Glycemic Stability of Insulin Aspart Versus Insulin Lispro in Insulin Pump Therapy

Insulin instability in pump infusion systems can result in unexplained hyperglycemia in
patients on continuous subcutaneous insulin infusion (CSII) therapy. We have noted that
some pump patients develop glycemic instability with use of insulin lispro, and that this
resolves with change to insulin aspart. Several patients using lispro have reported noting
a whitish precipitate in the infusion set, and in two cases we have examined the catheters
and confirmed biochemically that this precipitate was insulin. Furthermore, in vitro
studies indicate that insulin aspart is more resistant to isoelectric precipitation than
insulin lispro. Although it has been rare for patients to notice a visible precipitate in
the pump catheter, there is a subset of patients using lispro who have noted that their
blood glucose levels will tend to rise 2 or more days after the insertion of a new pump
infusion system. These findings mirror bench studies showing that the relative stability
differences between aspart and lispro in pump infusion systems becomes more apparent over
time.

The endpoints examined in previous randomized clinical trials comparing aspart and lispro
were not directed specifically at assessing the effect of insulin type on glycemic
stability. In these previous studies, pump infusion systems were changed every 48 hours
whereas most pump patients routinely replace their infusion catheters only every 72-96
hours; this discrepancy may account for the failure of these trials to demonstrate the
difference in the stability of insulin aspart and lispro that has been noted in clinical
practice.

This investigator-initiated clinical trial is intended to assess the safety and efficacy of
CSII with insulin aspart compared to insulin lispro with use of pump infusion catheters for
up to 96 hours.

Inclusion Criteria:

- Type 1 diabetes treated with CSII at least 3 months.

- Males and females, > 18 years but < 75 years old.

- Hemoglobin A1c ≤ 8.0 % at measurement taken at week 0 (screening visit).

- Duration of diabetes ≥ 12 months.

- Willingness to perform self-blood glucose monitoring several times/day.

Exclusion Criteria:

- Previous insulin precipitation in pump infusion catheters.

- Daily insulin requirements > 25% of pump reservoir capacity. (This would preclude the
subject from using the pump infusion system for more than 3 days).

- Use of an insulin pump that does not have a downloadable record of basal and bolus
doses.

- Known or suspected allergy to trial products.

- Pregnancy, breast-feeding, intention to become pregnant or inadequate contraception
measures.

- Known or suspected alcohol or drug abuse.

- Impaired renal function with creatinine ≥ 1.7 mg/dl.

- Pronounced catheter site scarring.

- Chronic use of drugs that may influence glycemic control (e.g. steroids).

- Any other significant concomitant disease that would interfere with participation in
and completion of the trial.