APPENDIX TABLE 9.
TWO-YEAR EXPLORATORY DATA
| Group 1 | MK-677 Yr 1 MK-677 Yr 2 |
Group 2 | MK-677 Yr 1 Placebo Yr 2 |
Group 3 | Placebo Yr 1 MK-677 Yr 2 |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean (SD) | Mean Change * |
95% CI | P vs. Baseline † | Mean (SD) | Mean Change * |
95% CI | P vs. Baseline † | Mean (SD) | Mean Change * |
95% CI | P vs. Baseline † | |||||
| 24-h Mean GH, μg/L |
Baseline | N=17 | 0.91 (0.65) | N=17 | 0.73 (0.41) | N=19 | 0.90 (0.61) | |||||||||
| 24 mo | N=17 | 1.32 (0.91) | 1.54 ‡ | 1.11 to 2.16 | 0.001 | N=17 | 0.70 (0.38) | 0.98 ‡ | 0.70 to 1.37 | >.99 | N=19 | 1.35 (0.77) | 1.64 ‡ | 1.20 to 2.25 | <0.001 | |
| IGF-I, μg/L |
Baseline | N=16 | 86 (41) | N=17 | 91 (35) | N=19 | 113 (59) | |||||||||
| 24 mo | N=16 | 133 (63) | 1.53 ‡ | 1.26 to 1.84 | <0.001 | N=17 | 90 (36) | 0.98 ‡ | 0.82 to 1.18 | >.99 | N=19 | 153 (66) | 1.42 ‡ | 1.20 to 1.69 | <0.001 | |
| FFM, kg [4-C] |
Baseline | N=17 | 50.7 (11.0) | N=17 | 48.0 (8.9) | N=19 | 49.0 (12.1) | |||||||||
| 24 mo | N=17 | 51.5 (11.5) | 0.8 | -0.7 to 2.2 | 0.30 | N=17 | 48.6 (9.1) | 0.6 | -0.9 to 2.0 | 0.74 | N=19 | 49.7 (12.3) | 0.7 | -0.7 to 2.1 | 0.38 | |
| FFM, kg [DXA] |
Baseline | N=17 | 50.9 (12.7) | N=17 | 49.9 (10.6) | N=19 | 49.2 (12.9) | |||||||||
| 24 mo | N=17 | 52.5 (12.6) | 1.6 | 0.6 to 2.6 | <0.001 | N=17 | 49.4 (10.3) | -0.5 | -1.5 to 0.6 | 0.54 | N=19 | 50.0 (12.8) | 0.9 | -0.1 to 1.8 | 0.026 | |
| T-Score for Limb Lean (TASM)/ht2 |
Baseline | N=17 | -1.9 (0.9) | N=17 | -1.9 (0.7) | N=19 | -1.8 (0.9) | |||||||||
| 24 mo | N=17 | -1.7 (0.8) | 0.25 | 0.02 to 0.48 | 0.006 | N=17 | -1.9 (0.7) | -0.001 | -0.231 to 0.229 | >.99 | N=19 | -1.8 (0.8) | 0.07 | -0.153 to 0.283 | >.99 | |
| AVF, cm2 [CT] |
Baseline | N=14 | 127.5 (59.5) | N=16 | 135.9 (63.2) | N=16 | 109.7 (47.4) | |||||||||
| 24 mo | N=14 | 125.5 (52.4) | -2.0 | -20.8 to 16.7 | >.99 | N=16 | 130.0 (59.0) | -6.0 | -23.5 to 11.6 | 0.89 | N=16 | 108.2 (45.2) | -1.4 | -18.9 to 16.1 | >.99 | |
| ASCF, cm2 [CT] |
Baseline | N=13 | 252.4 (95.9) | N=16 | 308.3 (106.1) | N=16 | 275.0 (128.6) | |||||||||
| 24 mo | N=13 | 269.2 (98.2) | 16.8 | -7.7 to 41.2 | 0.116 | N=16 | 301.1 (98.6) | -7.2 | -29.3 to 14.8 | 0.94 | N=16 | 280.0 (133.1) | 5.0 | -17.0 to 27.1 | >.99 | |
| Weight, |
Baseline | N=17 | 76.5 (12.1) | N=17 | 77.5 (10.9) | N=19 | 74.5 (13.4) | |||||||||
| 24 mo | N=17 | 79.2 (12.8) | 2.7 | 0.6 to 4.7 | 0.001 | N=17 | 77.0 (11.6) | -0.5 | -2.5 to 1.5 | >.99 | N=19 | 76.8 (14.0) | 2.3 | 0.4 to 4.2 | 0.002 | |
| Fat, kg [4-C] |
Baseline | N=17 | 25.8 (8.1) | N=17 | 29.5 (6.3) | N=19 | 25.5 (8.5) | |||||||||
| 24 mo | N=17 | 27.7 (8.1) | 1.9 | 0.3 to 3.5 | 0.016 | N=17 | 28.5 (7.1) | -1.0 | -2.6 to 0.6 | 0.34 | N=19 | 27.1 (8.9) | 1.6 | 0.1 to 3.1 | 0.033 | |
| Fat, kg [DXA] |
Baseline | N=17 | 25.1 (8.7) | N=17 | 27.6 (7.3) | N=19 | 25.0 (8.9) | |||||||||
| 24 mo | N=17 | 26.5 (9.0) | 1.4 | -0.1 to 2.9 | 0.062 | N=17 | 27.3 (7.7) | -0.3 | -1.8 to 1.2 | >.99 | N=19 | 26.5 (9.3) | 1.5 | 0.1 to 2.9 | 0.030 | |
