Anne Peters, MD, Keck School of Medicine of the University of Southern California

For what it’s worth, I interview a lot of doctors. I’ve done a lot of panels. What struck me about you folks—the folks who deal with diabetics every day, or people with diabetes—I’m informed that diabetics is not the best term.

Not good—so, people with diabetes, people dealing with this disease. What I noticed is that you listen. Every 1 of you talks about listening to people. Doctors are bad at that, as a group, but not you. Did you select this because you like listening, or did you learn to listen because that’s what you do? I don’t know. It was just an observation. Call it a hunch. Look, we have come to the end of this discussion, but I don’t want to leave without giving each of you an opportunity to say something that you feel we may have omitted or something that you want to leave our audience with. Why don’t we go around, and each of you can take about 30 seconds and give us some final thoughts. Why don’t we start with you, Elaine?

 I’m just thinking back on the patients that I saw today. One of the biggest challenges of diabetes, and dealing with highs or lows, is that you could do everything perfectly Monday to Monday. With other things like saving money, or training for a marathon, you have something to build on. Maybe on the eighth day you can take a day off. That’s not the case with diabetes. You’ve got to start all over again that eighth day and do it all over again, and it may be the worst day of the eight. It’s such a marathon to run, and you don’t have an end line, or point, to look forward to. As a provider, you have to place yourself in that reality. You have to see through the patient’s eyes every day, and if you don’t do that, then you won’t understand their struggles and you miss the boat. That’s what I strive to do every day for them.

Wow, that was well said. Thank you. We really need to understand that, as Elaine has said, diabetes never gives the patient a break; it’s 24-7. Hypoglycemia is incredibly scary and really does limit so much of what the patient can and can’t do if we aren’t careful with educating our patients, assisting with quality of life, and making sure patients have a good understanding of their medications. We need to provide good education on prevention and treatment, and the use of continuous glucose monitoring [CGM] to try and help patients prevent hypoglycemia. We all need to take it seriously and make sure that we ask the right questions every time we touch the patient, so that hopefully we can have a better outcome for them.

I’m going to say something completely different, but I agree with what Elaine and Davida said. I want a system in which the pharmacist tells the patient and me every 2 years when their glucagon is going to expire, so I know to write a new prescription. Because what makes me crazy is when I’ve forgotten and the patient has forgotten to ask, and then they have a bad low and they don’t have their glucagon. Why can’t the pharmacists do this? I get bugged all the time about everything. Why can’t the pharmacist just say, “Patient X needs a prescription for glucagon”? That’s no skin off my back. They should probably just do it without a prescription. Why does this even have to require a prescription? That’s another issue. We need a system so patients and providers are reminded to do the refills. I don’t know why it doesn’t exist, so we need to create that solution.

Could that be built into the EMR [electronic medical record]?

When you click the prescription, it should pop up in 2 years.

 It should just say, “This is due.” Why not?

Jay Shubrook, DO, FACOFP, FAAFP, BC-ADM: 

Hypoglycemia is certainly something that’s very important to our patients, and most providers underestimate the frequency of it. Please ask your patient and the family at every visit about hypoglycemia. There’s no better time than today because we have plenty of tools to identify hypoglycemia, such as CGM, or continuous glucose sensors. We have ways that we can help patients have less hypoglycemia—particularly patients with type 2 diabetes—with novel therapies, and we have very effective treatments that can abort a hypoglycemic episode. Making sure you use the right treatment at the right time really is going to empower your patients not to be paralyzed by hypoglycemia but to be an informed and active crusader to prevent it and treat it earlier.

I want to thank all of you for being with us. This has been eye-opening for me because I don’t treat diabetes on a daily basis. I always thought, “It’s about sugar, for sure; usually it’s about hyperglycemia.” This hypoglycemic problem is real, significant, and tricky. These new therapies that I’ve learned about from you are strikingly interesting. Thank you all for being here.

I want to thank all of you at home for watching this 

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Thought leaders in diabetes provide closing remarks about the importance of continuous awareness of glycemic control in patients as well as the need for effective communication between patients and providers. 

Final Thoughts: Awareness and Communication in Diabetes 

 We’re talking about physician awareness, and we’ve been talking for the past few minutes about the various new therapies out there. Of course, for patients, I don’t think there’s any disease in which patients are as involved as a copartner in the disease management as diabetes. What do patients need to know about the risk of hypoglycemia with the various diabetic therapies, Jay?

