Objective: To prevent medical complications of severe hypoglycemic emergencies, prompt and reliable rescue intervention is critically important. A ready-to-use stable liquid Glucagon Rescue Pen (GRP; Xeris Pharmaceuticals) auto-injector was evaluated for the rescue treatment of severe hypoglycemia.

Method: Two Phase 3 randomized, controlled, blinded, crossover studies were conducted in 161 adults with T1D to compare 1 mg doses of GRP versus Glucagon Emergency Kit (GEK; Eli Lilly) for the treatment of insulin-induced severe hypoglycemia. Efficacy was evaluated as either a return of plasma glucose (PG) to >70 mg/dL or increase in PG ≥20 mg/dL from a baseline PG <50 mg/dL, within 30 min of dosing.

Result: Subjects treated with GRP (98.7%) achieved successful PG recovery within 30 minutes, and (99.4%) had a PG > 70 mg/dL or neuroglycopenic symptom relief within 30 minutes, both comparable to GEK. From glucagon dosing, the mean time to achieve PG >70 mg/dL or increase in PG ≥20 mg/dL was 13.8±5.6 min for GRP and 10.0±3.6 min for GEK. This mean time does not account for the significantly shorter (p<0.0001) drug preparation and administration time for GRP (27.3±19.7 seconds) vs. GEK (97.2±45.1 seconds). The GRP was similar to GEK in terms of glucose Cmax, Tmax, and AUC(0-90min). The overall incidence of treatment emergent adverse events (TEAEs) was comparable in both groups; the most commonly reported TEAEs were nausea (GRP 29.9%, GEK 22.9%) and vomiting (GRP 16.1%, GEK 9.6%). One SAE was reported in these studies (GEK).

Conclusion: A ready-to-use, easy two-step administration GRP achieved plasma glucose recovery reliably, was therapeutically equivalent to GEK, and had an incidence of nausea and vomiting comparable to GEK. There was a significant difference in drug preparation time in favor of the GRP. These results demonstrate that GRP is an effective, safe, and well tolerated rescue treatment for severe hypoglycemia and is a viable alternative to GEK.

Disclosure

M.P. Christiansen: Research Support; Self; Abbott, Biolinq, Dexcom, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Medtronic MiniMed, Inc., Novo Nordisk A/S, Sanofi-Aventis, Xeris Pharmaceuticals, Inc. M.J. Cummins: Employee; Self; Xeris Pharmaceuticals, Inc. S.J. Prestrelski: Employee; Self; Xeris Pharmaceuticals, Inc. M.K. Junaidi: None.

© 2019 by the American Diabetes Association.
2019
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.