Subcutaneous injection versus subcutaneous infusion of insulin: are the rates of absorption truly the same?

The question is, is insulin absorption after subcutaneous (SC) injection of a prandial insulin/insulin analog prior to a meal comparable to that of infusion of the same insulin dose as a bolus via an insulin pump? You might say, this is easy; let us check what published studies tell us about this topic. A search in PubMed using search terms, “injection infusion insulin subcutaneous pharmacokinetic” resulted in 69 hits on August 26, 2011. However, according to their titles, only two publications from 1983 studied this question.1,2 In one study, a pharmacokinetic (PK) model was used to describe the plasma concentration time profile after SC administration of insulin in patients with type 1 or type 2 diabetes.1 Continuous SC insulin infusion for 1 h at a rate of 3 ml/h (2–3 U/ml) resulted in comparable PK parameters to those generated by SC injection of insulin (40 U/ml). The authors concluded from their study that the absorption kinetics of insulin did not differ significantly between two modes of SC insulin administration in the patients studied. In the other study, six human insulin or porcine insulin preparations of either porcine were investigated after intravenous or SC infusion at two different rates (study I) and three preparations were investigated after SC bolus injection (study II) in healthy men, but SC injection or infusion were not studied in a head-to-head manner.2 For us, these studies, which are performed with outdated techniques and inappropriate study designs, are not conclusive. Are there reasons to believe that there might be clinically relevant differences in insulin absorption between SC injection and infusion? Let us review the relevant factors.