New Insulins

Saturday June 11, 2005
ADA Symposium
Supported by an unrestricted educational grant from Novo Nordisk Inc.

Chair
Robert Ratner, MD

Report by Joelle Escoffery, PhD

New advances in insulin therapy (ie, basal insulin analogs, rapid-acting insulin analogs, inhaled insulin, and premixed insulins), were discussed in this symposium.

In terms of basal insulin, NPH insulin was the standard for over 50 years, in spite of its high degree of variability. Newer basal insulin analogs, lantus and detemir, have improved upon NPH by showing decreased variability. Compared with NPH, these new basal insulin analogs also have demonstrated significant improvements in fasting plasma glucose and decreases in hypoglycemia (particularly nocturnal hypoglycemia). Detemir is also associated with less weight gain compared with NPH.

A variety of rapid-acting insulins also have become available in the last several years. In terms of time action profiles, the existing rapid-acting insulin analogs are remarkably similar, showing only minor differences in time course. Further, these differences are not associated with meaningful clinical changes.

One novel method of insulin delivery is inhaled insulin. A variety of devices that deliver both dry powder and liquid formulation insulin are currently in development. The efficacy of delivery varies with the device used, and the variability of inhaled insulin ranges from 15% to 30%, a rate that is comparable to subcutaneous insulin delivery. In terms of time action profiles, the different formulations are relatively similar on the whole, with an onset than is more rapid than regular insulin, but has a longer duration than insulin lispro. In efficacy studies, exubera has been shown to be comparable to subcutaneous insulin, with no loss of glycemic control among people with type 1 diabetes. The same results were demonstrated in a type 2 population, with the added benefit of less weight gain than is seen with subcutaneous insulin. In terms of safety, not short-term changes in pulmonary function were observed, but studies of longer duration are needed to confirm that finding.

Although physiologic insulin replacement with a basal and bolus regimen is preferable for achieving tight glycemic control, patient adherence is a major factor. One method for improving patient adherence is to use premixed insulins. A variety of studies have demonstrated that premixed insulin provides better glycemic control in type 2 diabetes, as compared with basal insulin. In the INITIATE study, patients inadequately controlled with oral medications were randomly assigned to oral medications plus insulin glargine or oral medications plus premixed insulin twice daily. Results demonstrated that patients receiving the premixed insulin (particularly patients with higher baseline A1C levels) had a bigger reduction in A1C than patients receiving insulin glargine. The results of this study support the efficacy of premixed insulin for the treatment of type 2 diabetes.