VETgirl On The Run
What's New with Feline Diabetes with Dr. Ellen Behrend, PhD, DACVIM
Today's spec goal podcast is sponsored by Boranger Engleheim. Boranger's animal health business provides first-in-class innovation for preventing and treating disease in animals. The company offers a wide range of vaccines, parasite control products, and medicines for pets, courses, and livestock to veterinarians, animal owners, farmers, and governments. As a leader in animal health, Boranger Engleheim values that the help of humans and animals is deeply connected and strives to make a difference for people, animals, and society. Learn more at boranger-engleheim.com/animal-health. Hi, Vekro here today, and really excited to be interviewing Dr. Ellen Barron, who's a board-certified internist, and today, we're going to be talking about feline diabetes. I always feel like we do more canine podcasts, so really excited to talk about all things cats today. Dr. Barron, thank you so much for joining us. You're welcome. All right, just so our audience knows a little bit about who you are. Do you mind just giving us a little bit of background? Where did you train? What do you do? And what do you do right now? Okay. So I went to Penn Internship at Michigan State, two years in private practice, residency at Colorado State, and then I went to Auburn, where I spent the majority of my career, did my PhD, and I was on clinical faculty there for about 25 years, until three years ago when I left the university, and I am now working full time for veterinary information network. Wonderful. Well, thank you so much for all that you do. You know, I wanted to talk to you today about feline diabetes. I know there's so much coming down the pipe and new things that are out there, and we always need more help, right, when it comes to treating our feline endocrine patients. So I wanted to ask you about what's new. Do you mind telling us a little bit more about the new class of drugs for treating feline diabetes, sodium glucose co-transporter two inhibitors, which we're just going to call SGLT 2i from now on? How do they work and what do they do? Perfect. So I'm really excited about this new classification of drug. I think they're going to be an absolute game changer. I think they already are being an absolute game changer for feline diabetes. So SGLTs are a group of proteins that move glucose across membranes, and we're most interested in SGLT 1 and 2 for this talk. SGLT 2 is present in the renal proximal tubule, and its job is to move sodium and glucose. It's a co-transporter out of the tubule lumen and reabsorb them back into the blood circulation. And SGLT 2 normally reabsorbs 90% of the glucose that's in urine. SGLT 2i are a group of drugs, and they're called the glyphizins, which can be pronounced multiple different ways. I will say I say glyphizin, so there's velliglyphizin and bexiglyphizin. That's syvilgo and bexicat in veterinary medicine, but there's lots of other glyphizins out there. They're available in humans since 2013 for treating type 2 diabetes, and they have totally revolutionized human diabetes treatment. So if you give an SGLT 2 inhibitor and block SGLT 2, then you prevent the reabsorption of glucose from the renal tubule. So there's going to be lots of glucose excreted in the urine, and that's basically how they work to get blood glucose down in diabetics, they prevent the reabsorption of glucose from the urine. That function is independent of insulin, which is, I'm going to probably going to mention that in a few times because that's an important thing to know and to understand. So they work independent of insulin, but insulin is still needed. So these are licensed for cats with endogenous insulin because insulin is still needed to prevent diabetic ketoacidosis. And that's a problem, a complication, a consideration. That's the best word for using SGLT 2i. The other really important thing to know in general about SGLT 2i is that the risk of hypoglycemia is really, really, really low. It's not impossible. I've heard of a couple cats now that became hypoglycemic, but it's really low. That was the best explanation that I've ever heard of that drug. Thank you so much. Okay. That's super concise. I absolutely love it. Clinically relevant. So that was fantastic. You know, it's interesting because by the time I see them as a critic list, they're a DKA. They're flat. They're dehydrated. They're hypovolemic. They have no endogenous insulin, right? And so in that scenario, it is really interesting that you brought that up. So to confirm every single day, general practitioners hear from their pet owners or cat owners, isn't there anything oral I can give? So for once, there's something oral. Now, do you mind talking about how effective SGLT 2i's are for treating cats with diabetes? And can we use them in dogs? So I'll do the dogs first before I forget and go off on a tangent or off on a whole diatribe about cats because I think these drugs are great. We can't really use them in dogs and they're not licensed for dogs. So remember that cats and dogs are different in their diabetes. Dogs are type 1 diabetics, which means they're insulin deficient. And with insulin deficiency and an SGLT 2i, you're asking