Speaker 1:

Welcome to AACE Podcasts. Thanks for tuning in as we elevate clinical endocrinology by taking deep dives into trends and topics that can help us improve our patient care and global health. Find the latest episodes on aace.com/podcasts. And now let's meet the endocrine experts who will be talking with us today.

Vin Tangpricha:

Hello and welcome to this AACE podcast. My name is Vin Tangpricha. I'm the host of today's podcast and I'm also the editor-in-chief of AACE's official journal, Endocrine Practice. Today we have special guest, Dr. Rifka Schulman-Rosenbaum. She has written a paper on SGLT-2 inhibitor use in the hospital, and she published her article in the December issue of Endocrine Practice, and we have her today to discuss about her paper. I think it was online in December actually.

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Yeah, I think it was. I was going to say, I think it was online in December, but it was-

Vin Tangpricha:

Looks like April 2024.

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Was it April?

Vin Tangpricha:

Yes. So it was published online in December and now it's April 2024 issue. So thank you Rifka for joining us. Can you introduce yourself and let us know what you do at your institution and the roles you hold at AACE?

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Sure. Thank you Dr. Tangpricha for inviting me today. I'm really excited to talk about this article on this topic. As you mentioned, I'm Rifka Schulman-Rosenbaum, and I am the director of inpatient diabetes at Long Island Jewish Medical Center, which is one of the tertiary centers for Northwell Health based in New York. And I'm also a professor at the Zucker School of Medicine at my institution. I'm very involved with AACE and currently serving as the chair elect for the annual meeting. So shout out for coming to our really excellent program in Orlando, May of 2025.

Vin Tangpricha:

Great. I'm going to be there for sure.

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Excellent.

Vin Tangpricha:

So I understand you teach fellows, residents and medical students in diabetes.

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Yes, I definitely do that. I am a clinical endocrinologist, so I see patients actively every day. I do mostly inpatient, but a little bit of outpatient as well. And I run our service in our hospital, which includes inpatient diabetes and also other inpatient endocrine topics. And I have a multidisciplinary team, which includes nurse practitioners, diabetes educators, pharmacists, as well as our fellows, residents, and students that rotate through. We have a really busy service. We see a lot of patients. We also have at our hospital, we are joint commission certified for advanced inpatient diabetes, so we're a diabetes center of excellence.

Vin Tangpricha:

So it sounds like you are maybe, can I call you an endo hospitalist?

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Yeah, sure. I've heard that term thrown around and either inpatient endocrinologist or endocrine hospitalist for sure.

Vin Tangpricha:

So that's definitely a field that's growing within our own field. So you have a lot of expertise in management of inpatient diabetes, I assume?

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Yes. So I published a book called Diabetes Management in Hospitalized Patients: A Comprehensive Clinical Guide. It came out in January of this year, 2024. I'm the editor and there are many excellent chapters from authors all over the country on every topic imaginable for inpatient diabetes.

Vin Tangpricha:

Looks very thick.

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

It is thick. Took a lot of work.

Vin Tangpricha:

So this is a field that's been rapidly evolving. I mean, when I was a fellow, inpatient diabetes was basically insulin and trying to tell people not to use sliding scale. Now it's more than that, I understand.

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Yeah, it's really grown so much. And from what you're saying, I recall also as a resident where you didn't really focus too much about diabetes in the hospital. Patients were continued on oral agents frequently. Sulfonylureas, no problem. Everything has changed so much. Really, the field has really grown so much.

Vin Tangpricha:

So one of the things I hear often from the residents is that, "Oh, we don't want to change their regimen because they're going to be going home in a few days. Just keep it the same." Is that mantra still true?

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

So you mean change what they're on at home or change what they're receiving in the hospital?

Vin Tangpricha:

They come in and they'll just start what they're on at home and no changes are made and they're discharged a few days later.

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

So there may be patients where that is the right move because their A1C is really well controlled, they were doing fine at home, in which case, sure. I mean you can for the most part continue what they're on in the hospital if those medications are appropriate for the hospital, which is a whole separate conversation. But then you have the patients that are not controlled well at home, their A1C could be high or they could be having hypoglycemia all the time. And so this is a touch point where the inpatient endocrine team actually has the opportunity to really help people.

