PK/PD parameters
| Study | |||||
|---|---|---|---|---|---|
| Parameter | R+ | R- horizontal | R- up | R- down | P value |
| PK | |||||
| FIRI_AUC(0–end of study) (μU/mL · h−1) (*P < 0.05 vs. R+, R- horizontal, R- up; §P < 0.05 vs. R+) | 248 ± 88 | 206 ± 41§ | 188 ± 35§ | 323 ± 52* | 0.001 |
| FIRI Cmax (μU/mL) (*Cmax P < 0.05 vs. R- horizontal, R- up) | 24 ± 9.3* | 19 ± 3.5 | 17 ± 2.9 | 27 ± 3.1* | 0.001 |
| FIRI Tmax (h) | 4.7 ± 0.6 | 3.6 ± 2.2 | 4.6 ± 1.6 | 4.7 ± 0.6 | 0.143 |
| PD | |||||
| AUC plasma glucose (mg/dL · h−1) (*P < 0.05 vs. R- up) | 171 ± 61 | 205 ± 55 | 208 ± 53 | 164 ± 44* | 0.049 |
| Plasma glucose Tmax (h) (*P < 0.05 vs. R+, R- horizontal, R- up; §P < 0.05 vs. R+) | 17.3 ± 2.6 | 16.5 ± 1.8 | 15.4 ± 2.2§ | 19.7 ± 2.2* | 0.001 |
| Onset of action† (h) (*P < 0.05 vs. R+) | 2.2 ± 1.2 | 1.7 ± 1.2 | 1.7 ± 1 | 1 ± 0* | 0.008 |
| End of action† (h) (*P < 0.05 vs. R+, R- horizontal, R- up) | 13.9 ± 2.3 | 11.9 ± 2.1 | 11.1 ± 2.1 | 16.4 ± 2.3* | 0.001 |
| Duration of action† (h) (*P < 0.05 vs. R+, R- horizontal, R- up; §P < 0.05 vs. R+) | 11.8 ± 2.6 | 10.1 ± 1.8 | 9.4 ± 1.7§ | 15.4 ± 2.3* | 0.001 |
| GIR | |||||
| Cmax (mg/kg/min) (*P < 0.05 vs. R- horizontal, R- up; §P < 0.05 vs. R+) | 3.8 ± 2.8 | 2.6 ± 1.7 | 1.7 ± 1.2§ | 5.1 ± 3.0* | 0.001 |
| Tmax (h) | 6.2 ± 1.4 | 6.3 ± 1.2 | 5.4 ± 0.9 | 5.1 ± 0.7 | 0.206 |
| AUC0–end of study (mg/kg) (*P < 0.05 vs. R+, R- horizontal, R- up; §P < 0.05 vs. R+) | 1,342 ± 1,129 | 774 ± 637 | 481 ± 322§ | 1,957 ± 1,253* | 0.001 |
Data are mean ± SD. Boldface indicates significance at P < 0.05.
↵†See research design and methods for definition.