Thank You! | An Update in Glycemic Management in the Hospital: Impact and Lessons from COVID-19

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An Update in Glycemic Management in the Hospital: Impact and Lessons from COVID-19

Jordan Messler, MD, SFHM, FACP | Glytec

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LAURA FLYNN:  I see folks coming in, so we can go ahead and get started.  Welcome, again, and thank you for joining us today.  My name is Laura Flynn, and I am a member of Glytec’s commercial team.  We appreciate you taking the time to be with us today for an update in glycemic management in the hospital – impact and lessons from COVID-19.

Just a few housekeeping items before we jump in.  This webinar is being recorded, and it will be available after today for on-demand viewing.  Second, we will have some time after the presentation for some Q&A.  So at any point, you can add your questions into the Q&A box at the bottom of your screen.  We’ll get through as many as we can in the time that we have, and we’ll be sure to follow up with anyone if we’re unable to answer your questions live.

So I’m now pleased to introduce Dr. Jordan Messler, executive director of clinical practice at Glytec, who will be leading today’s presentation.  Dr. Messler, you now have the floor.

JORDAN MESSLER:  Great.  Thanks so much, Laura.  Thanks, everybody, for joining this afternoon.  Appreciate you taking the time as we talk about glycemic management in the hospital and lessons from COVID-19.

A brief bio about myself if we haven’t met before – certainly, enjoy meeting you here virtually today.  I’m executive director of clinical practice at Glytec.  I also practice clinically as a hospitalist.  I was former medical director of our hospitalist program at Morgan Plant up until 2014.  I continue to work clinically there and at BayCare Hospitals in the area here in Clearwater.  I’m also adjunct faculty at USF Morsani College of Medicine in medical humanities.  And I’ve spent a lot of time at the Society of Hospital Medicine – former chair of their quality and patient safety committee and currently serve as their physician editor for The Hospital Leader blog.

For today’s session, we’re going to go through a few things, talking in particular about the prevalence and impact of diabetes and stress hyperglycemia in the hospital and then relating that impact for patients with COVID-19.  We’ll review the guidelines and the management of hyperglycemia in the hospital and touch on briefly the management of steroids, which has been one of our integral therapies for patients with COVID-19.  And then we’ll end talking about some of the newer technology that’s out there to manage our patients with diabetes glycemia in the hospital and that assist in the management of insulin. 

COVID-19 really has exposed what we know, what many of you in the audience know, that there’s an urgent need to improve how we manage diabetes and glycemia in the hospital.  We know this was an increasing need prior to the pandemic.  This GIF will continue to flow through the colors – oh, it doesn’t look like it’s flowing through the colors.  But if you haven’t seen this CDC GIF, it usually goes from blue to red pretty quickly, talking about the increasing prevalence of obesity and diabetes in the hospital.  This GIF generally becomes red pretty rapidly and clearly by 2010.  In that last bullet at the bottom, 30.1 million people with diabetes, and its prevalence has quadrupled from 1980 to 2014.  That’s going to continue to rise.

So to talk about diabetes and hyperglycemia in the hospital, I want to throw our first poll of the day.  We’ll have a couple of these as we go through the presentation.  What percentage of inpatients with diabetes and hyperglycemia may require insulin?  So the poll is live, and we’ve got 20%, 40%, 60%, or 80%.  So click in your answers.  We’ll just give it a few more seconds.  Everyone looks like they’re replying rapidly to the poll.  I think we’ve got over half, so we’ll end the polling.  Thanks for clicking in.

It looks like we can see the results.  We’ve got 20% at 5%, 40%, 14%, and many of you picked 60% or 80%.  Let’s go through what the answer is on these next slides.  So what is the status quo of inpatient glycemic management?  What is happening currently?  We know that one in three Americans have glycemic control issues – diabetes or prediabetes.  We know insulin is one of our high-alert medications – one of our top three high-alert medications, in addition to opioids and anticoagulants – and insulin involved in 16.3% of medication error reports.

And then the prevalence of diabetes hyperglycemia in the inpatient setting that’s requiring insulin – up to 40%.  So 40% was the correct answer on that poll.  So 30%, 40% of inpatients require insulin therapy during their hospital stay.  Now, many of you may be seeing those numbers go up, as per that CDC GIF that I showed earlier.  We certainly work with hospitals that’s seeing that number approach 50%, and maybe in your setting, you are seeing those numbers continue to rise.

In particular with COVID-19 – we’ll talk a bit about this – steroids is one of the treatments for COVID-19, and we know that up to 80% of our patients in the hospital meet indications for steroids, certainly contributing to hyperglycemia in the hospital setting.

So that number of 40% comes from this work from Dr. Umpierrez in 2002, showing that in the hospital setting, about 26% with diabetes, 12% with new hyperglycemia.  He defined that with these random blood sugars greater than 200 times two or an elevated fasting blood sugar.  So really approaching that 40% with diabetes or hyperglycemia.

Really, the other big finding with that was this group of stress hyperglycemia we talk about – this basically new hyperglycemia that subsequently after they leave the hospital, where those blood sugars do return to normal or may have normal A1Cs.  This stress hyperglycemia group – that itself is serving as an independent marker of in-hospital mortality.  That is a group that for a variety of reasons are at higher risk for mortality.  And this is a group that we need to continue to pay attention, and we’ll talk about how we’ve looked at a similar group with COVID-19.

So the impact of COVID-19 on diabetes – I think we’ve been all really seeing this impact in particular on this group of patients.  I like this visual talking through some of this basic physiology.  There’s much more in-depth physiology to try to understand the pathophysiology of how SARS-CoV-2 may be impacting diabetes.  In particular, we’re seeing an impact on beta cell damage and the cytokine storm that we see. 

