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New delivery options could make glucagon administration easier for people with diabetes, caregivers
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New delivery mechanisms in the works for the administration of glucagon during a hypoglycemic event could make the process easier for people with diabetes, particularly children, and their caregivers.
“The advent of self-administered low-dose glucagon will change the treatment of hypoglycemia significantly,” Janet B. McGill, MD, Endocrine Today Editorial Board Member and professor of medicine and director of the fellowship in endocrinology, diabetes and metabolism at Washington University School of Medicine in St. Louis, said in an interview. “Patients and health care providers will need to learn when and how to administer it, how long it lasts and other important factors, like whether carbs are needed in addition to glucagon.”
Alternatives needed
McGill said some inroads have been made in reducing the frequency of hypoglycemia because of analogue insulins, newer therapies for type 2 diabetes that do not cause hypoglycemia, and continuous glucose monitoring. Still, the options available once a hypoglycemic event occurs quickly become limited. Carbohydrate ingestion is a treatment option only if the person with diabetes is awake and alert, has a carbohydrate source available and recognizes the low glucose level early enough for the carbohydrate to take effect before glucose drops even lower.
“There is also a risk of overshooting by taking in too much [carbohydrate], which is difficult to determine in the middle of a hypoglycemic event,” McGill said.
A 2017 study of 89,236 hypoglycemic episodes from the National EMS Information System found that glucagon was underutilized in an outpatient setting and stated that “glucagon use could reduce the number of severity of hypoglycemic episodes requiring medical attention and hospitalization.”
Glucagon kits, however, can be cumbersome and time-consuming to administer, particularly when they require another party’s assistance. Kits require multiple steps to reconstitute powdered glucagon to a liquid form, to measure the correct dose and administer therapy via injection.
Automatic activation
One solution in the works is a “smart” drug — a synthetic form of glucagon that would remain in the body and automatically activate in response to a drop in blood glucose. Matthew Webber, PhD, assistant professor of chemical and biomolecular engineering at the University of Notre Dame, was recently awarded a $1.625 million American Diabetes Association Pathway Accelerator Award to fund a 5-year research project focused on creating a glucose-responsive synthetic glucagon to provide an extra layer of safety for people at risk for hypoglycemia. Webber said he hopes to draw on his postdoctoral training, which included developing synthetically modified insulin that modulates and corrects blood glucose levels.
“There remains a need broadly across the field of drug delivery to enable drugs to function only at the time and place when those are needed,” Webber told Endocrine Today. “In diabetes, this means making sure hormones like insulin and glucagon are made available and are active only at the times when glycemic state dictates a need.”
Webber and colleagues will study different chemistries and protein activation methods to create a smart drug benefiting individuals who experience severe hypoglycemia and nocturnal hypoglycemia. Delivery methods are to be determined and “would depend on glucagon stability, the final device form-factor and the duration of availability of the therapy in the body once administered,” he said.
Nasal delivery
Another solution, still under FDA review since its July 2018 application, is a nasal glucagon under development by Eli Lilly. As previously reported by Endocrine Today, nasal glucagon delivers glucagon as a dry powder spray in a compact, portable, single-use, ready-to-use device.
“Nasal glucagon will be for all with diabetes at risk for [hypoglycemia],” Larry C. Deeb, MD, a specialist in pediatric endocrinology at Tallahassee Memorial Healthcare, Florida, told Endocrine Today. “That is the beauty. All [can use nasal glucagon] since it is so easy to use.”
A person experiencing hypoglycemia or a caregiver simply inserts the tip of the device into the nostril, pushes the bottom and dispenses the powder. Perhaps most importantly, there is no need to determine a dose based on patient weight.
“After dosing studies, it became clear one dose works in adults and [pediatric patients],” Deeb said, adding that he is excited by the potential of the spray. “It was just so simple and easy to teach,” he said. “People easily can do it with almost no training.”
More opportunity
Although self-administered glucagon will have limitations, McGill said, ultimately it “promises to rapidly change the way we approach low or declining glucoses and will add another layer of safety for patients who take insulin.”
Webber expressed optimism also.
“The standard of care and quality of life for diabetic individuals will continue to improve as researchers continue to focus efforts on this complex and life-changing disease,” Webber said. “At the same time, I also look forward to a day when type 1 patients will have access to a robust and lasting cure that will make new technologies for better disease management unnecessary.” – by Amanda Alexander
Reference:
Kahn PA, et al. Ann Intern Med. 2017;doi:10.7326/M17-2222.
For more information:
Larry C. Deeb , MD, can be reached at lcdeeb@deeb.org.
Janet B. McGill, MD, can be reached at jmcgill@wustl.edu.
Matthew Webber, PhD, can be reached at mwebber@nd.edu.
Disclosures: Deeb reports he conducts research and serves on an advisory board for Lilly. McGill and Weber report no relevant financial disclosures.