good or excellent glycaemic control overall. I'd be keen to look at their definition of good, very good etc.. But perhaps most cats had values way better than those cut-offs mentioned.

I don't see more information from the field studies mentioned outside of the licensing information (unless I have missed it somewhere) - so I can't see that these studies have been published, or the data made more available as of yet.

Best WIshes,
Mellora

RE: Oral cat anti-diabetic Velagliflozin (Senvelgo)

Lucy Fleming — Thu, 24 Aug 2023 13:56:30 GMT

Sounds intriguing, but not perhaps the panacea we might hope:

"Cats treated with SENVELGO may be at an increased risk of diabetic ketoacidosis or euglycemic diabetic ketoacidosis, both of which may result in death. Development of these conditions should be treated promptly, including discontinuation of SENVELGO and initiation of insulin therapy.

Do not use SENVELGO in cats with diabetes mellitus who have previously been treated with insulin, who are receiving insulin, or in cats with insulin-dependent diabetes mellitus. The use of SENVELGO in cats with insulin-dependent diabetes mellitus, or the withdrawal of insulin and initiation of SENVELGO, is associated with an increased risk of diabetic ketoacidosis or euglycemic diabetic ketoacidosis and death.
Sudden onset of hyporexia/anorexia, lethargy, dehydration, or weight loss in cats receiving SENVELGO should prompt immediate discontinuation of SENVELGO and assessment for diabetic ketoacidosis, regardless of blood glucose level. SENVELGO should not be initiated in cats with ketonuria, ketonemia, pancreatitis, anorexia, dehydration, or lethargy at the time of diagnosis of diabetes mellitus, as it may indicate the presence of other concurrent disease and increase the risk of diabetic ketoacidosis."

How do we even really know whether a cat is an insulin dependent or non-insulin dependent diabetic? I believe they require a particular type of ketone meter as well, not just the standard BHB one most clinics have knocking around.

RE: Oral cat anti-diabetic Velagliflozin (Senvelgo)

Arlo Guthrie — Fri, 18 Aug 2023 17:36:31 GMT

Thanks Martin … reason I haven‘t yet reported it is because Boehringer hasn’t yet sent me a press release about Svengali for cats, and I’ll bet that’s why VT hasn’t yet published anything either.