So this combination contributes to what we recognize as worsening metabolic control.  We’ve seen this translated as high blood sugars.  One of the reactive markers is blood sugar – so in addition to other markers that are rising as patients with COVID-19 pneumonia in the hospital, and that translates to high blood sugars on admission.  On the right side here, potentially new-onset diabetes.  A recent report from the ADA suggested about 14% of patients are developing new diabetes after COVID-19. 

And then this worsening metabolic control in patients with diabetes, and we know all these risk factors that are contributing across the bottom here – obesity, inflammation, coagulation, impact on the immune system, these hyperglycemic crises, older age, cardiovascular disease, and renal disease.  Patients with diabetes have these risk factors to begin with.  Throw on top of it this risk from SARS-CoV-2 – beta cell damage, cytokine storm – it’s just a recipe for poor outcomes.

Going back to the prevalence of diabetes at baseline, we said one in three Americans have prediabetes or diabetes.  About 10% of Americans have diabetes.  But in the hospital setting, we saw that number rise to 20-28%.  And then critical care setting, the number rises even higher – in some studies, up to 60% of patients in the critical care setting with diabetes.

So our COVID patients are facing these unique glycemic management challenges.  We’re seeing these patients with diabetes at risk for worse outcomes.  Again, the point that up to 80% of these patients, based on the recovery trial from over the summer, are on steroids, and the steroids contributing to hyperglycemia. 

And then the environment around the pandemic has created a lot of new challenges.  These challenges have ebbed and flowed throughout the past year-plus, but in particular early on, PPE preservation increasing the concerns for entries into room, protecting our frontline health care workers and leading to less frequent blood sugar checks.  These concerns haven’t gone away.  We’re seeing, obviously, continued surges and recurrences and need for continuing to find ways to help preserve PPE and other strategies.

In particular, a variety of strategies and lessons were being passed around over the summer and made a major way into how you’re managing diabetes in the hospital.  I’ll go through a few of these.  There may be a variety of ones that you have considered, have implemented, maybe even backing off on many of these that you had tried and implemented. 

But in particular, trying to find strategies to reduce those hourly checks for patients with IV insulin with frequent entries into the room, frequent potential for exposure for frontline workers – strategies such as managing mild DKA with subQ insulin.  Certainly, a really efficient, effective strategy is trying to find ways for nurses to bundle care to minimize entries into the room.  Minimizing the use for IV insulin.  Perhaps you or your colleagues have worked on strategies where maybe you set different thresholds for starting IV insulin, earlier transitions from IV to subQ, maybe add a new risk stratification for patients already exposed.  In general, we know that stress hyperglycemia is a risk factor, and we’ll discuss the data around COVID-19 that those particular patients are at high risk.  And you may have wound up changing your protocols for managing.  Some institutions have tried to implement continuous glucose monitors, and we’ll highlight a case study done at Emory where they did a hybrid model with CGM and point-of-care testing.

In general, as you’ve been implementing all these strategies, one key quote that caught my attention over the summer from some of our diabetes experts nationally when they put together this pragmatic approach to inpatient diabetes during the pandemic – and just to keep to mind with anything that we’re doing that’s new.  This was clearly a new disease and something that we really had to face without much knowledge at the beginning.  “It is generally recommended that hospitals not make major changes to their current approach to managing hospitalized COVID-19 patients with hyperglycemia due to concerns that this alone can increase risk for unintended consequences, requiring more time at the bedside.”  So many of the strategies I talked on the prior slide you may have tried to implement, but hopefully all being mindful that this may increase the risk for hypoglycemia – doing new things without evidence – and certainly hyperglycemia, if we’re delaying starting IV insulin on patients where we normally were.

Now, obviously, sometimes you had to do this for practicality – PPE shortages.  But I would certainly be mindful if you’re not facing those surges, and you have enough PPE, that really re-looking if you had made some major changes to your protocols for glycemic management.

Let’s look at the evidence.  We’ve been fortunate enough at Glytec to partner with some national leaders and really try to ask these questions – what was the impact of glycemia on outcomes for our COVID-19 patients?  One of the studies that helped really define this risk was out of China early on that patients with diabetes had worse outcomes with COVID-19, and in particular, those poorly controlled with worse outcomes.  That’s visualized on this graphic that they used in the paper on the right, showing that well-controlled in the blue line, those 70-180 patients, had a survival of 98.9%, or a death rate of 1.1%.  And those poorly controlled, greater than 180 during the hospital stay, had a mortality approaching 11%.  In particular, they showed a hazard ratio of 2.9 for death for patients with diabetes and a higher risk for those severe outcomes that we know are evident with COVID-19 – ARDS, acute renal failure, septic shock, and DIC.

So we asked similar questions as well.  We published this in April in the Journal of Diabetes Science and Technology, looking at the comparison of diabetes and/or stress hyperglycemia versus patients with COVID-19 that had normal blood sugar in the hospital, and saw this 28% mortality, versus normal glycemia at 6.2%. 

This brings us to our second poll.  Again, that group with stress hyperglycemia that I mentioned earlier – what’s the mortality risk for stress hyperglycemia patients with COVID-19 compared to patients with normal glucose in the hospital?  So we will pull up our poll.  I see some folks are answering.  So three times higher, seven times higher, three times lower, or seven times lower?  It looks we got over half answering.  We’ll give you another couple of seconds.  

All right.  So thanks for answering the poll, and we’ll show those results.  It looks like pretty much the vast majority said higher, so let’s go through the paper and show how much higher.  We split that group up of stress hyperglycemia and diabetes to really examine the impact, showing that that stress hyperglycemia had really a seven times higher risk for mortality compared to normal glycemia.  That was that greater than 180 times two group that had no evidence for diabetes with normal A1Cs.

So that seven times higher mortality – certainly, other comorbidities translated, too, as well.  This group with uncontrolled hyperglycemia or diabetes had a longer length of stay in the hospital as well.