for diabetic ketoacidosis. So they're not going to be used alone ever in a dog. We'll never say never, but you know, not really. With cats, they are mainly type 2 diabetics. So the vast majority of cats, at least to start, still have endogenous insulin. They don't have enough to maintain blood glucose, but they still have some. And that's going to be what is going to prevent the DKA when we start an SGLT 2 inhibitor. So off the table alone in dogs. In cats, they are hugely effective. They're not the magic bullet. There is no magic bullet for diabetes, unfortunately, as much as we would love to find one. Now I'm going to be talking more about San Valgo than Bexacat, because full disclaimer, I am a paid consultant for San Valgo for BI. That has never stopped me from giving my own opinion, though. But because I am a paid consultant, I know more about the data behind San Valgo than I do about Bexacat. I've seen the publication on Bexacat, but I don't have all the data like I do for San Valgo. If you consider San Valgo and Bexacat equivalent for the most part, San Valgo is a liquid that is dose based on a milligram per kilogram basis. Bexacat is a pill that is one pill per cat for any cat over 3.3 kilograms. Other than that, until we have evidence that they're different, I'm going to think about them in the same way. So taking a look at the San Valgo data, there was 180-day study in this country to get licensed sentencing. And two thirds of the cats finished the 180-day study and did well. Some cats got kicked out for reasons unrelated to the drug. Some of them were just the owners weren't being compliant. Some cats didn't respond small percentage, but it's possible. And some cats did get kicked out for reasons related to San Valgo like they went into DKA. But overall, two thirds of the cats basically stayed in the study for the full 180 days and were doing great at the end, which I don't think we see with insulin. I just think that's amazing. Blood glucose and fructoseamine were in the reference interval in about 60% of cats, 55 to 60% of cats at day 30, 80% by day 180, which again, I think is absolutely amazing. We don't get normal blood glucose and fructose amines in insulin like we do with an SGLT2 inhibitor. Blood glucose curves are flat in cats on SGLT2 inhibitors. We don't have the ups and downs and sometimes it's really high and sometimes it goes low and all the variation that we do with insulin. So that's a huge advantage with these drugs. Talking about clinical signs, PUPD improved in already about a third of cats on day two, three of getting this drug, like they can respond really quickly, 50% improvement by day seven, and about 90% had improved by day 180. That was as judged by the owner, but really high numbers. The improvement in polyfasia was pretty similar, not quite as good. The improvement day two, three was probably more like 25% and day 180 was more like 70%, but still really impressive numbers. Well, aren't all cats polyfasia? No, just kidding. That's another podcast. That's great to hear. Mine aren't. Right? Mine three are. Or I will admit it. Exactly. And you know, it's interesting because as veterinary professionals, we probably noticed the severity of PUPD more because we're like, hopefully, neurotically scooping and actually looking at the clump size. So for a head owner to notice this or a cat owner to notice this, that's quite significant. Now, are there any adverse effects of these drugs and how common are they? Well, of course there's adverse effects. I don't know of a drug that doesn't have an adverse effect. Do you? No, it doesn't happen. So the number one adverse effect in the study on Cinvelgo was if you read the detailer or the FDA Freedom of Information Act says 50%, that sounds really scary. I don't think it's as bad as it sounds for a couple of reasons. One is that diarrhea was an FDA mandated term. So that means it could have been anything from a slight softening in the stool to hugely watery diarrhea. And the other thing is that the owners were told to check the stool and report on it every day. Well, how many owners really do that if they're, you know, if they're just scooping the litter really quickly. So soft changes in stool could have been reported that the owner never would have thought anything of unless they were in the study. The diarrhea, if it happens, does typically happen pretty soon after being put on the drug. It's usually self-limiting and it's usually mild. So again, I don't think it's that big a deal. There weren't two cats that were kicked out of the study because the diarrhea was so bad the owners couldn't take it. So it's possible, but I don't think it's a very common thing at all. Only two cats out of 200 and I can't remember now, 42 or 52 cats that were in the study. So pretty small number. It was the number two, diarrhea was the number two clinical sign on Bexacat. And I don't think that's really a real difference. I just think that's luck. Vomiting was the number one clinical sign or adverse effect in the Bexacat study. And in the Sivelago study, it was number two. And I think that was just luck, random, not very often, no cat got kicked out of the study because of that. I mean, like if you're giving an oral drug