Table 2

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 IGlar87 (165)1,720 (42)0.90 (0.86, 0.94)
  US IGlar89 (167)1,900 (35)
  LY IGlar79 (156)1,810 (40)0.91 (0.87, 0.96)
  EU IGlar80 (157)1,980 (36)
  EU IGlar40 (75)2,000 (35)0.98 (0.91, 1.05)
  US IGlar40 (76)2,060 (39)
 Cmax (pmol/L)
  LY IGlar88 (167)103 (41)0.92 (0.87, 0.96)
  US IGlar89 (169)111 (34)
  LY IGlar80 (158)112 (39)0.95 (0.90, 1.00)
  EU IGlar80 (158)119 (34)
  EU IGlar40 (76)120 (33)0.99 (0.92, 1.06)
  US IGlar40 (77)122 (37)
 tmax (h)§
  LY IGlar8812.000.50 (−0.76, 1.25)
  US IGlar8912.00
  LY IGlar8012.000.00 (−0.75, 0.75)
  EU IGlar8013.50
  EU IGlar4012.00−0.75 (−1.50, 0.50)
  US IGlar4012.00
Statistical analysis of pharmacodynamic parameters
 Gtot (mg/kg)
  LY IGlar88 (171)1,670 (60)0.91 (0.85, 0.98)
  US IGlar88 (170)1,820 (74)
  LY IGlar80 (158)2,580 (45)0.95 (0.91, 1.00)
  EU IGlar80 (158)2,710 (40)
  EU IGlar40 (76)1,870 (84)1.00 (0.89, 1.13)
  US IGlar40 (77)1,880 (77)
 Rmax (mg/kg/min)
  LY IGlar88 (171)2.12 (54)0.93 (0.88, 0.98)
  US IGlar88 (170)2.27 (58)
  LY IGlar80 (158)2.85 (46)0.99 (0.94, 1.04)
  EU IGlar80 (158)2.88 (41)
  EU IGlar40 (76)2.35 (67)0.97 (0.88, 1.07)
  US IGlar40 (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.