And in my area in New York, there is a lack of appointments for access to outpatient endocrinology. It's at least a six months wait often to get in new as an endocrinology patient. And so this is our opportunity to help patients adjust their regimens. Why do they need to wait another 6 or 12 months to see the endocrinologist in the office if I can help them right now? And so I spend a lot of time not only managing their insulin in the hospital, but also going through their outpatient plan and making sure that we don't need to escalate their regimen, prescribe them a CGM, prescribe them a GLT-1 or SGLT-2 or whatever's appropriate.

Vin Tangpricha:

Yeah, I totally agree. I mean, they're in the hospital, you have all their glucoses, why not make use of the data?

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Absolutely.

Vin Tangpricha:

Well, this is a great segue into SGLT-2 inhibitors. Let's say you have a patient who's well controlled on SGLT-2 inhibitor and they come and get admitted for let's say cellulitis or some other common internal medicine condition. What should we do?

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Well, that is a great question worthy of writing an article or perhaps two articles because as you know, there was kind of a pro and a con series of articles on this topic. And to just give you a little bit of background, our major organizations, including AACE, we focus on using insulin for hospitalized patients as the current standard of care. And that's coming after many studies that kind of show the importance of glycemic control, the importance of moderate glycemic control, not overly controlling them but not under controlling them. And so I think at this point, most hospital providers are understanding that insulin is a basic way to manage diabetes in the hospital. And then in the last few years, some studies had come out regarding DPP-4 inhibitors in the hospital and some positive data came out showing that they may be appropriate for certain subset of patients with mild hyperglycemia.

So not every patient has to be managed with insulin. If it's mild hyperglycemia, which could be someone who's on an oral agent at home, they're in the hospital, they might not need to get insulin. They could receive, for example, Linagliptin was the agent that we added onto our formulary. Now the SGLT-2 question that comes up because, well, if DPP-4s are good for certain patients in the hospital, maybe SGLT-2s are because firstly, this class of drugs has so many benefits in general. So we're using them for our patients, not only for the glucose control, but for benefits with CHF and CAD and CKD and all the other reasons why we're outpatient prescribing SGLT-2 inhibitors. The other nice thing about the class is that they don't cause too much hypoglycemia or really minimal just like DPP-4 inhibitors. So it is a natural question to ask of maybe this would be the next big thing to use for hyperglycemia for milder cases in the hospital.

And that is kind of like the underlying reason why we are having these conversations. And to start off, SGLT-2 inhibitors are a little bit different from DPP-4 inhibitors. And without getting into the nitty-gritty of the mechanisms, there is a well-known side effect of DKA or euglycemic DKA with SGLT-2 inhibitors that we're going to spend a little time talking about. So while in the outpatient setting, euglycemic DKA is relatively rare. We prescribe them all the time. We don't have all of our patients heading to the hospital in euglycemic DKA. And as giving you the perspective of as an outpatient endocrinology doctor, which I do once a week, I do mostly hospital, but for the most part, I prescribe SGLT-2 inhibitors all the time. And I have, let's say one patient that I could think of who did develop euglycemic DKA recently, but most majority of the patients that have not, it is very different from the perspective of an inpatient endocrinologist.

I get consults for SGLT-2-induced DKA or EDKA every single week, at least one if not more. So I think it's important to pay attention to the lens through which you are trying to assess the frequency of the problem, because on the outpatient side, it's very different from the inpatient side. So then why is that? Well, firstly, there are certain risk factors that we know about for SGLT-2-induced DKA or EDKA. Those include fasting, right? Because you have a buildup of ketones or low PO intake or very low carb diet. Also, high stress situations, patients going for surgeries, which is high stress situations. So far, if you may notice all the things that happened in the hospital I've just listed, people come to the hospital, they get made NPO for who knows how long, waiting for procedures or surgeries or because they're sick and vomiting and they can't eat. And a lot of them have procedures and surgeries.

