Veterinary Vertex
Veterinary Vertex is a weekly podcast that takes you behind the scenes of the clinical and research discoveries published in the Journal of the American Veterinary Medical Association (JAVMA) and the American Journal of Veterinary Research (AJVR). Tune in to learn about cutting-edge veterinary research and gain in-depth insights you won’t find anywhere else. Come away with knowledge you can put to use in your own practice – along with a healthy dose of inspiration to remind you what you love about veterinary medicine.
Veterinary Vertex
The Future of Diabetes Mellitus Management in Cats
Unlock the future of feline health with our special guest, Dr. Ellen Behrend, as she unveils the transformative potential of SGLT2 inhibitors for cats navigating the challenges of diabetes mellitus. She focuses on velagliflozin, a once-daily liquid oral SGLT2 inhibitor and brings her passion for endocrinology to the forefront, sharing her insights into this groundbreaking treatment originally successful in human type 2 diabetes. Join us as we dive into this new era of easier diabetes management for your feline friends.
In our engaging discussion, we venture into the evolving landscape of diabetes care in pets, spotlighting novel treatments and their unexpected benefits for renal and cardiac health in cats. Ellen’s personal anecdotes underscore the value of critical thinking and mentorship within veterinary studies, while we demystify common misconceptions about SGLT2 inhibitors, particularly diabetic ketoacidosis risks. Don’t miss Ellen’s article in JAVMA and join us next week for more insightful conversations. Please remember to rate and review us on your favorite podcast platform!
JAVMA open access article: https://doi.org/10.2460/javma.24.03.0174
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You're listening to Veterinary Vertex, a podcast of the AVMA Journals. In this episode, we chat about how a once-daily liquid oral SGLT2 inhibitor is effective as a standalone therapy for feline diabetes with our guest, Ellen Behrens.
Lisa Fortier:Welcome to Veterinary Vertex. I'm Editor-in-Chief Lisa Fortier, and I'm joined by Associate Editor Sarah Wright. Today, we have Ellen joining us talking on the very important topic of feline diabetes. Ellen, thank you so much for being here with us today.
Ellen Behrend:Yeah, absolutely. Excited to be here and thank you for having me.
Sarah Wright:All right, let's dive in to learn more about some new feline diabetes treatment. So, Ellen, your JAVMA article discusses the standalone therapy for feline diabetes mellitus.
Sarah Wright:Please share with our listeners the background on this article.
Ellen Behrend:Well, Velagliflozin is an SGLT2 inhibitor that's the drug classification and they were first approved in 2013 for treatment of type 2 diabetes mellitus in humans and they have completely revolutionized the treatment of type 2 diabetes in humans. Cats, typically, are type 2 diabetics. Their form of diabetes is very similar to type 2 diabetes in humans, so it was logical to try and use this drug classification in cats to see if it could be just as effective
Sarah Wright:Yeah, this is a super important topic
Sarah Wright:I know it can be really frustrating for cat owners that have diabetic cats. Myself actually one of my cats, she's always hyperglycemic. We always have to do a fructosamine and thankfully it's been normal thus far. But we're just keeping an eye on it. Apparently, she's very stressy when she goes into the clinic. But just thank you so much for doing this research.
Ellen Behrend:I actually didn't do the research, I just helped bring it to attention and to get it written up.
Sarah Wright:Well, it's still super important, so thank you. So, what are some of the important take-home messages from this JAVMA article
Ellen Behrend:So, I think there's a number during this podcast. I might mention some off-label use, depending on how the conversation goes, but in general I think it's incredibly important that we have an oral option for cats. Unfortunately, this is not going to be a standalone drug for dogs because of the difference between dog and cat diabetics, but so many people want an oral option for cats. I have heard many veterinarians say that oh, it's so much easier to give an injection to a cat. Why would you ever choose to pill a cat? And that's because we're professionals and you know for us it is easier to give injections.
Ellen Behrend:Typically, for people, giving injections is a huge stress. So this is not the magic bullet for diabetes. Unfortunately there is no magic bullet for diabetes and not every diabetic cat is going to do well on this drug or respond to it very well. But I think we now have a much easier option. It's a once a day, it's oral. There is less monitoring than we typically would do in a cat on insulin. So for the majority of cat owners, I think this is going to be a godsend for treating diabetes.
Lisa Fortier:Hey man, I don't like pilling or injecting cats. That could make it easier. I'm one of those that always seem to get the pills spat back out at me a couple minutes later.
Ellen Behrend:And actually, Velagliflozin is not a pill either. It's a liquid. Bexacat, the other SGLT2 inhibitor that's on the market, is a pill, but Velagliflozin is a liquid, which could be easier or could be harder, depending on the cat.
