EN05 - Comparison of Transmucosal and Subcutaneous Glucagon for Treating Insulin-Induced Hypoglycemia in Healthy Cats

Abstract: Background – Severe hypoglycemia is a life-threatening complication of insulin therapy in cats, and rapid, practical rescue treatments are needed. Data on transmucosal glucagon for insulin-induced hypoglycemia (IIH) in cats is limited. Objectives – To compare intranasal (IN) and rectal transmucosal glucagon with subcutaneous (SQ) glucagon and IN placebo for reversal of induced IIH in healthy cats, and to assess safety and administration time. Animals – Six healthy adult research cats. Methods – In a randomized, non-blinded, placebo-controlled crossover study, hypoglycemia was induced using ultrashort-acting insulin followed by administration of either IN glucagon powder, rectal glucagon powder, SQ glucagon, or IN placebo. Blood glucose was measured at baseline, after hypoglycemia induction at a target 2.8mmol/L, and serially for 90 minutes post-treatment. Plasma glucagon and potassium concentrations were measured at baseline, after hypoglycemia induction, and 15- and 30-minutes post-administration. Time to prepare and administer each treatment was recorded. Results – Blood glucose increased significantly following glucagon administration by all routes (IN: 2.6–11.2 mmol/L, P = 0.006; rectal: 2.6–9.7 mmol/L, P = 0.002; SQ: 2.6–10.15 mmol/L), but not with placebo. Plasma glucagon peaked at 15 minutes, with the highest concentrations after IN administration (1562 pmol/L). Insulin administration lead to mild to moderate hypokalemia and partially corrected after all treatment. Mild adverse events were observed from glucagon administration. Conclusions and Clinical Importance – Transmucosal glucagon is effective and well tolerated for reversing IIH in cats. IN glucagon produces the most rapid and robust response, supporting its potential as a practical, non-invasive emergency therapy.