Nasal glucagon was efficacious in reversing insulin-induced hypoglycaemia without increasing risk of secondary hyperglycaemia

Background and Aims Nasal glucagon (NG) contains 3-mg glucagon dry powder absorbed passively through nasal mucosa. We evaluated efficacy, pharmacodynamics, and safety of NG compared to injectable-glucagon (IG) in reversing insulin-induced hypoglycaemia in adults with T1D or T2D. Methods: Data from 2 randomised, cross-over studies was analysed. Treatment success was defined as increase in blood glucose to ≥3.9mmol/L or increase of ≥1.1mmol/L from nadir blood glucose within 15 minutes of receiving glucagon. Pharmacodynamic data, including area under the curve above 7.8mmol/L (∆7.8AUC [1-4hr]), evaluated risk of secondary hyperglycaemia. Tolerability was assessed with treatment-emergent adverse events and a nasal symptom questionnaire. Results: A similar proportion of NG (97.8% [131/134)] and IG patients (97.0% [130/134]) achieved treatment success, with mean time 11.7 and 10.4 minutes, (p< 0.001) respectively. Median time for both was 10 minutes. Geometric least square mean maximal blood glucose (BGmax) for NG and IG were 10.8 and 11.4 mmol/L (p < 0.001), respectively. NG had significantly lower ∆7.8AUC (1-4hr) (p< 0.001), with 42% reduction compared to IG. NG had similar rates of nausea (19.1%) and vomiting (8.5%) versus IG (28.8% and 11.5%, respectively), with higher rates of side effects related to nasal administration (headache [7.8% NG, 5.8% IG], upper respiratory tract irritation [6.4% NG, 0.7% IG]). Separate T1D and T2D analyses showed similar results as T1D and T2D groups combined. Conclusion: NG was efficacious and well tolerated in reversing insulin-induced hypoglycaemia in adults with T1D or T2D and did not increase the risk of secondary hyperglycaemia compared to IG.

Publication History

Article published online:
06 May 2021