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Intranasal Glucagon on the Horizon for Diabetics

Product may offer simpler solution to hypoglycemia over intramuscular injections.

The risk of hypoglycemia poses a great risk in type 1 diabetes patients.  Hypoglycemia is characterized as abnormally low blood glucose levels, usually below 70 mg/dL. Some noticeably early symptoms of hypoglycemia are shakiness, anxiety, sweating, confusion, hunger, or headaches. Severe hypoglycemia can lead to loss of consciousness or seizures, which makes treatment of hypoglycemia a high priority. Hypoglycemia is a big concern in diabetic patients due to their tight glycemic control. Studies show that a type 1 diabetic on an intense insulin therapy can be symptomatic of hypoglycemia up to 10 times per week and experience a severe disabling hypoglycemic episode once a year. It is estimated that 2-4% of deaths in type 1 diabetes is due to hypoglycemia. Hypoglycemia is also very common in type 2 diabetics on insulin with prevalence rates of 70-80% in clinical trials.

Severe hypoglycemia should be treated aggressively to prevent major complications. Currently, treatment for severe hypoglycemia outside of a hospital setting is limited to intramuscular glucagon, which requires reconstitution prior to administration. This can increase the chance for error. Eli Lilly is currently doing an investigational study on intranasal glucagon to combat hypoglycemia in a much simpler and safer solution.

A randomized crossover noninferiority trial was conducted at eight clinical centers. The study enrolled 75 adults with type 1 diabetes with the mean age of 33 years old and median diabetes duration of 18 years old. The study did a head-to-head study of intranasal glucagon (3 mg) versus intramuscular glucagon (1mg). The success of therapy was defined as increasing plasma glucose to greater than 70 mg/dL or an increase of 20 mg/dL in plasma glucose after 30 minutes of administration of glucagon.

The research participants fasted overnight and had starting glucose levels of at least 90 mg/dL. The participants were then given intravenous insulin infusions until their blood glucose levels dropped below 60 mg/dL to induce hypoglycemia. Once hypoglycemia was reached, the insulin infusion was stopped and participants were given one of the two glucagon products five minutes later. The intranasal glucagon was administered by placing the device into the patient’s nostril and by simply pushing a plunger by which the device releases the glucagon powder into the patient’s nasal cavities. The glucagon is then absorbed in the nasal mucosa without need for inhalation by the patient. In a previous phase 1 study, the absorption of glucagon through the nasal cavity is not impacted by nasal decongestion.

The study had positive results for intranasal glucagon. Intranasal glucagon successfully treated 74 out of 75 patients versus intramuscular glucagon 75 of 75. The one unsuccessful intranasal glucagon patient came close to meeting the success criteria, reaching plasma glucose of 65 mg/dL after 30 minutes and had an increase of 25 mg/dL in plasma glucose after 40 minutes. The rise in blood glucose in intranasal glucagon lagged 5 minutes behind intramuscular glucagon. The difference of 5 minutes is unlikely to be clinically significant and is offset by the real-world delay of administering intramuscular glucagon.

With the efficacy of intranasal glucagon, if approved, could replace intramuscular glucagon as standard of care. The ease of administration and accessibility of intranasal glucagon makes it a much more practical solution to hypoglycemia. The ease of administration lacks the cumbersome and error-prone steps of intramuscular injection such as reconstitution and injection. Intranasal glucagon could be the future in combating hypoglycemia due to ease of use and effectiveness of the medication.

Practice Pearls:

  • Hypoglycemia occurs when blood glucose drops below 70 mg/dL. Patients should be aware of signs and symptoms of hypoglycemia such as shakiness, anxiety, sweating, or headaches.
  • Glucagon is an effective treatment for hypoglycemia in patients. Currently outside the hospital setting, treatment for severe hypoglycemia is limited to an intramuscular glucagon injection.
  • Intranasal glucagon is an investigational product by Eli Lilly. Rise in blood glucose of intranasal glucagon lags behind intramuscular glucagon by 5 minutes, but is unlikely clinically significant and offset by ease of use of intranasal glucagon.

Rickels, Michael R., et al. “Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study.” Diabetes care (2015): dc151498.

American Diabetes Association. “Hypoglycemia (Low Blood Glucose). www.diabetes.org

Briscoe, Vanessa J., and Stephen N. Davis. “Hypoglycemia in type 1 and type 2 diabetes: physiology, pathophysiology, and management.” Clinical Diabetes 24.3 (2006): 115-124.  


Researched and prepared by Jimmy Tran, Doctor of Pharmacy Candidate LECOM College of Pharmacy, reviewed by Dave Joffe, BSPharm, CDE