The other thing is insulin is actually protective against DKA. So for some patients who are long-term on insulin plus an SGLT-2, if you remove that insulin, that actually raises the risk of DKA. And unfortunately, a lot of times insulin gets held when they first hit the door to the hospital until endocrine gets called or the primary teams think to order it. So there's that issue as well. And the other thing is the FDA put out recommendations to hold SGLT-2 inhibitors three to four days before any surgery or procedure. And that's to mitigate the risk of DKA or EDKA. So by holding the medicine, usually you're doing okay when you have your procedure. But what about using them in the hospital? And so the patient's made NPO. Do you have three, four days in advance to prepare for the NPO? Absolutely not. We all know the NPOs they come at you really quick. So there's a lot of concern surrounding this issue for patients who are in hospital.

Vin Tangpricha:

It sounds like it also, if you have someone who's not on SGLT-2 inhibitor, you just eliminate that as a potential cause of ketoacidosis because there are many, like you mentioned, there's so many causes of acidosis in the hospital, and if you just have someone not on it, then you can't blame the drug, right?

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Yeah, certainly. I mean, patients are sick. So if this is a drug that has a risk for DKA, metabolic acidosis, if there's another option that we can use that doesn't have those risks, that is definitely something to think about. And we are comfortable using insulin and we're even comfortable for the mild cases using DPP-4 inhibitors. So there has to be a good enough reason to use the SGLT-2 inhibitor to take that risk. And just to expand it a little bit more, SGLT-2s, they can cause some orthostatic hypotension, some hypovolemia issues. And if you have patients who are already possibly having issues with hypotension, dizziness and the risk of falls in the hospital is obviously a big issue. So while the other thing is this is really understudied for the glycemic control aspect, and I'll talk more about that soon. There are definitely studies about CHF, but for using SGLT-2s for inpatient glycemic control, we really don't have data on that.

So you kind of have to extrapolate from the information that we do have. The other thing I wanted to mention is the risk of genital urinary infections. And so while the more common thing would be mycotic infections that are not as serious, but UTIs are possible with SGLT-2 inhibitors and sometimes up to a quarter of hospitalized patients have follies in place. And so having a drug that potentially increases the risk of UTI or patients with indwelling follies, the risk is even higher. So there's a number of different concerns.

Vin Tangpricha:

So let's go back to our hypothetical patient. They come in, they have cellulitis, they have Type 2 diabetes, they're on SGLT-2 inhibitor plus Metformin. What are you changing them to now? They're just going to be in the hospital for a few days for antibiotics and go home.

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

So that would be a good patient for an DPP-4 inhibitor because they're just on... Assuming their A1C is good, right? Because you could have a patient like that with an A1C of 10, in which case they need insulin. They need an upgraded outpatient regimen. But for someone, let's say with an A1C of 6.5, and they're coming in on a Metformin and SGLT-2 and their glucose looks fine on admission, you could manage them with a DPP-4 inhibitor with a correctional scale on the side. Sometimes we even do a little bit of basal insulin with the DPP-4 inhibitor.

Vin Tangpricha:

Stop the Metformin too?

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

I mean, look, in my institution, this is what we do is either we do insulin or we do DPP-4 inhibitors. Again, this is for glycemic control. We can get to talking about CHF in a minute. And I think that's an important differentiating point because the focus of my article was talking about why I would avoid using SGLT-2 inhibitors for managing inpatient hyperglycemia. But glycemic control is a different indication than CHF management. And there have been some pretty strong randomized controlled trials showing support of using SGLT-2s inpatient or close to discharge for heart failure management. And so I'm not speaking against that. I'm talking about glycemic control.

Now, there still are risks of using SGLT-2s for the CHF indication, right? There's still the similar risks that we just talked about, but then at least you know, firstly that there's a goal like that there could be improved heart failure outcomes. So there's a reason to take that risk, but then you have to really risk mitigate. So you need to have some sort of process in place for the hospital, or you should have a process to make sure that patients are started on them for heart failure at the right time. And the right time would be when they're clinically stable, when they're not going for procedures or surgeries, when they're eating and not NPO and all those other factors. So it's actually really complex, and unless you have some hospital protocols or EMR trick that helps this process, it can be really confusing and actually dangerous for providers.

