The Effect of Mixing Regular- and Intermediate-Acting Insulins on Their Absorption and Biological Activity¹)

Abstract

Many insulin-dependent diabetics are now treated with different regimens of short- and intermediate-acting insulins. The new L-insulin S.N.C. (Berlin-Chemie) is thought to be appropriate for a combination with regular insulin. We investigated whether or not absorption kinetics and biological activity changes when L-insulin S.N.C. is mixed with regular insulin S.N.C. Eight non-obese healthy male subjects were connected to the BIOSTATOR. After an overnight fast 0.1 U of insulin S.N.C. and 0.3 U per kg b.w. of L-insulin S.N.C. or Monotard MC insulin (NOVO) were administered either in a mixture or separately. Injecting L-insulin S.N.C. and insulin S.N.C. in a mixture there was some, but not a statistically significant, delay in absorption of insulin. A mixture of insulin S.N.C. and Monotard provoked a marked delay of absorption during the first two hours. To examine biological activity we used the BIOSTATOR (glucose controlled dextrose infusion system). Glucose infusion rate necessary to keep blood glucose steady state concentration was taken as a measure of insulin action. Whereas mixing of insulin S.N.C. and L-insulin S.N.C. only slightly changed the profile of biological activity, a mixture of insulin S.N.C. and Monotard has a clear-cut higher potency during the late phase when compared with separately injected insulins. Therefore, insulin S.N.C. and Monotard should not be mixed. A mixture of insulin S.N.C. and L-insulin S.N.C. is also not recommended but can be done in exceptional cases.