We followed up with this study.  Were these patients at this high blood sugar just sort of a marker of worse disease?  Is there something that we can do during the hospital stay to control their blood sugars and show the outcomes of getting patients controlled while they’re in the hospital?

We used a surrogate for this opportunity window.  We know that patients in the ICU setting that are placed on IV insulin for hyperglycemia can be controlled in a matter of hours.  We looked at one day, 24 hours.  And patients in the non-ICU setting that were managed with subQ, from evidence from RABBIT 2 and other studies, we can generally get most patients controlled within two to three days.

So we looked at this two- to three-day window particularly – the non-ICU group, I’ll highlight here – as the target blood sugar opportunity window.  The patient comes in with hyperglycemia.  Start them on standard of care – basal-bolus.  Most patients within two to three days should begin to get in control.  This particular group I’ll highlight on the graph – you could see here also had that seven times higher mortality rate.  Unfortunately, this group, we saw again this higher mortality rate if they remained severely hyperglycemic at that window, two to three days. 

This is evident in the graphic that we have on the left here, that red bar – clear separation early on, persistent hyperglycemia, not getting under control after that window of two to three days – this is the greater than 250 group, and they had seven times higher mortality than patients that were able to achieve control.  Unfortunately, it seemed that over half of our patients remained over 180 at day two to three.  So we know we can get patients in control, and the majority of these patients were not in control at day two to three.

This isn’t surprising.  The results aren’t surprising.  We know we have challenges getting patients in control.  But the results as well aren’t surprising.  We’ve seen this before.  It’s not just COVID-19.  Sepsis, coronary disease, pneumonia, stroke, critically ill with continued hyperglycemia or stress hyperglycemia have worse outcomes.

Again, on the right here, highlighting that we can get these patients in control.  This has been shown in studies as well.  In the ICU setting, we can get patients controlled in as little as six hours on IV insulin.  So we used a window of 24 hours, and in the non-ICU setting, within two to three days using a subQ basal-bolus insulin regimen.

Again, hyperglycemia on admission as a marker for worse outcomes – that was part of this as well.  In particular, the ICU patients with admission hyperglycemia was a marker for worse outcomes.  And good glycemic management during the hospital stay leads to better outcomes.  Dr. Umpierrez was a co-author with us on this paper, and following publication said, “this research suggests that blood sugar should be high on the order set for COVID-19 patients irrespective of a preexisting diabetes diagnosis.  We can control blood sugars in the hospital, but for a variety of reasons, this study shows that it’s not happening or hasn’t been a priority for COVID-19 patients.  Our findings strongly suggest that early intervention to bring blood glucose into target range will reduce mortality rates in COVID-19 patients.” We can’t delay care.  If you have hyperglycemia on admission, we need to act, get these patients under control – in the ICU setting, IV insulin, in a non-ICU setting, basal-bolus regimens.

As a summary of these findings around diabetes and COVID-19 – our first paper that we mentioned, the Dr. Bode study, stress hyperglycemia leading to worse outcomes.  The study from China, similarly – stress hyperglycemia, and really, diabetes poorly controlled had worse outcomes.  The work with Dr. Klonoff and others that we did showing the opportunity window that we just highlighted – admission blood sugar in the ICU setting leading to a predictor of worse outcomes, and patients with persistent hyperglycemia – day two to three in the non-ICU setting – with seven times higher mortality.

I didn’t go into detail on this last study, but this is one of those few studies during the pandemic which confirmed what we’ve seen in other studies, that getting patients prospectively on insulin – this is a group with moderate COVID-19 that they placed on insulin.  It was a small study.  But it did show the protective effect of getting patients in control, the protective effect of being on insulin, had better outcomes.

Thinking through all these results and thinking through how you’re managing COVID-19 patients today, how you’re managing hyperglycemia in general, and then combining the two, I’m sure many of you have checklists for how you’re managing COVID-19 – if it’s not a physical paper checklist or in the EMR, a mental checklist that you’re trying to do for your COVID-19 patients.  What’s on your checklist?  Here, clearly highlighting glycemic management – is that on your checklist?  Certainly, oxygen for patients that are hypoxemic.  Proning has been a strategy that certainly is relatively simple, even if it doesn’t have a huge amount of evidence, that we’ve been doing for our patients.  Delayed ventilation.  Remdesivir is part of many protocols with hypoxemia.  DVT prevention – preventing blood clots in the hospital setting.  And then the management for steroids for those patients with hypoxemia.  But is glycemic management also on that checklist?  Is it a primary thought when a patient comes in with hyperglycemia, or is it a secondary thought?

So I thought I’d spend the middle here just reminding us and talking through the guidelines and reminding the standards of care.  This is 2021 guidelines with no major changes that have happened for basic management of hyperglycemia in the hospital setting.  We know in the critical care setting, as I mentioned, that continuous IV insulin is the most effective therapy for achieving targets.  And as they state in here, insulin therapy should be started for persistent hyperglycemia.  I’ve certainly worked with sites where IV insulin is started right away for hyperglycemic crisis, DKA, HHS.  But for patients that are in the ICU setting that have persistent hyperglycemia greater than 180, how are you managing them?  Are you just getting a dose of basal?  Are you doing sliding-scale insulin?  Or are you following guidelines suggesting that these patients should also be managed with IV insulin when they have persistent hyperglycemia?

In the non-ICU setting, we know that basal-bolus is the preferred method.  So long-acting insulin plus short-acting insulin with meals, bolus or prandial insulin, nutritional insulin, plus correctional insulin is preferred for those eating.  For patients that are NPO or poor oral intake, basal plus correction.  And then we know to avoid sliding-scale insulin only or a reactive approach to hyperglycemia in the hospital.  And the goal for most patients is 140-180.

So a basic outline – as we’ve been talking here, hospitalized patients with hyperglycemia in the critically ill setting – IV insulin with the goal, generally, of 140-180.  In some situations, you can tighten that goal.  For surgical patients, for patients that you can safely manage with minimal hypoglycemia on a protocol like Glucommander, which we’ll talk about a bit, to manage IV insulin, you may be able to lower that goal.  But in general, 140-180.

