Additional Lunchtime Basal Insulin During Insulin Lispro Intensive Therapy in a Randomized, Multicenter, Crossover Study in Adults

Abstract

OBJECTIVE—This study was performed to evaluate whether an additional dose of NPH insulin at lunchtime might overcome the deleterious effects of waning basal insulinemia on pre-dinner and evening glucose values during insulin lispro intensive therapy with once daily basal insulin at night.

RESEARCH DESIGN AND METHODS—The study was a 10-month multicenter, randomized, crossover trial. After a 2-month run-in period, subjects injected NPH insulin once (1 × NPH) or twice (2 × NPH) daily for 4 months in a randomized order. Adult patients were included if they had HbA_1c levels <8.5%. Efficacy measures were HbA_1c levels, 8-point glucose profiles, and the frequency of hypoglycemia. The statistical analysis included a within-patient comparison for crossover trials.

RESULTS—In all, 104 patients completed the trial. The mean HbA_1c level before randomization was 7.1 ± 0.85%. The HbA_1c levels did not change significantly within patients (t test, mean difference = 0.06%; 95% confidence interval [CI] −0.073 to 0.20). The pre-dinner blood glucose values were significantly lower during the 2 × NPH daily protocol, with a mean difference of 0.76 mmol/l (t test, P = 0.004; CI 0.25 to 1.3). In the evening, the frequency of hypoglycemia increased significantly during the 2 × NPH daily protocol with a median difference of 0.56 mild episodes/30 days (P = 0.001) and 6.9 severe episodes/patient year (P = 0.007), respectively.

CONCLUSIONS—Equal HbA_1c levels and increasing frequencies of hypoglycemia in the evening overshadow the slight improvement of the evening glucose profiles during a regimen with 2 × NPH daily insulin. Therefore, generalized use of a second injection of NPH insulin at lunchtime cannot be recommended to all adult patients with type 1 diabetes using intensive insulin lispro therapy.