Lisa Fortier:Sure, depending on the cat. What sparked your research interest in feline diabetes?
Ellen Behrend:Ellen, for whatever reason and I don't know why, I've always been interested in endocrinology. That kind of interests me as a question like why do some people love respiratory and some people love endocrinology? I don't know, just kind of. I think that's the way my brain works. And diabetes is just such a huge issue for cat and dog owners. It is a lifestyle change. It is very stressful.
Ellen Behrend:I had a cat that became diabetic maybe about 15 years ago, so I had already been lecturing about diabetes for a while and was doing research on it in my career and I still found that incredibly stressful. So it's a big area where I think finding options for pet owners to make it not so stressful. I mean, 30% of diabetic dogs and cats are euthanized within a year of diagnosis, based on some of the literature, and a lot of that is because I mean some of that's medical reasons and I'm not judging any owner, but a lot of that is because owners can't handle it financially, emotionally, to be home twice a day to give insulin, et cetera, et cetera. There's a lot of things that go into that decision. So finding something to make it easier and cheaper is a huge need in veterinary medicine.
Lisa Fortier:Yeah, I think all of those things are going to resonate very well with listeners, both as veterinarians and as owners, or everybody knows somebody in this tough situation. Sarah asked you a little bit earlier, Ellen, like what were the key take-home messages? But always when we do research or write manuscripts, we find something that's surprising. What were the most surprising findings when you did this JAVMA article?
Ellen Behrend:Well, quite honestly, it was surprising to me in a way that this drug even worked in cats, even though it was such a big deal in people, because the way that it works is it makes the kidneys excrete a lot more glucose, so you would think that that would make the PUPD much worse. And I remember the first time a student in the classroom asked me about this new classification of drug for people and did I think it was going to be an option in dogs and cats and I was like no, that's a stupid idea. But clearly, it's not a stupid idea and we have experience with oral diabetic drugs in cats and none of them are very good. Besides this new classification, all the previous papers were like, yeah, maybe a third of the cats respond. So the fact that this can be so effective for cats, I think just that in and of itself was really surprising to me.
Ellen Behrend:Um, there are side effects. Not surprising, Every drug has a side effect. I do think that this classification of drug also, um, may be really good for cats with acromegaly and diabetes. According to some research, that's 25% of diabetic cats also have acromegaly. Once they get to the stage of insulin resistance, they are impossible to control, and I think this drug is going to be extremely helpful for them as well.
Lisa Fortier:That's fantastic. I know what you mean about the student suggestions. When I was still an active researcher, I had a whole list of like student resident questions, or participants at conferences give you the best ideas of how you can really change things clinically.
Ellen Behrend:Yeah, true.
Lisa Fortier:So you talked about where we are now and you said there's much more to do. What do you see as the next steps for research in feline diabetes or canine?
Ellen Behrend:I think, still trying to find better ways to control diabetes. Look at the newer insulins, potentially find some other drugs, oral drugs that can help dogs and cats. I think all of those are good ways to go. With the SGLT2 inhibitors, we know in people that they can have hugely beneficial effects on the kidneys and on the heart and there are actually now FDA-approved indications for using these drugs to treat like proteinuric renal disease and non-diabetics. I mean, that's how beneficial they can be. So, I think in veterinary medicine we're going to be hearing a lot more in cats about renal and cardiac effects of these drugs.
Sarah Wright:I also have a proteinuric renal disease, cat too. So I was like ooh, my ears perked up when you said that.
Ellen Behrend:Yeah, I know there's already some research projects on those out there and people are looking.
Lisa Fortier:How many cats do you have right?
Sarah Wright:I have two, but they both have. They have all the things. It's like the vet student curse. You know you got them during vet school, then they have all these weird anomalies and they're the exceptions to the rules, so it's the curse of the vet student cat. Yeah, they definitely keep me on my toes, though, and keep me with my critical thinking in check. So, Ellen, how did your training prepare you to write this manuscript?
Ellen Behrend:I mean, I have a PhD as well as being, you know, having done the residency board certification thing, I don't think you need to have a PhD in order to write a good manuscript.
Ellen Behrend:Of course, that did help me to write this manuscript because I had a lot of experience, but it's really, it's mentorship, having someone who can train you in how to write a scientific manuscript. And, Lisa, I mean you can attest to this. Writing scientifically is a skill just like any other skill. It's like learning to do your first spay, it's like learning to do your first endoscopy. You just you need someone who knows how to do it to show you. And you need good mentorship, showing you where you can go wrong, how to make things better, and then lots of practice. So, I mean, even at the end of my residency, I had great mentorship during my residency. Before I did my PhD, I was able to write a scientific paper. Of course, I've gotten better over the last number of years, but having someone who had done that helped me to write my first few papers is really how I learned.
