Intranasal insulin administration is a novel approach to slow the progression of diabetic polyneuropathy (DPN). We performed a pilot randomized controlled trial of intranasal insulin in 12 type 1 diabetes mellitus patients with DPN to assess safety. We administered intranasal insulin for 6 weeks using biweekly dose-escalation up to 160 IU/d or intranasal saline. The primary outcome measure was frequency of hypoglycaemia. Frequency of mild (mHG) and
serious hypoglycaemic (sHG) events was recorded. Secondary outcomes included clinical (Utah Early Neuropathy Score (UENS)) and laboratory (corneal confocal microscopy and
electrophysiology) measures. There were no differences in glycemia between groups after supervised initial administration. The 40 IU/d and 80 IU/d doses were safe and well tolerated with comparable mHG events between groups. One intranasal insulin subject suffered a sHG at home while receiving 160 IU/d. Intranasal insulin was safe and well tolerated at 40 and 80 IU/d.