A Comparison of Human Ultralente‐and Lente‐based Twice‐daily Injection Regimens

Abstract

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.

Split-Mixed Insulin Regimen With Human Ultralente Before Supper and NPH (Isophane) Before Breakfast in Children and Adolescents With IDDM

“…Francis et al (34) compared pork lente to human ultralente insulin in subjects with raised fasting blood glucose concentrations and found that the latter was associated with significantly lower mean blood glucose concentrations before and after breakfast. Tunbridge et al (35) compared a twice-daily human ultralente regimen with a lente-based injection regimen in adults with IDDM and found that ultralente improved fasting blood glucose concentrations but offered no clinical advantage over lente insulin in subjects with more marked fasting hyperglycemia. Tunbridge et al (35) compared a twice-daily human ultralente regimen with a lente-based injection regimen in adults with IDDM and found that ultralente improved fasting blood glucose concentrations but offered no clinical advantage over lente insulin in subjects with more marked fasting hyperglycemia.…”

Clinical Pharmacology of Human Insulin

“…Clinical trials showed that such an insulin regimen resulted in lower fasting blood glucose concentrations than twice-daily injections of human lente insulin (79,80). If only once-daily injection of human ultralente was used, injection in the morning resulted in a higher fasting blood glucose concentration than injection at bedtime (81,82).…”

The use of human ultralente is limited by great intraindividual variability in overnight plasma insulin profiles

“…On the other hand, Parillo et al [16] found lower fasting blood glucose with ultralente insulin than with NPH insulin, but in that study the NPH insulin was administered before dinner, which increases the risk that the duration is too short for controlling fasting blood glucose. Ultralente insulin mixed with regular insulin in the same syringe could improve the fasting blood glucose in some patients compared to lente insulin in a two-dose regimen, but it also more commonly caused serious hypoglycaemic events during the early morning hours [15]. A high variation of intra-individual insulin absorption has also been found with other longer-acting insulin preparations, such as NPH and lente insulin [17].…”