Vin Tangpricha:

So we're kind of talking about someone who comes in the hospital, their A1C is 10 and they're hyperglycemic. No, don't do SGLT-2 inhibitor. Do probably insulin, it sounds like.

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Yeah, that's an insulin.

Vin Tangpricha:

Stop the SGLT-2, probably?

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Well, inpatient for sure. And then depending on the situation, if that patient has an indication for the SGLT-2 and there's no contraindication, then I'll add the insulin, let's say, and resume the SGLT-2 at discharge. Once they go home, they could go back on it if there's no reason to stop it per se.

Vin Tangpricha:

So they come in, they have heart failure, once their heart failure taken care of, maybe do the SGLT-2.

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Yeah, exactly. Start it closer to when they go home because we don't want to have clinical inertia where people that could benefit from an SGLT-2 for their heart failure, maybe that they won't get started on it. So it could get started really close to discharge or at the time of discharge. And there is data from the CHF literature supporting that. And that's why it's kind of cool that our two articles, the pro and the con, they actually don't even disagree with each other because the pro article says you should use SGLT-2 inhibitors in the hospital for heart failure. And the con article says you should not use SGLT-2 inhibitors for glycemic control. So they actually don't truly conflict with each other at all. You can kind of bring it all together.

Vin Tangpricha:

For our audience, there are two companion papers. One is a pro and one's a con. And I think we're all on the same page that unless there's a real reason, don't use the SGLT-2 inhibitor and real reason would be someone who has heart failure. But that is one of my follow-up questions. Has there been a study where someone who is an acute heart failure failure, does SGLT-2 inhibitor help in that situation, not the stable ones that are about to leave the hospital, ones that are acutely with CHF, is there a role for that?

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

I mean, there's been a few studies in the CHF literature. Some of them focused on closer to discharge. Some of them were a little bit earlier in the stay. The interesting thing is not all of them looked at glucose metrics and such. They more focused on heart failure metrics. So I don't have all the glucose and ketone measures and all that for all those articles. But it is interesting to know that the benefits of the SGLT-2 towards the CHF does come pretty quickly. In one of the trials at the 15 day follow-up, they already had improved measures of CHF. And so that would be the reason to consider starting it while they are still hospitalized, but stable to make sure they get the full benefit of the CHF therapy.

But yeah, I mean, we don't have data on the glycemic control indication for using SGLT-2 in the hospital. And because it's not standard of care, we don't have a lot of data on it anyway. And a lot of people will cite numbers from outpatient studies about the risk of DKA and say, "Oh, look how rare DKA is with SGLT-2 for these outpatient studies." But you really can't extrapolate that to inpatient.

Vin Tangpricha:

What about the infection? Do we have any data that's showing that's more increased risk of the myocardic genital infections?

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Yeah, so again, because it hasn't been used regularly, inpatient hasn't been formally studied, we don't have data on that. It's all based on outpatient. So this is all kind of using our best judgment with what we have now. But ideally, there would be trials specifically looking at inpatient SGLT-2 for glycemic control. And the other thing we don't have is for the kidney indication, right? That's the third major FDA indication for SGLT-2s is for CKD with albuminuria. And so we don't have data on using it for the kidney indication in inpatient setting. Really just the CHF is the main thing that we could say.

Vin Tangpricha:

I was also surprised in your paper that SGLT-2 inhibitor was no better than DPP-4 inhibitor. I thought it would've been much better, although you're probably going to tell me no data.

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Well, there was a retrospective study comparing the two, and so there was no significant difference in the glucose metrics. And so if you don't have any benefit of the SGLT-2 over the DPP-4 in controlling the glucose, and you do have some major safety concerns for the SGLT-2 class where DPP-4 inhibitors are really pretty benign and very safe. So we use them for the appropriate patients in the hospital. So there wasn't really a reason to push for trying out the SGLT-2s, but again, lack of data.

