A comparison of human ultralente- and lente-based twice-daily injection regimens

The problem of fasting hyperglycaemia remains unresolved on currently used twice-daily injection regimens. Human ultralente insulin is of longer duration than human lente and differs from it only in the nature of the zinc-insulin complex. In a 6-month double-blind crossover study these insulins were compared in 66 patients who were randomized to human ultralente or human lente insulin given together with human soluble insulin in a twice-daily injection regimen. Patients were seen monthly and crossed over after 3 months treatment. Fasting blood glucose concentrations on the ultralente regimen were considerably lower than on the lente regimen, the difference being statistically significant (6.6 +/- 0.5 vs 8.2 +/- 0.5 mmol l-1, p less than 0.05), but only present in those patients with fasting concentrations below the median. Glycosylated haemoglobin was identical on both regimens (9.3 +/- 0.2%). The evening ultralente dose was slightly but significantly lower than the evening lente dose (14.9 +/- 0.8 vs 15.5 +/- 0.8 U, p less than 0.05) thus endorsing the lowering effect of ultralente on the fasting blood glucose concentration. However, the incidence of serious hypoglycaemic events was higher on the ultralente regimen (0.38 +/- 0.10 vs 0.09 +/- 0.04 events per patient-month, p less than 0.02), the majority of nocturnal events occurring between 0500 h and breakfast. We conclude that ultralente insulin can give an improved fasting blood glucose concentration but that in those patients with more marked fasting hyperglycaemia or with a nocturnal hypoglycaemia problem it offers no clinical advantage over human lente insulin in a twice-daily injection regimen.