In the non-critically-ill setting, basal-bolus therapy for patients that are eating is the standard, with the goal also of 140-180.  And based on some other clinical situations, you might adjust that goal, but that’s generally the targeting goal.

So I wanted to touch briefly here on DKA management, because this is one of the strategies that were discussed early on to manage DKA outside of IV insulin.  I’m not going to do a deep dive of the literature on there, but there is some evidence for managing mild DKA with subQ insulin.  Dr. Umpierrez has published on this in 2004.  There have been some subsequent studies – and basically non-inferior in these studies compared to IV insulin.  I would highlight that this was for mild DKA management.  Many of you might have tried to minimize the use of IV insulin by implementing a strategy like this using subQ insulin every couple hours or maybe using a basal dose followed by short-acting every four hours.  There’s a variety of protocols that are similar to these to manage DKA.

But again, this would be mild DKA.  I want to highlight some work that we did recently – published this with Dr. Pasquel and others, Dr. Aloi – looking at DKA patients with or without COVID-19 in the hospital.  We looked at 4,819 patients without COVID-19, 210 patients with COVID-19, and looking at their results. 

We know that the mortality rate in general for patients – and most of these have been pediatric studies.  This is an adult study population.  We know the mortality is generally less than 3%.  That’s been improving over time, and mortality is quite low for patients with DKA.  So this bucket here, this less than 45 without COVID-19, is the only bucket that was really at the rate that we’d expect.  But with increasing age without COVID, with increasing age with COVID, we had a significant difference in mortality.  You can see here in this group greater than 65 – mortality over 40% in this group that met the definition by laboratory for DKA.

So in my mind, look, we see that these patients have a high mortality with COVID-19 in general, with DKA a high mortality.  We certainly should be managing them with the standard of care, which would be IV insulin.  So these patients required longer courses of IV insulin to get to target compared to the patients without COVID-19.  We just recognize that they’re sicker.  They have increased mortality, morbidity, and they need to be managed with IV insulin.

A brief review of the non-ICU setting.  The standards of care there – we know in particular things we do for no reason – this was published a few years ago in the Journal of Hospital Medicine.  Sliding-scale insulin as monotherapy for glycemic control in hospitalized patients is something that we do for no reason.  This is a very reactive approach.  There are some studies for patients with mild hyperglycemia, less than 180 with diabetes, that may be OK to manage with sliding-scale insulin alone.  But for the vast majority of our patients with hyperglycemia, sliding-scale insulin alone – if that’s happening, that is outdated therapy, and it’s something that we do for no reason.

Looking through basal-bolus management in the hospital – this graphic to illustrate how we manage basal-bolus in the therapy.  TDD is the total daily dose of insulin.  We’ve generally split it up 50% basal long-acting insulin, 50% bolus prandial insulin, and then we divide up that mealtime insulin evenly between each meal.

The way I use to decide how to start the regimen – really, based on a patient’s home regimen.  Are they on insulin at home?  Are they not at insulin at home?  Help decide the initial starting dose, which is really the most important point – getting them on the right dose on initiation.  Certainly, don’t set the dose and then forget it.  We have a huge issue in managing basal-bolus therapy in the hospital, and we get clinical inertia.  We picked that great dose.  You did the math.  And then you forget to adjust the regimen daily based on changes in the patient’s clinical situation.

So I thought I’d go through a couple quick clinical examples on how we manage and how we pick that initial dose for patients on basal-bolus.  If they’re on a home regimen, simply clinically we tend to look at their home regimen dose, add it all up, calculate their TDD, their total daily dose at home.  We tend to lower that by 20%, 25%.  We know patients eat a lot less in the hospital.  And then if we’re on Glucommander, we’ll select that target range, which we have personalizations to choose the target range that you want.

An example here – a patient that is on 70/30 twice a day, 50 units in the morning, 30 units in the evening.  Simple math – 80 units is their total daily dose.  Obviously, we’re confirming with the patient that that is what they’re taking, and then tend to reduce that by about 20%.  So for this example, you’d get 64 units and then split that up 50/50 – 32 units of basal, 32 units of mealtime insulin, and divide that mealtime insulin evenly for each meal.

If they’re not on home insulin, we tend to use weight-based dosing.  So a variety of ways that you may do this at your institution, but generally from RABBIT 2 trial, we know 0.4-0.5 starting dose units per kg per day.  For renal issues or hypoglycemia risk factors, we’ll lower that to 0.3.  And very rarely, we might find a starting dose of 0.7 units per kilogram per day.  Then, we’ll select a target range as well if they’re on Glucommander.

So an example here – someone that weighs 70 kilograms, normal kidney function, they’re not on home insulin, they’re coming in with hyperglycemia in the hospital, you could do a standard start of 0.5 units per kilogram per day.  So 70 times 0.5, that gets you to 35 units total daily dose.  You’ll split that up evenly – 18 units basal, 18 units bolus, and divide that bolus dosing evenly.

So a quick review as well to understand where those recommendations come from.  If you haven’t reviewed the literature recently, the work from Dr. Umpierrez over the years really helped setting the guidelines in how we manage with insulin in the hospital for hyperglycemia.  The RABBIT 2 trial – really, our first prospective trial looking at basal-bolus compared to sliding-scale insulin, and basal-bolus more effective.

I did want to illustrate that difference here, in particular to highlight the basics of our study that we did for that opportunity window showing that within two to three days, we can get patients on average in control between 140 and 180 on basal-bolus, but not on sliding-scale insulin.  Many of those patients on sliding-scale insulin only did fail therapy and were eventually transitioned to basal-bolus.

