Diabetes Forecast

New Easy-To-Use Glucagon Products Are Coming

Jessica Dean/Mittera

Diabetes is a balancing act, particularly when you take insulin or sulfonylureas. You’re always striving for equilibrium between blood glucose levels and low blood glucose (hypoglycemia). If you do unplanned activity, skip a meal, and/or give yourself too much insulin, the scales can tip. You quickly can develop low blood glucose. Without treatment, hypoglycemia can cause you to have poor judgment or lose consciousness. That means you can’t swallow glucose-containing food or drink to bring your levels back up.

From there, it’s glucagon to the rescue. Another person must mix and inject you with a solution containing the hormone—which signals your liver to release stored glucose into the bloodstream. The multistep process can be nerve-wracking for loved ones, friends, and coworkers.

Caregivers worry about following the instructions properly during an emergency, says David Klonoff, MD, FACP, medical director at the Diabetes Research Institute at Mills-Peninsula Health Services and clinical professor of medicine at the University of California–San Francisco. But the future of glucagon treatment may not be quite so complex—or stressful. Pharmaceutical companies are developing easier, and potentially faster, ways to deliver this life-saving hormone.

Ginny Peck of Lincoln University, Pennsylvania, still remembers the day she had to follow six steps to save her daughter’s life. Seventeen years ago, when her 8-year-old daughter, Mattie, was newly diagnosed with type 1, the two were in the car running errands. They’d been having a conversation when Mattie suddenly stopped responding. When she saw her daughter having a violent seizure, Peck immediately pulled over to give glucagon.

“I was panicked, and yet I knew her life depended upon me doing everything I had been taught,” says Peck. With trembling hands, she mixed up the solution and gave Mattie the injection. Peck says the training she received on how to give glucagon helped her through the experience, but it was hard to perform all the steps while shaking. “Anything that would be faster and require less coordination would certainly be beneficial,” she says.

Researchers have taken strides toward a future where glucagon delivery isn’t a multistep process. They are developing glucagon products that require no mixing—or injection. Their goal? A fast hypoglycemia treatment that lessens a caregiver’s stress during a tense emergency situation—and saves lives.

Testing, Testing

The race is on to bring easier-to-use devices to market. “Until there is a cure for diabetes, and that cure is readily available to everyone in the world who has to take insulin or [sulfonylureas], we need better ways to help people manage hypoglycemia,” says Elizabeth Seaquist, MD, an endocrinologist and professor of medicine in the Department of Medicine at the University of Minnesota. In the works:

Nasal Powder

Eli Lilly and Co.’s intranasal glucagon uses a device similar in size to your typical nasal spray to propel powdered glucagon into the nasal passages, where it’s then absorbed into the bloodstream, says Michael Rickels, MD, associate professor of medicine at the Hospital of the University of Pennsylvania and lead investigator of an independent trial on nasal glucagon.

Benefits: This is a fast, one-step process. Because it’s needle-free, it may be less scary for caregivers and easier to deliver correctly. Like current treatments, nasal glucagon can be given to an unconscious person. “They are not required to inhale or sniff the powder,” says Rickels. “The device dispenses the powder with one push.”

Drawbacks: Previously, some concerns arose about how the nasal glucagon was absorbed from one person to the next—if you had a cold or excess mucus, for instance. But a study presented at the American Diabetes Association’s 2017 Scientific Sessions found that the nasal glucagon had similar absorption in people who had a cold and those without.

Availability: Eli Lilly’s product is currently undergoing Phase 3 clinical trial testing in controlled settings with subjects observed by clinicians and researchers. According to a company spokesperson, Eli Lilly expects to submit for Food and Drug Administration (FDA) approval by the first half of 2018.


Zosano Pharma is working on a patch with a microneedle underbelly. When the needles penetrate the skin, the coating of glucagon powder will enter the bloodstream and go to work.

Benefits: Caregivers may be less nervous about applying a patch than preparing and injecting a solution. It’s a quick and simple (it can be applied to any area of skin), single-step process. Plus, it’s easy to carry on you at all times.

Drawbacks: In theory, the microneedle administration would be slower at getting glucagon into the system than the current intramuscular injection because there is more blood flow in muscles than just under the skin. “But we don’t know how much a difference that makes until comparison studies are done,” Klonoff says.

Another drawback is that the patch will need an adhesive to stick to the skin, which could cause a rash or other reaction. “Though that’s a minor problem compared to severe hypoglycemia,” Seaquist says.

Availability: Zosano Pharma completed Phase 2 clinical trials in 2015 but put further trials on hold in March 2016 to focus its resources on a product unrelated to diabetes. It’s unclear when patch trials will resume.


If all goes as planned, Xeris Pharmaceuticals’ device will work similar to EpiPens and other pens prefilled with medicines, such as insulin and type 2 injectable drugs. The device will contain a stable form of glucagon that’s already dissolved into liquid, says Rickels.

Benefits: Because the glucagon is premixed, the caregiver simply removes the cap and injects it into the person with severe hypoglycemia. The pen would likely push glucagon into the system as quickly as the current syringe kit, says Klonoff.

Drawbacks: Creating potent yet stable premixed glucagon is a challenge. Klonoff says researchers are testing ways to ensure the glucagon molecule is not altered or made less potent when dissolved and stored in liquid.

Availability: The pen is currently in Phase 2 clinical trials, and Phase 3 trials will follow. Xeris expects to submit a new drug application to the FDA in the first half of 2018. The anticipated approval date is a year later.

Order Up

Too many glucagon kits are left unfilled on pharmacy shelves. A 2015 study published in Endocrine Practice found that about half of 8,814 people with type 1 diabetes filled their glucagon prescription, and only 2.4 percent of 47,051 people with type 2 diabetes who were starting insulin filled theirs. Those who did fill their prescription, and did so within the first 1½ months, had a lower incidence of hypoglycemia-related emergency room visits.

How to Administer Glucagon

In the Pipeline

3 promising products for future treatment of hypoglycemia

Scientists are working on more advancements in hypoglycemia treatment. While you won’t see these products soon, they may be a reality in the next three to five years:

Pills for Prevention: Researchers are looking into agents that could be taken in pill form to prevent hypoglycemia unawareness from occurring in people who typically experience blunted symptoms of low blood glucose, says Elizabeth Seaquist, MD, an endocrinologist and professor of medicine in the Department of Medicine at the University of Minnesota and a consultant on Eli Lilly’s nasal glucagon. If you recognize low blood glucose early, you can treat it yourself with glucose tablets or gels instead of glucagon.

Micro Doses: Another avenue of research is the use of very small doses of a glucagon solution to treat mild hypoglycemia. This could be useful when a person is sick and can’t eat, or if they’d rather not eat or drink more carbohydrate, says Michael Rickels, MD, associate professor of medicine at the Hospital of the University of Pennsylvania. This is currently being developed as a pen that you would carry with you at all times.

Dual-Hormone Artificial Pancreas: One of the biggest challenges to a dual-hormone artificial pancreas—that is, one that uses both insulin and glucagon—is developing glucagon that is stable in liquid form and effective for prolonged use, says David Klonoff, MD, FACP, medical director at the Diabetes Research Institute at Mills-Peninsula Health Services and clinical professor of medicine at the University of California–San Francisco. This may require altering the structure of glucagon so that it remains stable but just as potent for a long time when dissolved.

Revised Sept. 26, 2017



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