Effect of the fast-acting insulin analog lispro on the risk of nocturnal hypoglycemia during intensified insulin therapy

OBJECTIVE - To measure the effectiveness of insulin lispro, a East-acting i nsulin analog, in reducing hypoglycemic episodes when used in a basal bolus regimen by patients with type 1 diabetes using intensive insulin therapy. RESEARCH DESIGN AND METHODS - In 11 diabetes outpatient clinics in the U.K. , 165 subjects with type 1 diabetes were enrolled in a randomized crossover open-label study with a 2-month run-in period and then treated with a basa l bolus regimen. Patients used human NPH insulin at night with either preme al insulin lispro for 4 months followed by human regular insulin for anothe r 4 months or human regular insulin for 4 months followed by insulin lispro for another 4 months. The main outcome measures were the number of hypogly cemic episodes during both treatments and HbA(1c) level. RESULTS - A total of 135 patients were randomized, with 68 receiving insuli n lispro and 67 receiving human regular insulin for the first 4 months. The data for the first 4 months of treatment only were compared as two indepen dent groups because of a period effect and a treatment-period interaction, Glycemic control was equally tight during treatment with human regular insu lin (HbA(1c), 6.2 +/- 0.8%) and insulin lispro (6.0 +/- 0.9%). A total of 1 ,156 hypoglycemic episodes occurred during treatment with human regular ins ulin compared with 775 hypoglycemic episodes that occurred during treatment with insulin lispro (P = 0.04), This difference was chiefly because of a r educed number of nocturnal episodes (181 vs. 52, P = 0.001) in the insulin lispro group. CONCLUSIONS - The use of a fast-acting insulin analog, insulin lispro, as p art of a basal bolus regimen reduces nocturnal hypoglycemia in patients wit h type 1 diabetes who maintain tight glycemic control during intensive insu lin therapy.