Table 2.
Biomarkers
| PBO N = 19 |
RETA 1 mg N = 20 |
RETA 4 mg N = 19 |
RETA 8 mg N = 22 |
RETA 12 mg N = 18 |
|
|---|---|---|---|---|---|
| Fasting insulin | |||||
| Baseline, mU l−1 | 18.3 (2.0) | 18.9 (2. 5) | 22.0 (1.9) | 21.3 (1.8) | 20.2 (2.9) |
| CFB week 24, % | −7.5 (8.1) | −31.6 (9.0) | −40.8 (6.2) | −37.3 (5.9) | −47.7 (5.8) |
| P value | – | 0.058 | 0.001 | 0.002 | <0.001 |
| Liver fat correlation week 24 | 0.381 | ||||
| P value | <0.001 | ||||
| CFB week 48, % | −12.5 (10.2) | −37.5 (7.8) | −43.7 (9.4) | −52.6 (6.3) | −70. 9 (5.2) |
| P value | 0.049 | 0.029 | 0.001 | <0.001 | |
| Liver fat correlation week 48 | 0.612 | ||||
| P value | <0.001 | ||||
| C-peptide | |||||
| Baseline, µg l−1 | 2.4 (0.2) | 2.6 (0.2) | 2.6 (0.2) | 2.9 (0.2) | 2.6 (0.2) |
| CFB week 24, % | −5.3 (6.8) | −26.3 (6.8) | −32.8 (4.9) | −28.8 (4.9) | −29.1 (6.8) |
| P value | – | 0.036 | 0.001 | 0.005 | 0.017 |
| Liver fat correlation week 24 | 0.389 | ||||
| P value | <0.001 | ||||
| CFB week 48, % | −13.3 (4.8) | −32.4 (5.8) | −33.4 (8.7) | −39.2 (4.9) | −50.5 (5.7) |
| P value | 0.019 | 0.056 | <0.001 | <0.001 | |
| Liver fat correlation week 48 | 0.514 | ||||
| P value | <0.001 | ||||
| HOMA2-IR (C-peptide) | |||||
| Baseline | 1.8 (0.1) | 1. 9 (0.2) | 2.0 (0.1) | 2.1 (0.2) | 1.9 (0.2) |
| CFB week 24, % | −6.1 (7.2) | −28.3 (6.8) | −34.8 (6.1) | −30.9 (5.5) | −33.7 (6.4) |
| P value | – | 0.030 | 0.002 | 0.006 | 0.005 |
| Liver fat correlation week 24 | 0.404 | ||||
| P value | <0.001 | ||||
| CFB week 48, % | −16.2 (5.6) | −33.7 (6.3) | −26.3 (7.5) | −42.3 (4.6) | −54.5 (5.9) |
| P value | – | 0.051 | 0.278 | <0.001 | <0.001 |
| Liver fat correlation week 48 | 0.510 | ||||
| P value | <0.001 | ||||
| HOMA2-IR (insulin) | |||||
| Baseline | 2.4 (0.3) | 2.4 (0.3) | 2.7 (0.2) | 2.7 (0.2) | 2.3 (0.3) |
| % CFB week 24 | −6.7 (8.5) | −30.5 (8.6) | −43.9 (5.3) | −35.8 (5.7) | −48.9 (5.8) |
| P value | – | 0.056 | <0.001 | 0.003 | <0.001 |
| Liver fat correlation week 24 | 0.381 | ||||
| P value | 0.001 | ||||
| CFB week 48, % | −11.1 (9.5) | −36.3 (8.6) | −49.4 (5.9) | −52.4 (6.8) | −69.3 (6.2) |
| P value | – | 0.053 | <0.001 | <0.001 | <0.001 |
| Liver fat correlation week 48 | 0.575 | ||||
| P value | <0.001 | ||||
| Adiponectin | |||||
| Baseline, mg l−1 | 4.2 (0.5) | 3.8 (0.4) | 4.2 (0.7) | 4.1 (0.5) | 3.6 (0.4) |
| CFB week 24, % | 3.4 (4.8) | 15.7 (4.7) | 29.8 (10.8) | 33.5 (5.3) | 44.0 (7.8) |
| P value | – | 0.069 | 0.017 | <0.001 | <0.001 |
| Liver fat correlation week 24 | −0.568 | ||||
| P value | <0.001 | ||||
| CFB week 48, % | 12.8 (8.4) | 22.5 (10.5) | 56.9 (13.0) | 99.3 (19.6) | 59.3 (19.8) |
| P value | 0.474 | 0.003 | <0.001 | 0.014 | |
| Liver fat correlation week 48 | −0.602 | ||||
| P value | <0.001 | ||||
| Leptin | |||||
| Baseline, µg l−1 | 39.4 (5.2) | 24.0 (6.5) | 30.6 (4.3) | 31.9 (4.1) | 42.4 (4.6) |
| CFB week 24, % | 17.7 (10.6) | −8.3 (11.8) | −29.0 (8.8) | −41.4 (8.7) | −55.8 (7.8) |
| P value | – | 0.121 | 0.001 | <0.001 | <0.001 |
| Liver fat correlation week 24 | 0.413 | ||||
| P value | <0.001 | ||||
| CFB week 48, % | −0.003 (31.8) | −30.3 (14.9) | −41.3 (11.9) | −63.6 (8.1) | −68.0 (8.6) |
| P value | – | 0.361 | 0.173 | 0.011 | 0.006 |
| Liver fat correlation week 48 | 0.524 | ||||
| P value | <0.001 | ||||
| Triglycerides | |||||
| Baseline, mg dl−1 | 143.5 (14.5) | 139.8 (15.7) | 155.8 (15.5) | 130.0 (12.1) | 141.3 (17.4) |