Vin Tangpricha:

Yes. What do you think the next big study should... I mean, I don't know if... Are you aware one that's coming out or what should be done next?

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

I think we now have a lot of data on CHF indication for inpatient SGLT-2s. So the thing we would benefit from would be a study on inpatient use of SGLT-2, specifically for glycemic control. That's the thing we don't have.

Vin Tangpricha:

What would that be compared to like basal-bolus or what do you think the comparative would be?

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Yeah, I mean, I should mention that there was one RCT, the DAPA hospital trial that looked at post-cardiac surgery patients compared basal-bolus versus basal-bolus plus an SGLT-2. And there was no difference in the glucose measures. It didn't reduce the insulin requirements. And while there was no outright DKA, there was severe ketosis more frequently in the group with the SGLT-2. And one thing about that study is that these patients were heavily insulinized because of their post-cardiac surgery. So they were on insulin drips and then they were on full-on basal-bolus plans with the SGLT-2. And insulin is protective against DKA.

In that study, you're comparing basal-bolus versus basal-bolus with SGLT-2. There was severe ketosis but not outright DKA. If you had a study, I'd be curious to know without the full on basal-bolus plan. I guess there was a retrospective study with DPP-4s, but maybe a more like a prospective kind of study comparing the two and really honing in on rates of DKA and NPO and all the kind of risk factors as well as the data on the Foley catheters and the urinary tract infections and all of that.

Vin Tangpricha:

And I guess when you're sick, you're catabolic and you're insulin resistant, so maybe insulin is the way to go.

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Yeah, it works. I mean, as long as you know how to dose it safely, it definitely works.

Vin Tangpricha:

So we're about to run out of time, but if you could summarize to our audience what are the key take-home messages from your paper?

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

So my paper, which is sodium glucose co-transporter-2 inhibitors, should be avoided for the inpatient management of hyperglycemia is the con article in the set of pro-con articles, which focused on the reasons why I would avoid using SGLT-2s for inpatient management for hyperglycemia. The main kind of focus of the arguments would be the concern regarding DKA, euglycemic DKA, which is a higher risk in the inpatient setting compared to the outpatient related to NPOs, procedures, poor PO intake, holding of home insulin, a lot of risk factors combined with potential risks of urinary tract infections in the setting of Foley catheters and other patients that have urinary issues who are hospitalized as well as orthostatic hypotension. All of these inpatient factors that make me concerned for using SGLT-2s in the hospital.

Also, having seen countless patients with EDKA in the setting of SGLT-2 as an inpatient endocrinologist, that this is actually a really common kind of console. It's a common endocrine console, so any of us who work in the hospital can attest to this is real. This is not a theoretical concern. This is something seeing every day. So until we have better data that might support it, and maybe we never will. I mean, maybe it's just not the right thing to do.

Until then, basal-bolus insulin for the pretty hyperglycemic patients and then consideration for DPP-4 for the mild hyperglycemia patients seems a safer way to go. And just to kind of summarize for the pro article that there is some strong data towards using SGLT-2s inpatient for CHF indication, but once a patient's stabilized and once they're past that higher risk state closer to discharge. So I definitely don't want to discourage that for patients who need heart failure management.

Vin Tangpricha:

Well, thanks so much for writing this article and talking to us today. Do you want to give any shout-outs to your other co-authors?

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

Sure. So Benjamin Cohen, who was my fellow when we wrote the article, who's now an attending endocrinologist in New Jersey. And Yael Tobi Harris, who is an endocrinologist and chief of our division at Northwell Health. They were really helpful and instrumental in writing our article. So thank you guys.

Vin Tangpricha:

Great. I'm glad they all were able to contribute. Thanks so much and I learned so much, and I hope that the audience can continue to learn from you at our annual meetings that are coming up in 2025 and '26. Thank you.

Rifka C. Schulman-Rosenbaum, MD, FACE, FACP:

See you in Orlando.

Vin Tangpricha:

See you there.

Speaker 1:

Thanks for listening to another great AACE podcast. Join us for another episode at aace.com/podcasts and help us in our mission to elevate clinical endocrinology. Together we are AACE.