And then the outcome study subsequently, RABBIT 2 surgery, is really showing us the impact.  On even a short hospital stay, just several days in the hospital – in this study on average, they were in for about six days – and this composite outcome was significantly different in that group in green on sliding-scale insulin alone compared to the group here in red, purple, whatever you’re seeing, the basal-bolus group here.  So a significant difference in the composite outcome for patients that were managed on basal-bolus versus sliding-scale insulin alone.

I want to talk briefly on some medications – sitagliptin, steroids, and COVID-19 management.  Really, in general, for recommendations and the way they are in the guidelines that oral medications that patients are on for diabetes are generally stopped.  Many of them have contraindications while patients are in the hospital – sulfonylureas, risk for hypoglycemia.  Metformin, we know contraindicated with certain conditions such as heart failure.  But there have been some studies over the studies over the last few years with DPP-4 inhibitors – sitagliptin, I’ll highlight one of them.  There have been several other studies since this – since 2017. 

This one was Sita-Hospital and looked at hospitalized patients on basal-bolus insulin compared to a regimen with basal and sitagliptin – and non-inferior.  This wasn’t designed to go through a deep dive of all the other literature.  I certainly suggest that you review that.  They’re not in the guidelines currently, but they may be coming.  There is evidence of the safety of using the DPP-4 inhibitors.  But generally, those are patients that are fairly well controlled, so less than 200 in the hospital, might find some benefit from using DPP-4 inhibitors.  Subsequent trials, particularly in surgical patients, those patients go over 200, seem to have more benefit with basal-bolus and not using an oral agent.  But more to come here.

I did want to highlight this as well, because there were a couple of studies that got attention in Diabetes Care at the end of the year or at the beginning of this year using sitagliptin in COVID-19 patients.  There is some pathophysiology that makes sense on how DPP-4 is used in the cell, and SARS-CoV-2 may potentially use DPP-4 as an entry into the cell.  So there was some physiology that made sense. 

This was a study out of Italy.  There were a couple at the time – I’ll highlight one of them – looking at sitagliptin treatment at the time of hospitalization associated with reduced mortality in patients with diabetes and COVID-19.  The key things to highlight in the title, just to go back real fast – a case-control, retrospective, observational study.  We’ve certainly got to be mindful of the type of study.  It’s not our standard of care, prospective, randomized controlled trial.  It did show an impact on mortality with the sitagliptin versus standard of care.  There was some suggestion that there’s some physiology that would make sense. 

But I would be very mindful of the potential bias on here.  This was one study that was not prospective.  There was no placebo.  And in this area in Italy, because of some of the physiology, some local practice patterns, there was a lot of increased prescribing of sitagliptin outpatient, so there may be some bias to that.  There may have been a group of patients that had different access to health care, and that may be why they did better as well.  So it raised interesting questions and certainly warrants further study before we change practice.

I touched briefly on steroids.  We know steroids – again, standard of care with patients with hypoxemia and COVID-19 in the hospital.  From the recovery trial, it was about 75%, 76% of those patients met that criteria and were placed on dexamethasone – 6 milligrams a day for a 10-day course.  So steroids since the summer has really been the standard of care for patients with hypoxemia.

And we know that a vast majority, over 50% of patients without diabetes that are placed on these steroids – placed on high-dose steroids – develop hyperglycemia, and 80-100% of patients with diabetes will have worsening hyperglycemia when placed on steroids.  So how are you managing these patients?  There isn’t a huge lot of literature.  There are some small studies out there – a variety of different steroids, different regimens that are tried.  Certainly recommend reviewing it.  This is an area that would benefit from more prospective research.

But the basic principles to apply – and many of you may have different protocols that you’ve used – for dexamethasone, which is a long-acting steroid, in general, you’re increasing a basal-bolus regimen that they’re on.  There are some guidelines from the UK that discussed using NPH BID with a higher dose in the morning and a lower dose in the evening.  And recognizing that these patients – that that 0.5 units per kg per day is a starting dose, that they may need up to really 1 unit per kilogram per day.  So be very mindful of how patients respond and may really need to increase their insulin needs.

If you’re using prednisone – so prednisone management – this was updated in the 2021 guidelines with more specificity from the ADA on managing prednisone.  In general, NPH matches the physiology for prednisone, so prednisone dosed in the morning would benefit from NPH once a day in the morning, and there are some tables to get some equivalent dosing.  So AM NPH for AM prednisone and BID NPH potentially for BID prednisone.

Other options to consider – there have been some good studies suggesting that the steroid impact really is postprandial, so the 50/50 split that I talked about to manage basal-bolus may become a 40/60 or 30/70-type split when you’re managing patients on steroids.  If you don’t start it that way, you might find that’s what they ultimately need after being on steroids for several days, and certainly keeping in mind when you stop the steroid that the added insulin will need to be reduced.  Or if they – just stress hyperglycemia or hyperglycemia without diabetes, that the insulin will be removed after they’re off the steroids.

All right.  So we’re getting to the last piece here – really, the last 10 minutes or so here – and wanted to talk about technology in the hospital, a few things that are here, that are coming, and thinking through about diabetes technology in the hospital setting. 

So not just technology, but a lot of things have changed rapidly in the hospital setting over the past year.  Just to think of a few of them, we obviously went through some research that we’ve done.  The research around COVID-19 has been at a huge rate – 300,000-plus articles related to COVID-19.  No way to stay up on top of the literature, and literature with all sorts of different biases within there. 

We certainly are all facing volume fluctuations – very difficult to respond, very challenging throughout the year, lows early on, surges in between.  Front lines have been taking on a lot of different roles.  I’ve had colleagues in different disciplines – surgical disciplines that are now placed on the front lines.  We’ve seen various other frontline health care workers that are in departments that they weren’t used to. 

Medical education certainly has transformed.  Remote learning – many of our learners unfortunately had their clinical opportunities reduced for good reason.  And then conferences, education, how we teach has all had to adopt to the virtual world.  Some of the technology we’ve seen may relate to how you’re managing diabetes, but really just in general, the acceleration of telehealth – not just outpatient, but inpatient – remote monitoring of patient vitals.