to a cat, of course, you think it's vomiting. So not really surprising. We need to take DKA seriously. DKA can kill cats, as you well know, as a criticalist. It can be bad. It is bad when it happens. But I think the way that Bexacat was released made it sound like every other cat was going into DKA and you had to be really cautious and really worried. You do have to select your cats appropriately. There are some cats that are not good candidates. But overall, the incidence of DKA in the Sivelago study was 7%. The incidence of ketosis, cats having gettinuria, but not going on to DKA was also about 7%. So that's probably pretty comparable to what it is with insulin. I mean, diabetic cats can go into DKA. A couple things to know about the DKA with SGLT2 inhibitors is, one, it typically happened in the first two weeks. So that's the period that we're watching the cats most closely. Eighty-five percent of the cats that had either ketosis or DKA did so in the first really ten days of the study. The other thing is that this is a slightly different form of DKA. We are used to diabetic cats or dogs that have DKA to have blood glucose that are really high, 400, 500, 600 when they come in and DKA. Because of the way SGLT2 inhibitors work, these cats are typically euglycemic DKA, meaning that their blood glucose is less than 250, even though they're in DKA. So I think in cats on insulin, if it's sick, but it's blood glucose is not 400, 500, 600, people don't think about DKA. Like if the blood glucose was 200, they would be like, "And this is not DKA." With the SGLT2 inhibitor, we need to redefine the way we think about it. Any sick cat on an SGLT2 inhibitor, no matter what its blood glucose is, could be DKA. And then you have to check for it. One other thing, a couple other things I want to mention about adverse effects, people ask all the time, and I think it's a great question about whether or not this is going to increase the risk of urinary tract infections. That's a really difficult question to answer in people. And the answer is probably not or maybe slightly increases the chance of cystitis. And the guess is that's because it is putting glucose into the urine in people. So that's a great growth medium. Again, in people we really don't know. In cats, we don't know either. The studies that have been done so far were not designed to look at that. My guess is it really won't make a difference because most diabetic cats have glucose urea anyway. Even when they're on insulin, they have glucose in their urine, a good part, if not most of the day. People get put on SGLT2 inhibitors before they have glucose urea for various reasons. But then when you increase, you put glucose in the urine, then I think you can increase the risk of urinary tract infection. Since cats pretty much always have glucose in the urine when they're a diabetic, I don't think putting more glucose in the urine is going to make a difference, but that's just my best guess though. That is great information. I always joke when we have that sick diabetic cat or that sick cat that comes in really hyperglycemic. When you check it on a glucometer, it always flashes check ketones, check ketones. It's good to know that with the SGLT2 inhibitors that even if they have a sick cat, the blood glucose is only 200 that we should be checking for ketone urea, so great, great point. That brings me up to the next point. What would you consider a good candidate for using a SGLT2 inhibitor? Obviously, it's not the type that I'm going to see in the ER ICL. The cat that is coming in for the first time as a diabetic and DKA is not the cat you're going to use an SGLT2 inhibitor. Basically, we're looking for a happy cat, so a cat that is eating well, drinking well, urinating well, and is basically a happy cat despite the fact that it's a diabetic. If it's lethargic, vomiting, has diarrhea, has active pancreatitis, and we could talk for three hours about how you define active pancreatitis. It's dehydrated or it's caectic. Those are cats that you're not going to use an SGLT2 inhibitor. I will say also that SGLT2 inhibitors are only indicated per the FDA for naive diabetics, so a cat that has been on insulin before, if you put it on an SGLT2 inhibitor, that is off-label use. As far as renal function goes, the label says that any cat that has a creatinine greater than two should not be started on an SGLT2 inhibitor, and that's mainly because, at least in the Sinvelgo study, cats with the creatinine greater than two were not allowed in the study, so it's not that we know that a cat with a creatinine greater than two does poorly. We don't know, there were a couple cats in the Sinvelgo study that were moved due to a progressive asotemia, so there could be some effects on the kidney, for sure, not very common, but there could be some effects on the kidneys. I don't measure FPL. There are guidelines about that, more so for Bexacat than for Sinvelgo. If a cat is happy, is eating, is drinking, is not vomiting, doesn't have diarrhea, personally, I don't care what the FPL is. It does not have clinical pancreatitis, and I'm going to try an SGLT2 inhibitor anyway, so why even bother measuring it? Urinary tract infections, you know, cats obviously that