Nasal glucagon as a viable alternative for treating insulin‐induced hypoglycaemia in Japanese patients with type 1 or type 2 diabetes: A phase 3 randomized crossover study

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2020-07, Vol.22 (7), p.1167-1175
• Main Authors: Matsuhisa, Munehide, Takita, Yasushi, Nasu, Risa, Nagai, Yukiko, Ohwaki, Kenji, Nagashima, Hirotaka
• Format: Article
• Language: English
• Subjects: Adult; Blood Glucose; Blood pressure; Cross-Over Studies; Diabetes; Diabetes mellitus (insulin dependent); Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2 - drug therapy; Drug dosages; Female; Glucagon; Hemoglobin; Humans; hypoglycaemia; Hypoglycemia; Hypoglycemia - chemically induced; Hypoglycemic Agents - adverse effects; Insulin; Intravenous administration; Japan; Male; Nausea; Original; Pharmacodynamics; Pharmacokinetics; Success; type 1 diabetes; type 2 diabetes; Vomiting
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.14019

Aim To compare nasal glucagon (NG) with intramuscular glucagon (IMG) for the treatment of insulin‐induced hypoglycaemia in Japanese patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM). Materials and methods This phase 3, randomized, open‐label, two‐treatment, two‐period crossover non‐inferiority study enrolled Japanese adults with T1DM or T2DM on insulin therapy, with glycated haemoglobin levels ≤86 mmol/mol (≤10%). After ≥8 hours of fasting, hypoglycaemia was induced with human regular insulin (intravenous infusion). Patients received NG 3 mg or IMG 1 mg approximately 5 minutes after insulin termination. The primary endpoint was the proportion of patients achieving treatment success [plasma glucose (PG) increase to ≥3.9 mmol/L (≥70 mg/dL) or ≥1.1 mmol/L (≥20 mg/dL) increase from the PG nadir within 30 minutes of receiving glucagon]. Non‐inferiority was declared if the upper limit of the two‐sided 95% confidence interval (CI) of the mean difference in the percentage of patients achieving treatment success (IMG minus NG) was 2 patients were rhinalgia, increased blood pressure, nausea, ear pain and vomiting in the NG group, and nausea and vomiting in the IMG group. Conclusion Nasal glucagon was non‐inferior to IMG for successful treatment of insulin‐induced hypoglycaemia in Japanese patients with T1DM/T2DM, supporting use of NG as a rescue treatment for severe hypoglycaemia.