Hypoglycaemia with insulin aspart: a double‐blind, randomised, crossover trial in subjects with Type 1 diabetes

Abstract

Aims To compare the effects of the rapid‐acting insulin analogue insulin aspart and soluble human insulin on hypoglycaemia and glycaemic control in patients with Type 1 diabetes when injected immediately before meals as part of intensive insulin therapy. Methods In this multinational, double‐blind, randomised, crossover trial, 155 patients with Type 1 diabetes (HbA_1c < 8.0%) were symmetrically randomised to two 16‐week treatment periods on either type of insulin, both injected 0–5 min before meals. NPH insulin was given as basal insulin once or twice daily as needed, and insulin dosages were regularly adjusted using pre‐defined algorithms to maintain tight glycaemic control. Treatment periods were separated by a 4‐week washout. Results The rate of major nocturnal (24.00–06.00 h) hypoglycaemic episodes was 72% lower with insulin aspart than with human insulin (0.067 vs. 0.225 events/month; P = 0.001). Total rate of major hypoglycaemia did not differ significantly between treatments (insulin aspart/human insulin relative risk 0.72; 95% CI 0.47–1.09, P = 0.12). The rate of minor events was significantly reduced by 7% with insulin aspart (P = 0.048). Reductions in rate of hypoglycaemia were achieved with maintained overall glycaemic control: Mean HbA_1c remained constant, slightly below 7.7% on both treatments. Conclusions The use of insulin aspart in an intensive insulin regimen in patients with tightly controlled Type 1 diabetes led to clinically significant reductions in major nocturnal hypoglycaemia with no deterioration in glycaemic control. Major nocturnal hypoglycaemia appears to be a strong clinical indication for the use of rapid‐acting insulin analogues during intensive insulin therapy.