| FBG, mmol/L [mg/dL] |
Baseline | N=17 | 5.7 (0.3) [102 (6)] | N=17 | 5.3 (0.4) [95 (7)] | N=19 | 5.4 (0.4) [98 (8)] | |||||||||
| 24 mo | N=17 | 5.9 (0.6) [107 (10)] | 0.3 [5] | -0.06 to 0.6 [-1 to 10] | 0.093 | N=17 | 5.3 (0.3) [95 (5)] | 0.06 [1] | -0.3 - 0.6 [-5-6)] | >0.99 | N=19 | 5.9 (0.5) [106 (9)] | 0.4 [8] | 0.2 to 0.7 [3 to13)] | 0.001 | |
| Quicki Index |
Baseline | N=17 | 0.35 (0.03) | N=17 | 0.36 (0.03) | N=19 | 0.36 (0.03) | |||||||||
| 24 mo | N=17 | 0.34 (0.04) | -0.014 | -0.030 to 0.002 | 0.028 | N=17 | 0.37 (0.04) | 0.003 | -0.012 to 0.019 | >.99 | N=19 | 0.35 (0.03) | -0.010 | -0.025 to 0.005 | 0.120 | |
| Total Cholesterol, mmol/L [mg/dL] |
Baseline | N=17 | 5.04 (0.86) [195 (33)] | N=17 | 4.61 (0.88) [178 (34)] | N=18 | 4.66 (0.85) [180 (33)] | |||||||||
| 24 mo | N=17 | 4.88 (0.78) [188 (30)] | -0.17 [-7] | -0.54 to 0.21 [-21 to 8] | 0.83 | N=17 | 4.59 (0.66) [177 (25)] | -0.02 [-0.8] | -0.39 to 0.36 [-15 to 14] | >.99 | N=18 | 4.79 (0.82) [185 (32)] | 0.13 [5] | -0.23 to 0.49 [-9 to19] | >.99 | |
| LDL Cholesterol, mmol/L [mg/dL] |
Baseline | N=17 | 3.31 (0.72) [128 (28)] | N=17 | 2.90 (0.75) [112 (29)] | N=18 | 2.89 (0.75) [112 (29)] | |||||||||
| 24 mo | N=17 | 2.96 (0.51) [114 (20)] | -0.35 [-14] | -0.69 to -0.01 [-27 to -0.4] | 0.042 | N=17 | 2.89 (0.56) [112 (22)] | -0.01 [-0.4] | -0.35 to 0.33 [-14 to 13] | >.99 | N=18 | 2.86 (0.69) [110 (27)] | -0.03 [-1] | -0.36 to 0.3 [-14 to12] | >.99 | |
| HDL Cholesterol, mmol/L [mg/dL] |
Baseline | N=17 | 1.32 (0.43) [51 (17)] | N=17 | 1.25 (0.38) [48 (15)] | N=18 | 1.32 (0.39) [51 (15)] | |||||||||
| 24 mo | N=17 | 1.42 (0.53) [55 (21)] | 0.11 [4] | -0.20 to 0.23 [-1 to 9] | 0.120 | N=17 | 1.34 (0.35) [52 (14)] | 0.09 (-0.03) [4 (-1)] | -0.03 to 0.21 [-1 to 8] | 0.23 | N=18 | 1.50 (0.53) [58 (21)] | 0.18 [7] | 0.06 to 0.3 [2 to 12] | 0.001 | |
Data presented are the arithmetic mean (SD) at baseline and 24 months.
Changes from baseline are the arithmetic difference with 95% confidence intervals, unless otherwise indicated.
Bonferroni-adjusted P values are for the difference from baseline to 24 months within the group.
GH and IGF-I data were transformed to the natural logarithmic scale before conducting the statistical analyses; results are reported as the ratio of geometric means (fold-changes from baseline) with upper and lower 95% confidence intervals.
FFM measured by 4-compartment (4-C) model and by DXA
AVF and ASCF areas from single-slice abdominal CT scan
TFM measured by 4-compartment (4-C) model and by DXA
Quicki Index is insulin sensitivity estimated from fasting glucose and insulin.
Abbreviations: GH = growth hormone; IGF-I = insulin-like growth factor-I; FFM = fat-free mass; TFM = total fat mass; AVF = abdominal visceral fat; ASCF = abdominal subcutaneous fat; FBG = fasting blood glucose; LDL = low density lipoprotein; HDL = high density lipoprotein