are diabetic can have urinary tract infections. Wonderful, thank you so much. You know, I hope you don't mind me asking you this question because I know general practitioners would probably be asking the same thing too. Okay, so you have a cat, it comes in PUPD, you diagnose it as a naive diabetic, the owner says, "I don't want to do insulin, I can't do insulin, I can't afford it, I don't want something oral, would you be able to start that naive cat on just an SGLT2 inhibitor without insulin therapy, and nutritional management and weight loss and all that?" Yeah, so that, I mean, yes, you can do it, you're not supposed to use it within insulin, it's supposed to be a standalone therapy, so for an naive diabetic cat that comes in that is a happy, healthy diabetic, I would try an SGLT2 inhibitor, even if the owners were willing to do insulin, like, I have three cats that are fat, I will say that, and if any of them become diabetic and they're happy, healthy diabetics, I'm trying SGLT2 inhibitor first because I think these are such great drugs. How much diet plays into SGLT2 inhibitors, who knows? There actually, some people think that you should not use a low carbohydrate, high fat, high protein, the typical feline diabetic diet in combination with an SGLT2 inhibitor, because in people, low carbohydrates increase the risk of DKA if they're on an SGLT2 inhibitor. I still recommend a diet change because I think by itself, it can have such great effects on getting diabetic control and inducing remission and keeping the cat in remission. Cats are not small people, cats metabolize carbohydrates so differently, that until we have evidence that it's bad in cats, I'm still recommending the diet in combination with the SGLT2 inhibitor. I would change the diet like two or four weeks after being on the SGLT2 inhibitor, because both of those things, starting the SGLT2i and changing the diet can cause diarrhea. So, I would use the SGLT2i and then when things are going okay, then change the diet. That's a great suggestion, right? Like, as an internist, never change things quickly. Take one thing at a time. Now we want to know what cause wants or do you think they're done? Exactly. And for our non-North American listeners, a grantee of two makes for desk leaders approximately 177 millimoles per liter, just so you know. All right, so we talked about clinical science, we talked about rare adverse effects, we talked about the naive diabetic, we talked about the candidate, talked to me about monitoring. What are your recommendations for monitoring cats that are on an SGLT2 inhibitor? Great question, and you know, we're all still on a learning curve with SGLT2i's and cats, so ask me again in six months. I mean, I've already changed my answers to some of these questions over the last six months of gaining experience, so we're on a learning curve. So, I think the monitoring is going to be significantly less in the long term and cats on SGLT2 inhibitors. And I think curves, and I use curves to mean like in clinic curves, in home curves, putting a Libra on a cat, all of that where you're like measuring glucose over time, I think those are going to mainly be a thing of the past. So, I think where these drugs are going to be so much more helpful besides the fact that owners, okay, there's a few ways, I just kind of say this, there's a few ways where these drugs are going to be really helpful. One is oral versus injections, and although, personally, I think injectable drugs can be a lot easier in some cats. Injections freak owners out. These drugs, both of them, Bexacat and Sinvelgo, can be mixed with a little bit of food and the cat can eat it, so it's easier to give. Both are once a day. The time of day doesn't really matter. I mean, it should be consistently about every 24 hours, but whether you give it 10 AM, 2 PM, 9 PM, I mean, who cares? It really doesn't matter, and you don't have to pair it with food. So, you know, whether you have to pair meals and insulin, especially you cats can be somewhat controversial, I still recommend doing that with an SGLT2 inhibitor, as long as the cat is eating well, it doesn't matter. Let the cat eat how it wants meal feed, graze, whatever, and give it the once a day medication when you want, and that's just going to make it so much easier. So, that's multiple ways that these drugs are going to be so much easier, but another way is that the monitoring, I think, is going to be much simpler. So, in the first month, we're going to be monitoring them more carefully, and especially in the first two weeks, we're monitoring them more carefully for ketones, because again, DKA is more common in the first two weeks, 85% of cats in the study went into DKA or ketosis in the first two weeks. So, day two or three, they should be checked for ketones, whether that should be urine monitoring or blood monitoring, that's like another whole half-hour discussion, but you should check for ketones in some way on day two or three, and I will also say if you're using blood monitoring, which I think I prefer, but if you're using blood monitoring in clinic, then the precision extra is the ketone meter that is recommended, because that's the only one that's been validated in cats. Day