You’re absolutely right: 95% of diabetes treatment is self-management, so the patient drives the ship. We give them tools and information. Part of that is raising awareness that hypoglycemia is unfortunately something that can occur, but it’s not universal and it’s not always severe. It’s important to know that you have to check to know when your glucose is low, so we can properly treat you, and that we have different types of treatment for different types of hypoglycemia. Knowing the 15/15 rule would be very important. Now, we have good choices for outpatient treatment of severe or level 3 hypoglycemia that we can individualize to the person. That’s part of the education.

So much goes into diabetes management that we really need a lot of touch points. If you’re in primary care, you don’t have to go alone. You don’t have to do all this. Involve any other specialists they’re seeing—whether it’s endocrine, diabetes education, a pharmacy team, or a nurse educator. Remember that every touch point is a chance for us to make sure we know what’s going on, and the more touch points, the better someone is going to be managed. By doing team-based care, we’re going to get more information, because if they only see me once every 3 months and the day after they see me they have a severe hypoglycemic episode, they’re not going to remember that 3 months later if they didn’t have an adverse outcome. Those other touch points are critically important.

 I remember giving a talk to the [American] Association of Diabetes Educators. There were 3000 or 4000 of them in a room, and I was struck by the fact that doctors sometimes don’t have a clue that this is a team—that the educators are there to help, the pharmacists are there to help, and the diabetic nurses are there to help. How do you get this team organized? Does every family care physician need to be integrated into this kind of a team, or is this for you guys, the specialists? Davida?

Well, you must constantly be talking. If I see a patient, I make sure my chart goes to whomever else the patient is seeing, whether it’s cardiology, the pharmacy, or whomever. You do a cc, do an In-Basket message. I was talking today with cardiology because we were trying to persuade a patient to take a statin, and we wanted to be on the same page. I’m making sure that I tell the next person in line, just as Jay said, that this is what I prescribed, this is why I prescribed it, and I ask, “Can you help me with education of the patient to make sure they understand why we want to do it?” It’s really important that the right hand talks to the left hand and that we constantly work together and that we give the same message to that patient. I don’t have to know all this stuff. I don’t have to be the only 1 who does it, but I do need to pass off to my team members so we can help that patient. Make sure nephrology, ophthalmology, and all the other team members are involved. 

 It’s easy to say that from the perspective of you folks who are specialists and deal with diabetes every day, but on average—it seems to me—primary care physicians have everything coming through the front door: heart disease, diabetes, eczema, you name it.

Is it reasonable to ask that PCP [primary care provider] to have this diabetes team available at his or her fingertips to integrate the patient into it from day 1?

That’s why they use a specialist. That’s why they use an educator or nutritionist, so they can take the piece that’s appropriate to them and then pass it off. That’s why many primary care physicians, once the patient is on multiple daily injections, would prefer a specialist to manage that patient. I don’t want to take care of sore throats and ears. I want them to have a primary care provider that wants to manage those things and a cardiologist. It’s not that we want to live in our own little box. We want to share and make sure that everyone knows what’s going on with the patient. In primary care, as specialists, we should be helping them with these things and making sure they know that there are diabetes educators available, that there are clinical pharmacists available, and that there are dietitians available who want to support them in what they’re doing with diabetes.

 It sounds like you have to make 10 phone calls, right?

 I’d like add something to that. Every person with diabetes has a diabetes team. It is just a matter of who’s on that team. Most people with diabetes are managed in primary care, but that doesn’t mean they don’t have a team that’s helping them. It might be that there are family members, a community leader, or a friend. I ask, “Who’s on your diabetes team?” If they don’t know what that means, then I might actually say, “Do you also see an endocrinologist? Do you also see an ophthalmologist? Do you see a nephrologist? Do you see a podiatrist? Do you see a dietitian? Have you had other forms of education? Do you work with other people at work or at home on your diabetes?”

That raises awareness that this is a lot of work, and we utilize different resources, depending upon what the needs are. Everybody must have a team approach to this. Having done both primary care and specialty care, I put the onus on the primary care practitioner to send the first letter saying what I would like help with, because when I send that first letter, then I’m surely going to expect a letter back saying, “What did you find?” Too often, we don’t send the letter the first time, leaving it unclear what the consultation is supposed to be. My message would be start the process and the communication from the get-go.

OK, but let me ask you, what is this letter? Who’s sending it and who’s it going to?

