Benefits of New Formulations of Glucagon

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Experts in endocrinology build a discussion on new intranasal and injectable formulations of glucagon and discuss their benefits compared to glucagon kits that require reconstitution.

Peter Salgo, MD: What are the available glucose-elevating agents out there for the management of hypoglycemia, other than sugar and other than food? How do they work? Let’s talk about glucagon first. The injectable glucagon, which is given SC [subcutaneously]. What have we got out there? Are there any more options? What’s going on here? Anne, do you want to start us off?

Anne Peters, MD: Sure. In the old days, we had what I call the “red kit.” It wasn’t always red, but it was glucagon that required reconstitution. That meant that the human being who had to give the glucagon had to open the kit, figure out how to make a diluent into the powdered glucagon, mix it up, pull it out, and then give it to somebody. For my adult patients, their family members may not be used to dealing with syringes or anything injected, and that’s daunting—so daunting, in fact, that it rarely worked. Now, if you gave that glucagon to somebody having a severe low [blood sugar], it basically always works. Glucagon works.

The problem with that reconstitution-requiring glucagon is that it wasn’t usable by the people who were trying to treat the person with diabetes. Fortunately, recently, we’ve had the advent of 2 ways to give glucagon. These forms of glucagon do not require reconstitution, refrigeration, or anything else fancy. One is intranasal glucagon, where you just basically have to take the little canister, open it up, stick it up someone’s nose, and push on it, and it works. There’s also now stable soluble glucagon that comes in a pen, like an EpiPen, that’s incredibly easy for someone else to give. We’ve basically developed, and have on the market, 2 ways to give glucagon. If you ask me, other than insurance, there’s no reason somebody shouldn’t have 1 of these easier-to-give glucagon tools. Why make it so hard and so impossible when we have a simple approach now available?

Peter Salgo, MD: Am I understanding? I’m hearing that these things are expensive—the new stuff. Yes?

Anne Peters, MD: They’re expensive, and they’re also often not covered by insurance because, as far as I can tell, insurance companies don’t seem to recognize that if I’m not calling the paramedics to transport a person to the hospital, that’s saving a lot of money if you can just use these slightly more expensive forms of glucagon. But if your insurance won’t cover it and you can’t afford to pay out of pocket, there are coupons and things for the cost and the lack of insurance coverages.

Peter Salgo, MD: That’s where I was going. Insurance companies tend not to want to pay for things that cost a little more, and they tend to have these things in silos, right? It costs more, so we’re not going to get it. But they don’t see the cost saving on the other side.

Elaine Apperson, MD: In South Carolina, we have good coverage. We have Baqsimi for commercial and Medicaid coverage. Just last week, I spoke to the Medical Care Advisory Committee [of the Department of Health and Human Services] for their formulary, and we were able to move the Gvoke HypoPen and the prefilled syringe to the preferred Medicaid drug list. I was just explaining to those people that anybody with diabetes is familiar with the syringe and with the pen, essentially. When you’re in a crisis or in a chaotic moment, reaching for a syringe or a pen to bring your child or loved one out of a seizure or an unresponsive state with relative ease and comfort means everything. As Anne mentioned, avoiding a trip to the ER [emergency department] or a ride in EMS [emergency medical services] makes a big difference. Those sorts of things—we look at them and say, “They went to the ER—whatever.” That’s a big, traumatic moment for a child and a family or any family and any patient at any time. Plus, there’s the cost savings. I’m optimistic that, over time, if insurance companies, Medicaid plans, and Medicare plans start looking at the numbers and at the cost savings in terms of the uptake of utilizing these new glucagon forms, something good could happen. All it took was finding a way to make glucagon stable as a molecule in an aqueous solution. That was a challenge for so many years, then finally, for people who were trying to work on glucagon and insulin pumps that contain both agents, we figured out a way to make it stable in an aqueous solution. That’s why we’re able to break through with these new products. It’s a whole new ballgame, and it’s so promising with all our patients with diabetes.

Peter Salgo, MD: I suspect the answer is going to be linked to personal preference, but what patient factors do you consider when you recommend either SC glucagon or intranasal glucagon to have around the house for emergencies? Does anybody want to jump in on this? Jay, what do you think?

Jay Shubrook, DO, FACOFP, FAAFP, BC-ADM: The other thing about cost that we need to highlight is that I’m happy if I write a glucagon prescription and it goes unused for a year. They must be renewed, and a lot of people don’t want to renew something they did not use, especially if they’re paying for it, but this is a lifesaving medication. We wouldn’t ask people not to refill their EpiPens, so we need to liken it to that. These are flat priced in my neck of the woods, so I give the patient a choice. These are the 3 ways you can give it. I really care more about who the person that’s going to be giving it to you because you shouldn’t be giving it to yourself. Whom do you spend most of your time with? Are they with you at the appointment? These are the 3 ways: You can suspend—make the suspension of the glucagon in the red kit—you can use a single injection, or you can use the nose spray. All these will work when used correctly. Remember, you’re using it in a time of distress, and it’s usually used by someone who doesn’t have experience. Sometimes it’s very clear: Patients will say, “I still want an injection,” or “I don’t want an injection,” or “I’ve used the red kit before, and it worked.” All these are very effective tools, and we need to let our patients and their families and friends have some say in that. That works well.

Peter Salgo, MD: What about schools? Are schools accepting the EpiPen equivalent because they’re accepting EpiPens? Do teachers know how to give it? Or does it stay with the school nurse? Or do the schools back away and say, “We want no part of this”?

Elaine Apperson, MD: Schools are accepting it. I make a bit of a presumption that anybody with a working brain wouldn’t choose the glucagon kit. I basically say these things: “The Gvoke and the Baqsimi are stable for 2 years, and that’s a real plus as well.” I say, “If I were you, I’d probably choose the intranasal or the subcutaneous. Having given a glucagon kit injection or 2 to a big seizing 14-year-old boy, I was panicked. It’s not easy, and I knew what I was doing.” I’m very forthright with my experience and what I see as clinical advantages.

Peter Salgo, MD: Go ahead.

Davida Kruger, MSN, APN-BC, BC-ADM: If you look in electronic medical records too, you can type in Baqsimi or Gvoke, and it will tell you which is preferred. I try to handle it that way. I want it to be the patient’s choice, but I agree with Elaine: I’d really like them to move to something easier. Sometimes they’ll say, “I’ve used an EpiPen, and that looks like an EpiPen, so I’ll take that,” or they don’t have any problems with intranasal. I try to look at the insurance so I can say, “This is preferred.” In Michigan, I’m impressed, since almost all our insurances provide 1 of the newer forms of treatment for the patients. The red kit was never cheap. If you didn’t have insurance to cover it, it was really hard to get it for the patient because sometimes it was $300. That’s coming into play as well. They’re available, and if we remember to tell our patients, we can get better outcomes. I agree with Jay: A lot of times they’ll say, “I never used it before.” I don’t want you to be without it in case you need it, so I try to get every one of my patients to take a prescription and fill it for glucagon. This is the bigger problem, that patients don’t fill it.

Peter Salgo, MD: Right. It’s no good at all if you just have a piece of paper. That won’t work. You can’t give a piece of paper SC. You’ve got to get—I just dated myself. Prescriptions aren’t on paper anymore.

Davida Kruger, MSN, APN-BC, BC-ADM: They aren’t on paper anymore.

Peter Salgo, MD: They’re all digital, right? It’s even worse. It doesn’t do you any good if you hit enter and then somebody doesn’t go to the pharmacy and pick it up.

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Transcript Edited for Clarity