And then this really goes into this next piece here.  We’re rapidly adopting new technology.  So how are we doing that?  I want to talk through a brief framework to think through how we’re adopting new strategies.  This certainly came to light in the past year.  This was from the Harvard Business Review.  This is a good strategy to think through any time you’re doing something new.  Clearly, this was a crisis that forced us to change. 

And, number one, seeing the system differently – it has certainly forced us to see things differently.  It really forced us to look at how we’re managing – make sure that we’re getting different perspectives, maybe even an outside voice in how we’re going to implement something new.

Number two there – making sure that we have a bias towards action.  This is always important to keep in mind when we’re trying to do something new – the ability to learn from when we make mistakes, the ability to fail faster, the ability to really just test out new things.

In the middle there – unfreeze the organization.  We know that we frequently really exist in silos, don’t always do the teamwork that we want.  But this is an opportunity to make sure we unfreeze, consider change management strategies, talk through different teams on how we can work together and really implement something new. 

Clearly, the pandemic forced us to unite around that singular purpose.  Always thinking through what that purpose is for the team as we implement something new.

And then problem-solve together and innovate.  As we think of innovations and technology, this brings us to our last polling question.  What new diabetes-related technology do you see in your hospital in the next one to two years?  So you can see the polling question up there – glucose telemetry, insulin management software, enhanced analytics, continuous glucose monitoring, and you can select more than one.  So we’ll give that a few seconds for everybody to click away.  Thanks for answering the poll.  It looks like we’re getting over half, so I’ll give it another couple of seconds, and then we’ll end this poll.

All right, so polling is closed, and we should be able to see the results.  So glucose telemetry, which we’ll talk to briefly, about 10%.  Insulin management software, almost half of you.  Enhanced analytics, a third.  And many optimistic that in the next couple years, you’ll see continuous glucose monitors entering the hospital setting.

Let’s talk through a few of those.  Insulin management software – so our company, Glytec, has Glucommander – I’ll talk about that briefly – dashboards and analytics, and continuous glucose monitoring.

Here at Glytec, we have Glucommander.  For those not familiar with it, it is insulin management software, an FDA-cleared solution that we integrate within the EMR to get personalized insulin dosing.  So we’ll start on this top left with Glucommander.

But it’s not just Glucommander.  I want to highlight some other features – our suite of solutions that helps support the insulin dosing software that we have, Glucommander.  This operates in the cloud, so we can do remote implementations, remote upgrades. 

GlucoMetrics I’ll talk to briefly on the next slide.  Analytics and reporting are certainly vital if you’re doing anything new and trying to measure change.  You’ve got to be able to see the data to see how you’re doing. 

We have a solution called GlucoSurveillance, so part of our solution monitoring patients that are not on Glucommander that are having that greater than 180 – multiple readings over 180 that would benefit from being on insulin therapy.  

Our SmartClick is our solution to have that easy integration within the EMR, so for the end user, it’s a seamless integration within the EMR.  It’s not a separate website or a separate module.  It appears within your EMR. 

And then GlucoView – certainly important for patient monitoring, monitoring a variety of alerts.

And then in the center here, all this – our team works closely with your team.  Hopefully, your institution has a glycemic management team.  It may be just a couple of people.  It may be a full multidisciplinary team.  And our team works closely with your team to not just implement, but optimize and continue to improve glycemic management at your institution.

I think a key piece is GlucoMetrics.  I’d like to highlight the data piece.  We have a suite of solutions called GlucoMetrics, and I would take this moment to think at your own institution, what kind of data that you do get around glycemic control.  Unfortunately, there’s usually a lack of data – very little insight.  One of the reasons – Dr. Umpierrez’s quote earlier – a variety of reasons we don’t control blood sugar very well, and one of them is that we don’t have much feedback.  We don’t get much data, whether it’s real-time information or subsequent feedback on reports.  If you do get information, it’s generally perhaps just one report on hypoglycemia rates.  But we think it’s important to get a variety of measures out to you so you could see how you’re doing on hypoglycemia or hyperglycemia and control and how you’re managing glycemia and insulin in the hospital setting.

So for the last piece here, I’ll talk briefly about continuous glucose monitors, and I want to thank in advance Dr. Pasquel.  They recently published at his institution a hybrid model that I’ll go through here.  I’ve used many of his slides to talk about what they did at Emory and at Grady to use a hybrid model of continuous glucose monitoring.

I want to highlight this first point, that CGMs are not approved for inpatient use currently, but the FDA does not object during the pandemic.  So there still is a process for CGM to get through clinical studies and get approved for inpatient use.  Maybe you’re using them at your institution or considering CGMs, but that is the way it was written back in April is really a non-objection sort of allowing CGMs during the pandemic, and it’s unclear exactly when that would end.

Manufacturers recommend against using the sensor data for making treatment decisions.  Point-of-care blood glucose is recommended for insulin dosing for now.  Certainly, used as a supplement to help monitor trends.  And really, the big thing, and many of you may have learned this, is that infrastructure does require a high lift – really having that staffing, team-based approach, educational support, clear expertise, and protocols to implement continuous glucose monitors in the inpatient setting.

For guides and for reference, I’ll refer to this article – Dr. Galindo and others have been doing a lot of work on this nationally – implementation of CGM in the hospital and considerations during the pandemic. 

I do want to highlight some studies that have been using CGM in the non-ICU setting.  This glucose telemetry model is the work of Dr. Spanakis and others looking at using continuous glucose monitoring really to track trends, in particular looking at patients that are starting to get below range, less than 100 – opportunity to intervene before they develop hypoglycemia.  So patients are getting their sensor – one of these studies had the Dexcom sensor, a bedside unit, and then transmitting that information to a centralized area – a nursing station where they could see glucose values over time, have trends and alarms, and then they would have a team that would intervene in certain situations.