If it’s to another health care provider, the primary care provider is sending it to whomever they refer the patient to. If it’s team members in the community, then of course you aren’t sending a letter. You might say, “Why don’t you invite them to your next appointment? Because if they’re able to help you, then I want to make sure you’re getting all the help you need.” Knowing key players in that person’s health care plan is really important.

We’ve been talking about all these experts who are weighing in to take care of this patient. How important is the education of the patient themselves, to deal with this and to understand what’s being said and to make choices and selections, Jay?

Diabetes is 95% self-managed, so we have to give people the tools so they know how to make decisions. Surely, there are several thousand minutes in a year, and most patients might only have 60 minutes with us, so that means they’re on their own more than 8000 minutes per year. We have to make sure we give them the tools to make decisions. This group knows very well that only a minority of people get proper diabetes education in the first year, which really prevents them from being able to make smart decisions. We have to go through a lived experience, which sometimes can be painful.

I used to say to my patients, “I don’t go home with you at night, and that’s a good thing for both of us. So I need to equip you with the education you need to feel comfortable about managing your diabetes.” If the patient calls and says, “You’re going to be upset because I made changes in my medication,” I say, “No, if I’ve done my job right, you feel comfortable doing that and informing me of what you’ve done and knowing when you can call or you should call for assistance if you need it.” Diabetes is a disease that requires self-care. We must arm the patient with the right education, the right tools, and the right knowledge. Family members need to be as well educated. I love doing a video visit when all the family members come in to help, and it may be the first time I’ve ever met all family members, so you get that input. The patient is in the driver’s seat with diabetes, definitely.

 There are 2 problems that are very specific. One is people who have recurrent episodes of severe hypoglycemia or significant hypoglycemia unawareness. Those are people who need to be referred to a diabetes team specifically because there are educational programs that exist to work with patients to help them get their blood glucose levels above 100 mg/dL and keep them above 100 mg/dL, so that it restores hypoglycemia awareness. There are very specific approaches to restoring awareness that are very important for those patients who have recurrent episodes of level 3 hypoglycemia or even level 2 hypoglycemia.

The other problem is perhaps something only we endocrinologists see. I see patients who cling to being low because they’re so afraid of being high and getting complications. It becomes a psychological disorder—they may deal with anxiety or even OCD [obsessive compulsive disorder]. Whatever it is, it’s not something I can fix just by telling the patient, “Take 1 unit less before lunch.” It’s a psychological problem that actually requires that patients get therapy, mental health help, and work through their issues, because I want people to feel comfortably safe and in a normal zone. If they want to be too low too often, that’s also a real problem we’ve discussed. We need to think about the psychosocial aspects for certain patients who may need psychological help, and then the notion that there are programs and approaches for people who have recurring, real lows.

A panel of experts in the treatment of diabetes discusses the importance of self-management of blood glucose levels and emphasizes the need for multidisciplinary care teams and referrals for optimal disease management. 

A Multidisciplinary Approach to Diabetes Management 

 Let’s talk about patient factors. We alluded to it, but let’s make it a bit more concrete. What are the patient factors that you consider when you’re talking about the injectable treatment vs the nasal spray? Let’s take the red kit out for now because I’m getting a sense none of you guys really likes that very much, but it was all you had for a while. Let’s look at these 2 new therapies: the injectable and the intranasal. Are there some patients who are better off with 1 rather than the other? If they like 1 or the other, can you switch from 1 class of therapy to another? Elaine?

Absolutely. You could definitely switch, but we’re not really talking about a patient but who’s going to be administering it. I don’t know that patient factors really matter as much as looking around and seeing who might be attending to that person is: spouse, nursing aide, coach, roommate, or teacher. 

I shouldn’t have said patients. I should have said sociologic factors because that’s the whole environment, right? It’s the whole ecosphere.

 What Davida said was also really important: insurance coverage, at the end of the day, is going to make a difference too. It makes a big difference for all of us. Look, we don’t get too picky around basal and bolus insulin. We usually just go by what the insurance tells us to prescribe. That’s often the way medicine works these days. We say, “We are going to use growth hormone, so we must look at the insurance. We’re going to use this or that or the other.” We are going to look at the insurance first. It’s part of being an endocrinologist. It’s really all the same in the end. It’s the brand we use or what the insurance tells us to use. Unfortunately, that extends to glucagon products. Luckily, as Davida also mentioned, usually 1 or the other is covered.