Lisa Fortier:Yeah, I think one of the things, Ellen, you're absolutely right Like somebody has to constructively guide you on how to do this. And it's one of the things we have worked super hard at the culture for JAVMA and AJVR understanding that many of our authors are first, second, third time authors, maybe one and done. If we want to encourage clinical science, then we really need to help these junior authors and hopefully your team found that in your submission process as well.
Ellen Behrend:Yeah.
Sarah Wright:Yeah, just talking with one of our scientific review board members about this at a conference last week. How do we guide young authors and provide constructive feedback to build them up instead of tearing them down? So, like Lisa said, it's been a culture shift and that's one of my favorite parts about my job actually is working with those young authors and guiding them and serving as a mentor, so I think it's really cool what we're doing. Now, This next set of questions is going to be very important for our listeners. The first one is dealing with the veterinarian's perspective. So, what is one piece of information the veterinarian should know about the standalone therapy for feline diabetes?
Ellen Behrend:Narrowing it down to one, of course, is hard. I think that there is always as there should be, some distrust of new drugs, discomfort with new drugs, and I don't mean like a new antibiotic, because we've been using antibiotics for a long time, but a totally new drug, new classification. I don't know anything about this, so there's a degree of fear that comes with that when you're using a drug that you're not familiar with. Bexaglifazine was the first drug approved in the SGLT2 inhibitor category. When that drug came out, the FDA made a huge deal out of cats dying from DKA and I think that's put a lot of people off this drug category.
Ellen Behrend:Diabetic ketoacidosis is possible in cats on an SGLT2 inhibitor. It may happen more often in a cat on an SGLT2 inhibitor compared to insulin, but in the three papers that are out right now about sole therapy with an SGLT2 inhibitor in diabetic cats two papers on Velaglifazine and one on BEXA the rate was low at 5 to 7 percent. So, the great majority of cats will not develop diabetic ketoacidosis. So, to repeat myself, I think this classification of drug is just a great choice for treatment of feline diabetics.
Lisa Fortier:Ellen, of that 5% or 7% that got ketoacidosis, how many of those died? I didn't know that about the FDA, that they made a big deal about the cats dying. I would presume that not all of that five or seven percent passed away.
Ellen Behrend:So, I think the FDA made a bigger deal out of the DKA than it needed to be. I mean, I get it, DKA is expensive and DKA can kill cats. But I think people came away with the impression that it was really common and it is not all of that, not all that common overall. So, in the Velagliflozin study we had about 14% of cats that had ketonuria or DKA. About half of each. Half had just ketonuria and didn't progress to DKA. Half went into DKA. Of those that went into DKA, 14 did so in the first 14 days of being on the drug and 10 of 14 survived. Four were euthanized. I'm not sure exactly why I didn't have that data available to me but 10 out of 14, so a good bit over 50 percent survived the DKA with treatment.
Sarah Wright:Would you recommend continuous glucose monitoring then, for the initiation of this therapy in those cats?
Ellen Behrend:You know, for the most part we're not recommending continuous glucose monitoring, which makes this a lot easier. So, for the first two weeks of being on the medication and the monitoring recommendations, like the labels between BEXA and Vela are a little bit different, but basically, I approach them the same is to monitor like a day two, three somewhere in there, for ketones only. Day seven, where we're looking at blood glucose concentrations and ketones again, and then day 14, because again that 14-day period is when they're most likely to go into DKA. And then at day 28, check of fructosamine, check for ketones again. Of course we're monitoring clinical signs all along. Whether or not you need to do a curve a day 28, the recommendation is that you really don't need to. I am a control freak, to be totally honest, so I would like to put on a Libre or a continuous glucose monitor to get a baseline after 28 days so that you have it for comparison for later. But that's not a standard recommendation or a standard need, I think, doing curves if you're not quite sure how well the cat's doing, or the cat does well for a while and then becomes PUPD again and you're not sure if it's diabetes coming out of control or it was never fully controlled, or whether something else is causing the PUPD.
Ellen Behrend:I can come up with reasons why to do a curve at different times, but in general, curving and using a glucose monitor is not necessary with these drugs. Fructosamine and clinical signs are going to be the best bets for monitoring control. One reason for that is that with these drugs the chance of hypoglycemia is really really, really low. It's possible. I've consulted on a few cats that became clinically hypoglycemic on an SGLT2 inhibitor, but in general these drugs should not cause hypoglycemia. Those are the rare exception. These drugs should not cause hypoglycemia. So, the need to do curves to try and catch asymptomatic hypoglycemia it's not there.
Sarah Wright:Thank you. I think that's important information for our clinicians listening to have. So now, on the other side of the relationship, what's one thing clients should consider around the standalone therapy for feline diabetes?