For the study that was recently published by Dr. Pasquel and others, I’ll go through their model of using a hybrid model – point-of-care testing and continuous glucose monitoring.  On the bottom left here, using both CGMs and every-six-hour glucose point-of-care testing in the ICU IV insulin setting.  So getting that CGM device on a patient, having a device within about six meters, 20 feet, getting that information out into the cloud and would translate to a nursing station.  There was a follower team, the endocrine team, that could keep track of multiple patients, and in addition, could also have population health management afterwards, and all this information flowing into the EMR, CGM, and point of care to help make decisions.

So their model – and again, courtesy of Dr. Pasquel for some of these upcoming slides here to talk about remote CGM with point-of-care every six hours with Glucommander that they have at their institution and using the EMR for documentation or validation.  They used the Dexcom G6 CGM for their protocol.

Let’s go through this briefly.  The article goes in depth on how they use this as well.  So the patient would have a sensor.  They’d have a smartphone receiving a Bluetooth signal outside of the room.  So the blood sugar they could see on the phone in a lockbox.  They also went through a process, and many of you might have tried this, where they had the pumps outside the room as well, so they could see the blood sugar and then adjust the pump without having to go into the room.  This does have some issues, and many of you may have tried this and reverted back to having the pumps back in the room.  It required a lot of extra tubing, and you had to be really cautious.  But one step they did to try to really minimize entries into the room.  And then the glucose telemetry at a nursing station, so they could see it as well at a centralized station.

On the left here, we see the CGMs monitoring and then a similar graph that was happening within Glucommander as they were entering the blood sugars hourly or when needed in Glucommander and really how they correlate closely.  This one line here is when they lost some CGM sensor.  This is when the patient had an acute clinical event – a cardiac arrest – lost some of the sensoring and then picked right back up.  You can see it matched up well here.

They did have a validation process.  So the first couple of hours, they had CGM reading and validated with point-of-care testing, and they had to have those readings within 20%.  So the CGM readings needed to be within 20% of the point-of-care.  To try to minimize calculations by nursing, they had a process that they did in the EMR to validate that so the nurses didn’t have to do calculations and make sure that was in the validation range.  They had some other protocols – if the CGM was less than 100, then they would have to validate that with point-of-care testing as well.  And other acute clinical changes would have to validate with a point-of-care.

And then after validation, after a couple hours, continue using the CGM monitoring.  Every six hours, they would have a point-of-care to make sure that it still met validation criteria.  Enter the blood sugar into Glucommander to get the updated infusion rate that you would get from Glucommander.  And again, for certain situations, they would also confirm with point-of-care testing.

So to highlight what this would look like in one particular patient out of the study – I’ll just orient you here quickly to one example.  These hashmarks are showing the start of IV insulin – the gray is insulin – and then ending when the IV insulin infusion ended.  The blue is the CGMs and the green is the point-of-care.  So you can see the lines tracking very closely – the blue CGM readings and the green point-of-care testing – and they highlight for these patients – again, these are critically ill patients in the ICU, and unfortunately, many of them did have acute events.  So they highlighted when those were happening and perhaps loss of signal on the CGM during these cardiac arrests, and then they relied on point-of-care testing.  But then it did pick back up.

I won’t go through all the cases here, just highlighting what’s in the paper.  So if you’re interested further, you can look at the nine patients that they looked at here, and really their conclusions showing that this is feasible, that using this hybrid model – continuous glucose monitoring with point-of-care testing every six hours – they were able to safely manage these patients.

So bottom line for CGM use – again, the FDA is not objecting to the use of continuous glucose monitoring during the pandemic.  The Dexcom G6 and the Abbott FreeStyle Libre are the ones that are being used in the hospital setting.  They do not require calibration.  CGM use with a computerized algorithm – in this case, it was Glucommander for insulin management and EHR documentation to ensure validation – is feasible and effective.  They did a hybrid model, as did others at Ohio State, too – also some publications from them – is recommended and is feasible.  And they were able to reduce what would be hourly checks – in general, about 20-24 per day on IV insulin, may even be more than that – down to about eight per day.

And then the bottom line for the rest of what we went through – we could see worse outcomes in patients with diabetes and COVID-19, unfortunately, for a variety of factors – in particular, stress hyperglycemia, admission hyperglycemia related to higher mortality.  Insulin remains the mainstay of management – IV insulin in the critical care setting, basal-bolus in the non-critical care setting.  And the use of oral agents, DPP-4 inhibitors, with some potential. 

And then rapidly doing change – one, don’t radically change practice.  Be mindful of unintended consequences.  Certainly, ask questions.  Use a variety of perspectives.  And we’re seeing here there’s a really great opportunity when done well for technology to assist in care.

So I really appreciate everybody coming out to the webinar today or for those that are watching this remotely after the fact.  Thanks so much for your time.  That gives us a few minutes to be able to answer some questions.  So I’ll pass it back to Laura.

FLYNN:  Great.  Thank you so much, Dr. Messler.  Yes, we do have some time for Q&A.  So as a reminder, you can enter any questions you have into the Q&A box at the bottom of your screen.  Anything we don’t get to today, we’ll be sure to have somebody follow up with you directly after the webinar.  And we’ll continue to leave Jordan’s information up on the screen if you do think of anything after the webinar or if you’d like to schedule some time to speak with a member of our team.

OK, so first question we have is from John (sp?).  He said the CGM study is very exciting.  Do you anticipate that the FDA could approve CGMs post-COVID?

MESSLER:  Yeah, so thanks for that question.  It was great to talk about continuous glucose monitoring and the work that’s being done nationally.  Again, the FDA is allowing for that during the pandemic.  I’m not sure when that allowance will stop or the definition for when the pandemic period is over.  Post- that period, I think it relies on some of the clinical studies to be done.  Is that timeline going to be possibly in the next couple years?  I really don’t know for sure.  It depends on the clinical studies.

