Table 5.
Subgroup analyses of the effects of metformin.
| Subgroup title | No. of studies | No. of animals | Weighted mean difference | Heterogeneity | Subgroup difference | ||
|---|---|---|---|---|---|---|---|
| 95% CI | P-value | I 2 | P-value | ||||
| 1 Rat gender | 12 | 198 | |||||
| 1.1 BBB scale at 3rd day | 9 | 164 | P = 0.31 | ||||
| 1.1.1 Male | 3 | 50 | 0.70 [−0.04, 1.45] | 0.06 | 75 | 0.02 | |
| 1.1.2 Female | 6 | 114 | 0.24 [−0.26, 0.74] | 0.35 | 64 | 0.02 | |
| 1.2 BBB scale at 7th day | 12 | 198 | P = 0.14 | ||||
| 1.2.1 Male | 5 | 72 | 1.06 [0.39, 1.72] | 0.002 | 69 | 0.01 | |
| 1.2.2 Female | 7 | 126 | 1.63 [1.25, 2.01] | <0.00001 | 0 | 0.44 | |
| 1.3 BBB scale at 14th day | 11 | 186 | P = 0.57 | ||||
| 1.3.1 Male | 5 | 72 | 2.97 [1.12, 4.83] | 0.002 | 93 | <0.00001 | |
| 1.3.2 Female | 6 | 114 | 2.42 [1.99, 2.85] | <0.00001 | 0 | 0.44 | |
| 1.4 BBB scale at 21th day | 8 | 120 | P = 0.81 | ||||
| 1.4.1 Male | 5 | 72 | 3.96 [1.46, 6.47] | 0.002 | 95 | <0.00001 | |
| 1.4.2 Female | 3 | 48 | 3.64 [2.75, 4.54] | <0.00001 | 48 | 0.12 | |
| 1.5 BBB scale at 28th day | 9 | 136 | P = 0.75 | ||||
| 1.5.1 Male | 5 | 72 | 3.61 [1.02, 6.25] | 0.006 | 97 | <0.00001 | |
| 1.5.2 Female | 4 | 64 | 3.20 [2.58, 3.83] | <0.00001 | 0 | 0.68 | |
| 2 Injury model | 12 | 198 | |||||
| 2.1 BBB scale at 3rd day | 9 | 164 | P < 0.00001 | ||||
| 2.1.1 Compression | 5 | 114 | 0.01 [−0.23, 0.25] | 0.93 | 0 | 0.58 | |
| 2.1.2 Contusion | 4 | 50 | 1.21 [0.80, 1.62] | <0.00001 | 0 | 0.73 | |
| 2.2 BBB scale at 7th day | 12 | 198 | P = 0.29 | ||||
| 2.2.1 Compression | 7 | 136 | 1.26 [0.79, 1.72] | <0.00001 | 51 | <0.00001 | |
| 2.2.2 Contusion | 5 | 62 | 1.77 [0.96, 2.57] | <0.0001 | 59 | 0.05 | |
| 2.3 BBB scale at 14th day | 11 | 186 | P = 0.21 | ||||
| 2.3.1 Compression | 7 | 136 | 2.47 [1.50, 3.43] | <0.00001 | 81 | <0.00001 | |
| 2.3.2 Contusion | 4 | 50 | 3.28 [2.43, 4.13] | <0.00001 | 55 | 0.08 | |
| 2.4 BBB scale at 21th day | 8 | 120 | P = 0.33 | ||||
| 2.4.1 Compression | 4 | 70 | 3.33 [1.19, 5.47] | 0.002 | 93 | <0.00001 | |
| 2.4.2 Contusion | 4 | 50 | 4.61 [3.21, 6.01] | <0.00001 | 77 | 0.004 | |
| 2.5 BBB scale at 28th day | 9 | 136 | P = 0.61 | ||||
| 2.5.1 Compression | 5 | 86 | 3.21 [1.27, 5.15] | 0.001 | 91 | <0.00001 | |
| 2.5.2 Contusion | 4 | 50 | 3.89 [2.18, 5.61] | <0.00001 | 91 | <0.00001 | |
| 3 Administration timing | 12 | 192 | |||||
| 3.1 BBB scale at 3rd day | 9 | 158 | P < 0.0001 | ||||
| 3.1.1 Immediately | 6 | 124 | 0.04 [−0.19, 0.27] | 0.71 | 0 | 0.50 | |
| 3.1.2 ≥ 1 day | 3 | 34 | 1.05 [0.61, 1.50] | <0.00001 | 3 | 0.36 | |
| 3.2 BBB scale at 7th day | 12 | 192 | P = 0.03 | ||||
| 3.2.1 Immediately | 8 | 146 | 1.58 [1.26, 1.90] | <0.00001 | 0 | 0.56 | |
| 3.2.2 ≥ 1 day | 4 | 46 | 0.68 [−0.07, 1.42] | 0.07 | 57 | 0.07 | |
