Comparing the efficacy of transmucosal and subcutaneous glucagon administration in response to insulin-induced hypoglycemia in healthy cats.

ObjectivesThe aim of the present study was to evaluate the efficacy of two different formulations of glucagon given by three different routes (subcutaneous [SC], rectal [RCT] and intranasal [IN]) for correcting insulin-induced hypoglycemia in cats and to describe any adverse effects and compare the time required for administration by each route.MethodsA randomized, non-blinded, sham-controlled crossover study was conducted in six healthy cats, with a 7-day washout period between treatments. Hypoglycemia was induced using a constant rate infusion (CRI) of rapid-acting insulin lispro. Glucagon nasal powder (single-dose, ready-to-use) was given intranasally and rectally and compared with SC glucagon injection and IN sham control. Blood glucose (BG) concentration was measured from samples collected at baseline (T-15), after induction of hypoglycemia (T0) and at 5-min intervals for 30 mins, and then at 15-min intervals for 1 h after glucagon administration. Plasma glucagon and potassium (K+) concentrations were measured at T-15, T0, T15 and T30 after glucagon administration. The time taken to prepare and administer each treatment was recorded.ResultsMedian BG was 2.6 mmol/l at T0 and increased significantly after glucagon administration by all routes, reaching peak median concentrations of 11.2 mmol/l (IN), 9.7 mmol/l (RCT) and 10.15 mmol/l (SC). Plasma glucagon concentrations increased markedly by T15, with the highest concentrations observed after IN administration (1562 pmol/l), followed by SC (191.7 pmol/l) and RCT (158.5 pmol/l) routes of administration. Plasma K+ decreased after insulin administration and increased modestly by T30 after glucagon administration by all routes. No serious adverse effects occurred after glucagon administration.Conclusions and relevanceTransmucosal glucagon effectively restores BG towards baseline after insulin-induced hypoglycemia with minimal side effects. The IN route resulted in the highest plasma glucagon and BG concentrations compared with the RCT and SC routes of administration. Further studies are needed to quantify the efficacy and safety of transmucosal glucagon in diabetic cats in response to spontaneous insulin-induced hypoglycemia.