Is it fair to say, from what I’m hearing, that it’s in the “do not care” mode? They both work; they’re both efficacious. If insurance covers 1, just buy that 1. If insurance covers the other 1, buy that?

 Personally, the form factor is important: the prefilled syringe and the pen-like device is more familiar to patients with diabetes than the intranasal and injection. I have children who haven’t received the full dose of the intranasal glucagon when they’re seizing because they’re hard to control.

In other words, it’s what you pointed out before. If a kid is writhing or moving around, it’s tough to put something in that kid’s nose and get the whole dose in there.

You put it in, and they suddenly jerk, and you don’t know if they’ve got it and you’ve already used 1 Baqsimi a month ago. Then what do you do?

 I hear what you’re saying. You like the SC [subcutaneous] version better.

 Can we take a vote? Who likes what? Why don’t we go around the horn a little. Davida, what do you like?

 I agree. I tend to like the prefilled forms of this, only because it reminds people of an EpiPen. It’s easier to find a body part to be able to put it in vs having to get it in the nose.

 I’m sorry, you just reminded me—pick a body part, any body part. But it makes sense—

I heard that it hurts, that the intranasal spray really hurts. One family used it a little prematurely, and the patient wasn’t truly unresponsive yet, so they said it was the most painful.

 Really? We didn’t discuss this—the intranasal hurts?

 I haven’t heard that, but most of my patients are unconscious when I get it, so I’m not sure that counts.

This poor child wasn’t quite unconscious yet, and it hurt.

Patients and family members are just grateful for using either of those as opposed to the panic when they open the red box and say, “Now what do I do?” That’s when the 911 call usually happens.

 My patients’ caregivers or family members generally prefer the intranasal glucagon because they’re used to putting nasal spray in because their sinuses are bad or whatever. That’s something they relate to. I don’t have that many family members who are used to giving epinephrine, so they tend to prefer the intranasal method. But it’s not about me; it’s about them.

 I offer it, and I have samples. I ask, “Which 1 do you want?” We also talk about insurance coverage, but if the world were neutral, it’s simply what a family member wants.

I’ve shown people both, and they take whatever they want because it’s about using it. I’ve had patients give it to themselves—the intranasal stuff—and they say it feels like a bullet to the brain. You don’t want a conscious person using glucagon intranasally because it’s a very strong drug and a very strong push-up. But it’s working. It’s really spraying that stuff in the back of your nose. Don’t use it for conscious patients. That’s not a good thing.

 My thought is that after everybody has had a year of having tongs put up their noses for COVID-19 tests, we could all be desensitized to this. Jay, what do you think?

I’m agnostic. I feel like it’s whatever you’re going to fill, whatever the family is comfortable giving—that’s what I’m going to write. Because I treat both adults and kids, it’s all over the map in terms of the response. I need them to have confidence that they can give it, that they can afford it, and that they will fill it. I’ll use any of them because when used properly, they can all work.

 I want to thank all of you at home for watching this 

Key opinion leaders in endocrinology provide an overview of factors to consider when selecting or switching intranasal and injectable glucagon including ease of administration and patient preference. 

Selecting or Switching Formulations of Glucagon 

I want to explore the cost savings in terms of avoiding an emergency department [ED] visit. If someone is seizing—if someone is severely symptomatic from hypoglycemia and you rescue them—with glucagon, can they just stay home? Should they go to the ED or to a doctor’s office after to be sure everything is stabilized correctly?

Let me tell you what the package insert says. The package insert advises caretakers and patients to call 911 and administer glucagon. It’s sometimes hard for people to determine what they should do. If somebody is panicking and they want to call 911, I’m not going to stop them, but there are a lot of cases that don’t require that. It does depend on the comfort of the person present. For older adults it could be more complicated because they could have some sort of cardiovascular event; they may be on a sulfonylurea. In those cases, it may be harder to determine what to do. 

I tell people these things that are true: First, it takes 13 minutes, from when you give the old red kit to someone to have them reach a glucose of 70 mg/dL or above, to start getting better. That’s a long time, and everybody thinks the intranasal glucagon is faster. It’s not. It’s 3 minutes slower, so it takes 16 minutes to take effect. The person is standing there after giving the glucagon—all these, by the way, you can give again if the person does not wake up—but 13 minutes seems like an eternity when someone you love is not right. I tell people to busy themselves doing the right thing. 