| 3.3 BBB scale at 14th da | 11 | 180 | P = 0.54 | ||||
| 3.3.1 Immediately | 8 | 134 | 2.77 [2.15, 3.39] | <0.00001 | 49 | 0.05 | |
| 3.3.2 ≥ 1 day | 4 | 46 | 2.06 [−0.16, 4.28] | 0.07 | 95 | <0.00001 | |
| 3.4 BBB scale at 21th day | 8 | 114 | P = 0.47 | ||||
| 3.4.1 Immediately | 4 | 68 | 4.31 [3.21, 5.49] | <0.00001 | 67 | 0.02 | |
| 3.4.2 ≥ 1 day | 4 | 46 | 3.13 [0.14, 6.12] | 0.04 | 97 | <0.00001 | |
| 3.5 BBB scale at 28th day | 9 | 130 | P = 0.59 | ||||
| 3.5.1 Immediately | 5 | 84 | 3.68 [2.91, 4.44] | <0.00001 | 39 | 0.14 | |
| 3.5.2 ≥ 1 day | 4 | 46 | 2.74 [−0.59, 6.07] | 0.11 | 98 | <0.00001 | |
| 4 Number of injections | 12 | 198 | |||||
| 4.1 BBB scale at 3rd day | 9 | 164 | P = 0.44 | ||||
| 4.1.1 Repeated injection | 8 | 136 | 0.47 [−0.05, 0.98] | 0.07 | 75 | 0.0002 | |
| 4.1.2 Single injection | 1 | 28 | 0.19 [−0.28, 0.67] | 0.42 | |||
| 4.2 BBB scale at 7th day | 12 | 198 | P = 0.83 | ||||
| 4.2.1 Repeated injection | 10 | 160 | 1.41 [0.94, 1.88] | <0.00001 | 56 | 0.006 | |
| 4.2.2 Single injection | 2 | 38 | 1.49 [0.93, 2.05] | <0.00001 | 0 | 0.73 | |
| 4.3 BBB scale at 14th day | 11 | 186 | P = 0.009 | ||||
| 4.3.1 Repeated injection | 9 | 148 | 2.44 [1.60, 3.28] | <0.00001 | 84 | <0.00001 | |
| 4.3.2 Single injection | 2 | 38 | 4.27 [3.18, 5.36] | <0.00001 | 0 | 0.84 | |
| 4.4 BBB scale at 21th day | 8 | 120 | P = 0.09 | ||||
| 4.4.1 Repeated injection | 6 | 82 | 3.58 [1.96, 5.20] | <0.0001 | 93 | <0.00001 | |
| 4.4.2 Single injection | 2 | 38 | 5.41 [4.03, 6.80] | <0.00001 | 23 | 0.25 | |
| 4.5 BBB scale at 28th day | 9 | 136 | P = 0.05 | ||||
| 4.5.1 Repeated injection | 7 | 98 | 3.11 [1.44, 4.79] | 0.0003 | 95 | <0.00001 | |
| 4.5.2 Single injection | 2 | 38 | 5.21 [3.93, 6.50] | <0.00001 | 0 | 0.84 | |
| 5 Administration dose | 12 | 198 | |||||
| 5.1 BBB scale at 3rd day | 9 | 164 | P = 0.28 | ||||
| 5.1.1 ≤ 50 mg/kg | 7 | 126 | 0.25 [−0.20, 0.70] | 0.27 | 70 | 0.001 | |
| 5.1.2 > 50 mg/kg | 3 | 38 | 0.75 [−0.04, 1.54] | 0.06 | 57 | 0.10 | |
| 5.2 BBB scale at 7th day | 12 | 198 | P = 0.34 | ||||
| 5.2.1 ≤ 50 mg/kg | 9 | 148 | 1.49 [1.17, 1.81] | <0.00001 | 10 | 0.001 | |
| 5.2.2 > 50 mg/kg | 4 | 50 | 0.98 [−0.03, 1.99] | 0.06 | 66 | 0.03 | |
| 5.3 BBB scale at 14th day | 11 | 186 | P = 0.42 | ||||
| 5.3.1 ≤ 50 mg/kg | 8 | 136 | 3.00 [2.31, 3.69] | <0.00001 | 67 | 0.0007 | |
| 5.3.2 > 50 mg/kg | 4 | 50 | 2.15 [0.19, 4.11] | 0.03 | 86 | <0.0001 | |
| 5.4 BBB scale at 21th day | 8 | 120 | P = 0.11 | ||||
| 5.4.1 ≤ 50 mg/kg | 5 | 70 | 4.69 [3.66, 5.72] | <0.00001 | 73 | 0.001 | |
| 5.4.2 > 50 mg/kg | 4 | 50 | 2.60 [0.22, 4.98] | 0.03 | 88 | <0.0001 | |
| 5.5 BBB scale at 28th day | 9 | 136 | P = 0.04 | ||||
| 5.5.1 ≤ 50 mg/kg | 6 | 86 | 4.32 [3.32, 5.33] | <0.00001 | 72 | 0.0007 | |
| 5.5.2 > 50 mg/kg | 4 | 50 | 2.01 [0.02, 4.01] | 0.05 | 89 | <0.00001 | |