Comparison of the primary pharmacokinetic and pharmacodynamic parameters of LY IGlar, EU-approved IGlar, and US-approved IGlar in three 2-treatment, four-period, crossover design studies
| Treatment (0.5 units/kg) | N (n) | Geometric mean (CV%)* | Ratio of LS geometric means (test†/reference) (90% CI)‡ |
|---|---|---|---|
| Statistical analysis of pharmacokinetic parameters | |||
| AUC[0–24] (pmol ⋅ h/L) | |||
| LY IGlar† | 87 (165) | 1,720 (42) | 0.90 (0.86, 0.94) |
| US IGlar | 89 (167) | 1,900 (35) | |
| LY IGlar† | 79 (156) | 1,810 (40) | 0.91 (0.87, 0.96) |
| EU IGlar | 80 (157) | 1,980 (36) | |
| EU IGlar† | 40 (75) | 2,000 (35) | 0.98 (0.91, 1.05) |
| US IGlar | 40 (76) | 2,060 (39) | |
| Cmax (pmol/L) | |||
| LY IGlar† | 88 (167) | 103 (41) | 0.92 (0.87, 0.96) |
| US IGlar | 89 (169) | 111 (34) | |
| LY IGlar† | 80 (158) | 112 (39) | 0.95 (0.90, 1.00) |
| EU IGlar | 80 (158) | 119 (34) | |
| EU IGlar† | 40 (76) | 120 (33) | 0.99 (0.92, 1.06) |
| US IGlar | 40 (77) | 122 (37) | |
| tmax (h)§ | |||
| LY IGlar† | 88 | 12.00 | 0.50 (−0.76, 1.25) |
| US IGlar | 89 | 12.00 | |
| LY IGlar† | 80 | 12.00 | 0.00 (−0.75, 0.75) |
| EU IGlar | 80 | 13.50 | |
| EU IGlar† | 40 | 12.00 | −0.75 (−1.50, 0.50) |
| US IGlar | 40 | 12.00 | |
| Statistical analysis of pharmacodynamic parameters | |||
| Gtot (mg/kg) | |||
| LY IGlar† | 88 (171) | 1,670 (60) | 0.91 (0.85, 0.98) |
| US IGlar | 88 (170) | 1,820 (74) | |
| LY IGlar† | 80 (158) | 2,580 (45) | 0.95 (0.91, 1.00) |
| EU IGlar | 80 (158) | 2,710 (40) | |
| EU IGlar† | 40 (76) | 1,870 (84) | 1.00 (0.89, 1.13) |
| US IGlar | 40 (77) | 1,880 (77) | |
| Rmax (mg/kg/min) | |||
| LY IGlar† | 88 (171) | 2.12 (54) | 0.93 (0.88, 0.98) |
| US IGlar | 88 (170) | 2.27 (58) | |
| LY IGlar† | 80 (158) | 2.85 (46) | 0.99 (0.94, 1.04) |
| EU IGlar | 80 (158) | 2.88 (41) | |
| EU IGlar† | 40 (76) | 2.35 (67) | 0.97 (0.88, 1.07) |
| US IGlar | 40 (77) | 2.44 (63) |
n, number of observations; N = number of subjects.
↵*Summary statistics of pharmacokinetic and pharmacodynamic parameters; does not reflect results of the statistical analysis.
↵†The test treatment in each comparison.
↵‡Statistical model: log(parameter) = period + sequence + treatment + error, subject (random), period sequence treatment (categorical).
↵§Median or median difference (95% CI) are presented for tmax. tmax was analyzed using a nonparametric approach based on the Hodges-Lehmann method. Analysis was based on subject's tmax values averaged across the 2 occasions where the same treatment was administered, if applicable.