FLYNN:  Great, thank you.  Next question we have is from Chris (sp?).  Chris is asking if the studies that were referenced and the presentation – if that will be available to attendees.

MESSLER:  Yeah, great question.  At Glytec, we’ve been really working closely with a lot of institutions.  We have a lot of research on our website,  We have 90-plus studies that are all available there, including the ones that I highlighted that we had done on COVID-19.  In addition, all those particular references and studies will be available afterwards and the slide deck after this webinar.

FLYNN:  Great.  The next question we have is from Debbie (sp?).  For steroids, are you saying adding NPH to the basal-bolus or switching to NPH?

MESSLER:  Yeah, great question.  Sorry I wasn’t clear talking about steroid management.  Went through it fairly briefly.  But yeah, for a patient with diabetes that you’re managing with basal-bolus, and you’re getting them started on dexamethasone, which is a long-acting steroid, generally you can probably increase their basal-bolus by a certain percentage, maybe lean more towards the bolus to get more of a 40/60 split.

If you’re using prednisone on top of a basal-bolus regimen – someone that’s on a basal-bolus regimen, then yeah, you could add NPH on top of that basal-bolus regimen.  That’s exactly right.  So someone that has new hyperglycemia, is not on insulin currently, they start to have hyperglycemia when they start the prednisone, then you would just use NPH.  If they’re already on a basal-bolus regimen, they’re having more hyperglycemia that you feel is due to the prednisone, then you could add NPH on top of that.  Correct.  You could also switch to NPH BID as well.  But certainly it could be easier to add that NPH, because then when the prednisone stops, you could just take away the NPH.

FLYNN:  Great.  The next question we have is from Kathy (sp?).  She said we are trying to push to be more data-driven with glycemic management.  For COVID and beyond, what metrics or KPIs should we be looking at to begin to make long-term changes and improvements?

MESSLER:  Yeah, great question.  For any project that we do, getting the right data and getting that data out in the hands of the front line and the executives is so crucial.  What’s the key data around glucose metrics?  I think a lot of it will depend on your institution and your goals and what you’re trying to achieve, what you want to cover as your challenges.  Sometimes, the metrics are based on how easy it is to get, whether it’s – we know sites want to know how many of their patients are on basal-bolus therapy when that’s indicated, but that may require a chart audit, so then they don’t have that metric.  But if you’re able to do things without audits – so sometimes, it’s just simply ease.

But in general, the guidelines are going to be you’re going to want some outcome metric, so what’s your primary focus – hypoglycemia reduction and make sure you have balancing hyperglycemia reduction?  Some process metrics, so that may be how you’re ordering.  It may be how you’re initiating basal-bolus therapy, that you’re making changes.  And then certainly those balancing metrics.  So being clear that you have some outcomes, process metrics, and balancing metrics, being clear on that question that you’re asking, and sometimes the data that you get is unfortunately limited to the data that you can get – what you can get out of your system.  That does make it often a challenge.

We try to strive here at Glytec to get a variety of metrics out around hypo-, hyper-, in range, and then getting some added process metrics as well to help recognize how you’re managing insulin to improve care.

FLYNN:  Great.  The next question we have is from Ed.  He’s saying other than the CGM example, are you seeing any other changes in practice or protocols that were made due to COVID that you think should remain in place post-COVID?

MESSLER:  Yeah, good question.  I highlighted a few of them.  I think the main one that I’m hearing from sites that’s relatively simple that should continue is that bundling of care – to really monitor the workflows of our nursing and techs to help manage blood sugar.  It is a bit cumbersome.  And multiple people coming in and out, doing blood sugar checks, delivering meals – really trying to bundle care so you limit the amount of motion and limit the amount of entries.  So the goal is reducing entries in the room, but that’s certainly a great goal as well to improve efficiency.  So I think bundling of care better and looking at how to be more efficient in managing is certainly key. 

There may be some other protocols that have developed to help stratify care.  We’ve seen some sites do that to have sort of a higher priority in certain situations or really adjust their metrics for when they’re starting IV or subQ insulin.  I think better protocols, more clarity, and really trying to find that you can individualize.  One thing that we do at Glucommander is recognizing that there’s a variety of different patients with hyperglycemia, and to be able to individualize care based on renal disease or nutritional status, other factors is important.  So protocols that have been able to individualize a little better – those should certainly stick.

FLYNN:  Great.  I think we have time for one more.  This question is from Joe.  He said talking about some of these new technologies, do you foresee any of them becoming the standard of care in the near future?

MESSLER:  Great question.  I think that insulin management is such a challenge and fraught with issues.  We have a lot of places that continue to use paper protocols, protocols that have not been updated in a long time, protocols that – we call them paper protocols, but maybe have made their way into the EMR.  They’re still basically paper protocols.  So you’re asking our nurses to manage complicated medications with calculations, with multiple columns, either doing math or multiple steps.  And we know that there’s so many priorities, particularly in the ICU setting, that they should be able to comfortably manage IV insulin without having to do multiple steps or calculations.  So certainly having insulin management software like we have here at Glytec with Glucommander – I’d be hopeful that that’s the standard of care one day to really minimize those calculations and reduce that cognitive load burden on our frontline workers and safely manage insulin in our patients.

FLYNN:  Great, thank you so much.  I think that is all the questions that we had in.  If there are any others, please feel free to still enter them in, and we can follow up with you directly after the webinar.  Otherwise, it looks like that that’s all the time we will have for today.  Jordan’s information is up on the screen.  Please feel free to reach out if you would like to speak with a member of our team, or again, if you do think of any questions after the webinar today.

And then we’d just like to say thank you on behalf of everyone at Glytec, and we hope you all have a great rest of your day.

MESSLER:  Thanks, everyone.  Take care.