Ellen Behrend:Well, again, you know, for someone who's never had a diabetic cat, like they don't know how much better this is. You know, like they don't know what giving insulin twice a day and trying to make sure they're eating specific times and all that like this is like okay, whatever you know. So I certainly don't want owners to think, oh, I'm going to put the cat on this drug and we're good to go and I never need to see my veterinarian again and I don't need to worry about this because there are no side effects and there are no there is no monitoring. That's not true. It is much better than twice a day insulin. It's once a day.
Ellen Behrend:The cats just need to be eating. They don't need to. You don't need to try and pair eating with giving the insulin. They need to be eating, but they can eat when they want, how they want, as much as they want. We're not nearly as concerned about regulating when and how much they eat at each time. And then the monitoring when we're relying on fructosamines and clinical signs. That certainly makes it a lot easier as well. But anytime the cat starts to not act well doesn't eat, is acting off, vomiting, diarrhea, gi signs they need to contact their veterinarian because that could mean they're going into DKA. And again, it happens most often in the first two weeks, but it can still happen at any time. These are diabetic cats. Diabetic cats on insulin can go into DKA at any time. Diabetic cats on an SGLT2 inhibitor can go into DKA at any time. So, they really shouldn't take that lightly, and if the cat seems off, they need to have it checked.
Lisa Fortier:Yeah, thank you for that really important information. I remember one of the anesthesiologists at Cornell used to have an anesthetic protocol called something like the standard dog and the standard cat, and that could never apply to the feline diabetic. There's no such thing.
Ellen Behrend:Absolutely not.
Lisa Fortier:They didn't read the book chapter. I learned a ton from your manuscript, Ellen. Fortunately, I don't have a cat in this situation right now, but thank you to what you and all the other researchers are doing to significantly improve the life of the cats and the owners.
Ellen Behrend:Yeah, absolutely. It was our pleasure to write that manuscript and get the information out there. I mean I have three cats. I'm a cat person always have been. Two of my cats, you know. Going back to what Sarah said about you know the luck of being a veterinarian. Two of our three cats have small cell GI lymphoma. So luckily, they're doing well. But they've been on PRED for years or on and off for years and I live in fear of them becoming diabetic. Had a diabetic cat, as I mentioned before, really would prefer not to repeat that experience if I can and I'll help it. But if they're doing well, they're eating well, they're feeling well, et cetera, and at the time they become diabetic. If they become diabetic, they're going on Valigliflozin or Vexacat, probably Valigliflozin because I think the liquid makes it a little bit easier to give. But they're going on an SGLT2 inhibitor.
Lisa Fortier:Well, fantastic. As we wind down a little bit, we like to ask a little more of a personal question, and what we'd like to know is when Ellen does a puzzle, do you start with the exterior border pieces or do you start with the inside, maybe with a color or a scheme or any other sort of pattern?
Ellen Behrend:The border for sure, in my opinion, that's the only way to do a puzzle like you have to start with the border. Maybe that goes back to my like, how my brain works as an internist, I don't know. But absolutely the border, that's where my mom taught me how to do it. That's, yeah, absolutely.
Lisa Fortier:I have to start asking that did you learn that from somebody?
Lisa Fortier:because we're seeing that most. Maybe it's the PhD part of you, Like they're really. You have to link it together because we find that most of the time the surgeons do the border and internists do the inside and then go to the border. But you have, you're a hybrid.
Ellen Behrend:Wait, say that again. Surgeons typically do the border and internists start internally.
Lisa Fortier:Yes, Well, I guess Most of the time by a color scheme, but not always. We're going to, we're going to collect our data, we're going to go back and collect our data, but we'll have to add in Sarah, we'll have to add in the PhD component.
Ellen Behrend:Yeah
Sarah Wright:Yeah, it's going to be a compounding variable Lisa. For our results so far, we have to go back to everyone's bios and see who has a PhD.
Ellen Behrend:Absolutely, I'm with you. I'm with you. My mom was. I love doing jigsaw puzzles. My mom was a big jigsaw puzzle doer and that's the way she trained me. Never saw a reason to change it.
Lisa Fortier:AVMA, in the different division areas. Some have puzzles there and then people. You know. That's a nice way to again after COVID for people to get together over a coffee and do some pieces. It's pretty fun.
Ellen Behrend:Right.
Sarah Wright:Well, thank you so much, Ellen. We really appreciate you being here today, and just for submitting your manuscript to JAVMA too.
Ellen Behrend:Yeah, thank you very much.
Ellen Behrend:It was fun.
Sarah Wright:And to those listening, you can read Ellen's article on JAVMA. I'm Sarah Wright with Lisa Fortier. Be on the lookout for next week's episode and don't forget to leave us a rating and review on Apple Podcasts or whatever platform you listen to.
