Serum insulin aspart concentrations following high-dose insulin aspart administered directly into the duodenum of healthy subjects: an open-labeled, single-blinded, and uncontrolled exploratory trial

Abstract

Objective: The goal of this study was to determine the bioavailability of high-dose insulin aspart administered directly into the duodenum of healthy subjects.

Methods: In a pilot study, four subjects each received four escalating doses of a 1-ml solution of insulin aspart (100, 300, 600, and 1000 IU, respectively) directly into the duodenum. In the following main study, eight subjects each received two identical doses of insulin aspart of 1000 IU, in 4- and 8-ml solutions, respectively, directly into the duodenum. Subjects in the main study also received an intravenous and a subcutaneous injection of 4 to 6 IU of insulin aspart.

Results: A considerable number of samples and, in some cases, consecutive samples revealed significantly increased concentrations of serum insulin aspart. Despite the significant serum insulin aspart concentrations, no significant changes of plasma glucose were measured. Moreover, no significant suppression of endogenous insulin secretion was detected, as assessed by the levels of serum human insulin.

Conclusions: Administration of high-dose insulin aspart directly into the duodenum of healthy subjects resulted in significantly increased serum insulin aspart concentrations in a high number of consecutive samples using a specific enzyme-linked immunosorbent assay. However, no significant changes in the levels of plasma glucose or serum human insulin were observed. Thus, the study did not provide any evidence of biological activity of the original insulin aspart molecule after high-dose administration directly into the duodenum.

Figure 1.

Duodenal insulin administration. Individual serum insulin aspart (S-IAsp) levels for subjects (01, 02, 04, and 05) in the pilot study. (A) 100 IU IAsp, (B) 300 IU IAsp, (C) 600 IU IAsp, and (D) 1000 IU IAsp.

Figure 2.

Duodenal insulin administration. Mean serum insulin aspart (S-IAsp) concentrations + positive SD. (A) Pilot study and (B) main study. Please observe different scale on Y-axes.

Figure 3.

Duodenal insulin administration. Mean plasma glucose (PG) concentrations + SD. (A) Pilot study and (B) main study.

Figure 4.

Duodenal insulin administration. Mean intravenous glucose infusion (glu.inf.) g/H + positive SD. (A) Pilot study and (B) main study.

Figure 5.

Duodenal insulin administration. Mean serum human insulin (S-HI) concentrations + SD. (A) Pilot study and (B) main study.

Figure 6.

Duodenal insulin administration. pH measurement from subject 01 from the pilot study. pH 1 and pH 2 refer to the two pH channels on the pH meter in the duodenum.

Figure 7.

Duodenal insulin administration. Individual serum insulin aspart (S-IAsp) levels for subjects (05 to 13) in the main study. (A) 1000 IU IAsp, 4 ml, and (B) 1000 IU IAsp, 8 ml. Please observe different scale on Y axes.

Figure 8.

Mean serum insulin aspart (S-IAsp) concentrations + positive SD. (A) Intravenous (I.V.) insulin aspart administration, 4/6 IU. (B) Subcutaneous (S.C.) insulin aspart administration. Please observe different scale on Y axes.