The subcutaneous absorption and resulting changes in plasma insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations after subcutaneous bolus injection of three soluble human insulin analogues (AspB9GluB27, monomeric; AspB28, mixture of monomers and dimers; and AspB10, dimeric) and soluble human insulin were evaluated.

Research Design and Methods

Fasting healthy male volunteers (n = 7) were studied on five occasions 1 wk apart randomly receiving 0.6 nmol·kg−1 s.c. 125I-labeled AspB10 or soluble human insulin (Novolin R, Novo, Copenhagen); 1st study and 0.6 nmol·kg−1 s.c. 125I-labeled AspB28, AspB9GluB27 or soluble human insulin (2nd study). Residual radioactivity at the injection site was measured over 8 h with frequent venous sampling for plasma immunoreactive insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations.


The three analogues were absorbed 2–3 times faster than human insulin. The mean ± SE time to 50% residual radioactivity was 94 ± 6 min for AspB10 compared with 184 ± 10 min for human insulin (P < 0.001), 83 ± 8 min for AspB28 (P < 0.005), and 63 ± 9 min for AspB9GluB27 (P < 0.001) compared with 182 ± 21 min for human insulin. delta Peak plasma insulin analogue levels were significantly higher after each analogue than after human insulin (P < 0.005). With all three analogues, the mean hypoglycemic nadir occurred earlier at 61–65 min postinjection compared with 201–210 min for the reference human insulins (P < 0.005). The magnitude of the hypoglycemic nadir was greater after AspB9GluB27 (P < 0.05) and AspB28 (P < 0.001) compared with human insulin. There was a significantly faster onset and offset of responses in C-peptide and intermediary metabolite levels after the analogues than after human insulin (P < 0.05).


The rapid absorption and biological actions of these analogues offer potential therapeutic advantages over the current short-acting neutral soluble insulins.

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