First, you don’t want that person on a chair or somewhere—probably they had fallen over anyway, but I want them to be comfortable on the floor lying down, so when they wake up they don’t freak out. That way, it’s peaceful. A lot of times when people wake up they feel nauseated; they may vomit; they may have a headache. They’re not going to feel great, having just had glucagon. While you’re waiting for the person to wake up, get a towel, get a little water, maybe get a little bucket in case they throw up—make it just peaceful and gentle. I get the caregiver to be involved and not flip out because you just want a calm caregiver, but you cannot always guarantee that. The package insert does say to call 911, but I help people try to differentiate between what’s sensible and what’s not, but that’s always the default. I don’t want to take that away from scared family members.

Sure. It occurs to me you could also have, as a consequence of hypoglycemia, cardiovascular effects or hypotension. You could even have an infarct. You could have a stroke. The downside of going to the ED is that the cost saving is no longer there, and it’s always a madhouse at the ED. It does make sense to at least consider that, and the 911 recommendation seems to confirm that, yes?

Yes, but the paramedics can also assess. If the paramedics get there and the person is waking up and they’re doing fine and they just want a sandwich, then the paramedics will not transport them. There’s an assessment that the paramedics do, but I’ve had patients, especially older patients, who take a really long time to recover. Even I can’t tell if they’ve had a stroke or not or what else is going on, so if you’re in doubt, get help. Because I’m not asking the family—

They can get vitals and do the neurocognitive assessment and all the stuff that caregivers can’t necessarily do.

Yes, and you don’t want that to be the responsibility of a caregiver. Caregivers don’t want to make a mistake, so that’s why I never tell people, “Don’t call 911.” If they’re comfortable and this has happened before, if they know what to do, then it’s OK. Then they just need to be prepared that that person isn’t going to feel great when they wake up.

There’s a study out there, right? There’s a phase 3 crossover study looking at the efficacy and safety of subcutaneous glucagon for hypoglycemic rescue in adults with type 1 diabetes. What’s the study looking at? Is it a good study? What are the implications of the trial data to the clinician and to patients? Anne, do you want to walk us through that a bit?

Sure. The studies they did—the phase 3 studies—were just to look at noninferiority. The good news is that it’s hard to recruit for these studies because you have to get patients who are having recurrent episodes of severe hypoglycemia. My inclination is to try to prevent those from happening, not just have people in the who you watch. But in the studies where they’ve done it and they’ve been able to compare it with inhaled glucagon or intranasal glucagon vs the stable soluble subcutaneous glucagon, they’ve shown noninferiority. As I said, it takes a little longer with the inhaled nasal glucagon than it does with the SC [subcutaneous] glucagon. The comparisons are fine. They’re noninferior; they work. 

What’s more interesting to me than the phase 3 crossover trials is the usability studies. The usability studies showed a very low rate of people being successfully treated for severe hypoglycemia with the traditional reconstitution-requiring kit and a much higher rate of success—both with trained caregivers as well as untrained caregivers—with the intranasal glucagon and the stable soluble glucagon. That’s what matters to me clinically. Are people going to use it, and are they going to be successful? The answer is yes, so I’m sold. I don’t have any doubt that these agents work, that they work well, and that they work better because they’re used.

You know, there’s an analog in the hospital for malignant hyperthermia, which is dantrolene. It’s several vials of a powder, which has to be available and reconstituted. It takes a team to start mixing the stuff up. I can’t imagine doing that in somebody’s home. It sounds much easier to use an EpiPen-like device or a nasal spray. There’s no mystery here.

You asked another question, Peter, about if should they call their health care provider when they have an episode. That’s a really important comment or question. Once a patient has had an event with low blood sugar, we do want them to let us know because we want to problem solve while they can think through it and it is fresh in their brain as to what happened and what kind of education we might be able to provide that could prevent it in the future. We want to make sure they fill a prescription to get glucagon at home. It’s really important that they call us. 

That harks back to what we were discussing earlier, right? It is part of long-term monitoring.

You need to be gauging these people for a long-term plan for controlling this. If it’s a 1-off, maybe, but it happens all the time, you need to know about it.

This is right up Jay’s alley. You were talking about that, right, Jay?

Thought leaders in diabetes discuss challenges of insurance coverage for new formulations of glucagon and comment on the potential for long-term cost savings due to decreased overall healthcare system utilization. 

Anne Peters, MD, Keck School of Medicine of the University of Southern California

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