seven, I would check ketones, check in with how the cats do in clinical signs-wise, do a physical exam and wait, do that on day 14, and again on day 28. So, assuming the cat's doing well the whole way through, just kind of keep checking up on the cat throughout that time. Day 28 for sure, I would do a fructoseamine level, probably I would do one on day 14. I think fructoseamine is going to be the way that what we monitor these cats long term. One thing to understand about me is that I am a control freak, so I would really like to have like a Libra put on the cat on day 28 as a baseline for comparison later in case we have some questions about how good control is, to make sure that the cat really does have much better blood glucose and the owners are not just seeing a placebo effect. That may be more than is necessary, and again I may change my mind over time, but right now I would really like to see a curve of some kind day 28. If the owners can't afford it, if it's not possible, clinical signs are under control and fructoseamine looks good. I think you can be assured that the cat is doing well and can continue. After day 30, day 28, day 30, if the cat's doing well I would check in again day 90. At that point, physical exam checking on the control which to me is going to be fructoseamine and check the weight to see how the cat is doing as well. Some people recommend checking ketones day 90 and you know every time you check the cat after that, personally I wouldn't. I mean if the cat's doing great, I don't know that measuring ketones is going to be very helpful. Quite honestly right now, I think that interpreting ketones when a cat is happy and healthy and eating well and drinking and not vomiting is one of the biggest places that I struggle with in using an SGLT2i because we see cats with elevated ketones or ketonuria and they're happy. They're not acting like they're in DKA, so what does that mean for that cat? We don't know at this point, we just don't know. So after day 30, if they're happy and healthy, I don't think I'd measure ketones because if it's high, I wouldn't know what to do with it. So I'm just going to probably ignore the number anyway and then probably check them about every 90 days. And again, fructoseamine is going to be my main way of checking them and I would be looking for a number in the reference range. With cats on insulin, we typically want fructoseamine to be in the upper part of the reference range or slightly above. Because of how well SGLT2 inhibitors control blood glucose, I would now be aiming ideally, and you might not get it, but I would be aiming ideally for a fructoseamine in the reference range. Such great information. I wish joke, if it ain't broke, don't fix it. All right, don't change anything. There are tough results are not going to change anything. Exactly. On the test. Although truly that is the difference between criticalist and internist sometimes. Awesome. Awesome information. You know, it's so great to know just from what you're saying, like the owner compliance is going to be so much better for cat owners. They're just so intimidated by the insulin syringe. You know, and I can't blame them, even if you have them practice in front of you, once they're used to it, they're used to it. But I'm always amazed owners will run home from happy hour. They'll be like, I'll have to get this insulin into my cat. And like, it's like approximately every 12 hours, not exactly every 12 hours. That's even more true with an SGLT2 inhibitor. You know, it really does not have to be every 24 hours. You know, if they're off by three or four hours on either side, because the effective SGLT2 inhibitors are going to last for longer than 24 hours. Actually, if you have to stop an SGLT2 inhibitor, they continue to work typically for a day or two. So if you're late, if you have to miss a day because you're out of town, quite honestly, I don't think that's a big deal. I like the way you practice. Love it. I try to be practical and, you know, use common sense. Exactly. And again, that was like the best shortest patho fizz explanation about the drug work. I absolutely love it. Dr. Barron, thank you so much for all that you do. Really appreciate it. And just so, so excited that there's a new option for cat owners when it comes to treating diabetes. Thank you so much. Absolutely. You're welcome. Happy to be here. Important safety information. Sanvelgo, the loglificin oral solution, is for use in cats only, and is indicated to improve glycemic control and otherwise healthy cats with diabetes mellitus, not previously treated with insulin. Before using this product, it is important to read the entire product insert, including the boxed warning. Cats treated with Sanvelgo may be at an increased risk of diabetic ketoacidosis or a euglycemic diabetic ketoacidosis, both of which may result in death. Development of these conditions should be treated promptly, including insulin administration and discontinuation of Sanvelgo. Do not use Sanvelgo and cats with diabetes mellitus who have previously been treated with insulin, who are receiving insulin or in cats with insulin dependent diabetes mellitus. For more information, please see full prescribing information. [Music]