Six month administration of gelified intranasal insulin in 16 type 1 diabetic patients under multiple injections: Efficacy vs subcutaneous injectionsand local tolerance

Objective: Nasal insulin administration is a potential route for intensive insulin management, less invasive and more rapid than subcutaneous injectio ns. Previous studies have shown poor bioavailability (less than 15%) with n asal insulin administration with various absorption enhancers. The aim of t he study was to evaluate in type 1 diabetic patients, the metabolic efficac y and local tolerance of a new gelified sprayed nasal insulin containing gl ychocolate and methylcellulose as absorption promoters. Material and methods: The study was conducted in 16 type 1 diabetic patient s (HbA1c 8.6 +/- 0.2%) in a cross-over trial including 2 six month randomiz ed periods: a) NPH twice daily + 3 pre-prandial nasal insulin doses + nasal supplementation in case of unexpected hyperglycaemia; b) NPH twice daily 3 pre-prandial regular insulin injections. End points were HbA1c levels, hy poglycaemic episodes and tolerance evaluated at month 0, 2, 6 and 8 on clin ical symptoms and objective nasal assessments. Results: Four patients were withdrawn because of nasal burning (3 cases) an d persistent sinusitis ii case), and one patient had purulent sinusitis at the month 6 examination. At month 6, HbA1c levels were comparable (8.3 +/- 0.1 vs 8.6 +/- 0.1%, m +/- SEM; NS) for nasal and subcutaneous period respe ctively. The number of hypoglycaemic events was identical during the 2 peri ods (88 episodes). Nasal tolerance with the gelified form was better than w ith the already reported lyophilized form but, when present, symptoms were more marked, suggesting a potentiating additional role of methylcellulose e xcipient on nasal intolerance. Conclusions: II Gelified nasal insulin is as efficient as subcutaneous regu lar insulin in type I diabetic patients. 2) Other galenic forms should be i nvestigated to improve,nasal tolerance and bioavailability.