| CFB week 24, % | −0.4 (4.6) | −15.8 (6.1) | −39.5 (7.2) | −35.4 (6.1) | −40.0 (4.5) |
| P value | – | 0.050 | <0.001 | <0.001 | <0.001 |
| Liver fat correlation week 24 | 0.499 | ||||
| P value | <0.001 | ||||
| CFB week 48, % | −4.1 (6.3) | −21.8 (5.4) | −37.0 (6.2) | −41.1 (5.4) | −49.4 (5.7) |
| P value | – | 0.030 | <0.001 | <0.001 | <0.001 |
| Liver fat correlation week 48 | 0.432 | ||||
| P value | 0.004 | ||||
| β-Hydroxybutyrate | |||||
| Baseline, mg dl−1 | 1.1 (0.1) | 1.0 (0.1) | 1.0 (0.1) | 1.0 (0.1) | 1.3 (0.2) |
| CFB week 24, % | 2.6 (19.5) | 25.2 (17.0) | 92.9 (36.6) | 78.0 (32.2) | 181.2 (54.5) |
| P value | – | 0.399 | 0.023 | 0.037 | <0.001 |
| Liver fat correlation week 24 | −0.335 | ||||
| P value | 0.003 | ||||
| CFB week 48, % | −2.5 (27.1) | 33.3 (20.7) | 30.3 (25.7) | 46.8 (26.2) | 160.5 (46.3) |
| P value | – | 0.336 | 0.414 | 0.225 | 0.003 |
| Liver fat correlation week 48 | −0.238 | ||||
| P value | 0.129 | ||||
| FGF21 | |||||
| Baseline, ng l−1 | 309.4 (48.6) | 431.3 (62.7) | 361.3 (73.8) | 384.1 (47.4) | 274.2 (36.8) |
| CFB week 24, % | −17.2 (11.5) | −26.5 (10.4) | −52.2 (9.4) | −65.7 (4.8) | −54.2 (10.2) |
| P value | – | 0.573 | 0.024 | <0.001 | 0.021 |
| Liver fat correlation week 24 | 0.473 | ||||
| P value | <0.001 | ||||
| CFB week 48, % | 9.7 (16.5) | −26.7 (18.7) | −46.3 (14.6) | −51.1 (13.1) | −38.7 (19.9) |
| P value | 0.172 | 0.022 | 0.008 | 0.105 | |
| Liver fat correlation week 48 | 0.485 | ||||
| P value | 0.001 | ||||
| Free fatty acids | |||||
| Baseline, mEq l−1 | 0.6 (0.1) | 0.5 (0.1) | 0.5 (0.04) | 0.5 (0.05) | 0.6 (0.05) |
| CFB week 24, % | 12.6 (6.1) | −0.03 (8.0) | −0.03 (6.7) | 8.6 (9.7) | 1.6 (7.6) |
| P value | – | 0.215 | 0.169 | 0.726 | 0.270 |
| Liver fat correlation week 24 | 0.079 | ||||
| P value | 0.504 | ||||
| CFB week 48, % | 1.0 (9.9) | −12.2 (9.3) | −16.8 (11.6) | −25.2 (10.7) | 7.2 (12.0) |
| P value | – | 0.350 | 0.259 | 0.082 | 0.692 |
| Liver fat correlation week 48 | 0.091 | ||||
| P value | 0.567 | ||||
| K-18a | |||||
| Baseline, U l−1 | 275.3 (26.6) | 310.9 (45.3) | 263.5 (16.9) | 281.1 (35.6) | 305.5 (61.5) |
| CFB week 24, % | −18.3 (5.1) | −13.0 (12.0) | −33.2 (10.3) | −35.5 (7.4) | −27.9 (7.2) |
| P value | – | 0.705 | 0.204 | 0.0478 | 0.296 |
| Liver fat correlation week 24 | 0.232 | ||||
| P value | 0.061 | ||||
| CFB week 48, % | −28.0 (6.6) | −41.0 (5.7) | −41.2 (15.3) | −49.6 (7.1) | −47.4 (5.0) |
| P value | – | 0.140 | 0.434 | 0.022 | 0.016 |
| Liver fat correlation week 48 | 0.152 | ||||
| P value | 0.361 | ||||
| Pro-C3a,b | |||||
| Baseline, µg l−1 | 12.8 (0.6) | 14.2 (1.0) | 13.8 (0.9) | 12.9 (0.9) | 14.0 (1.2) |
| CFB week 24, % | −5.7 (2.5) | −11.9 (6.05) | −23.3 (3.5) | −22.7 (4.4) | −26.4 (2.3) |
| P value | – | 0.359 | <0.001 | 0.001 | <0.001 |
| Liver fat correlation week 24 | 0.426 | ||||
| P value | <0.001 | ||||
| CFB week 48, % | −0.3 (3.9) | −21.6 (4.6) | −21.1 (2.4) | −15.4 (4.3) | −15.5 (7.8) |
| P value | – | <0.001 | <0.001 | 0.010 | 0.089 |
| Liver fat correlation week 48 | 0.301 | ||||
| P value | 0.067 | ||||
| ALT | |||||
| Baseline, IU l−1 | 31.6 (2.1) | 29.1 (3.1) | 35.5 (3.0) | 33.9 (3.2) | 34.4 (4.0) |
| CFB week 24, % | −13.5 (4.3) | −21.0 (6.2) | −30.3 (6.6) | −25.8 (9.0) | −21.6 (11.3) |
| P value | – | 0.329 | 0.044 | 0.245 | 0.521 |
| Liver fat correlation week 24 | 0.208 | ||||
| P value | 0.069 | ||||
| CFB week 48, % | −2.9 (11.6) | −21.4 (6.0) | −33.6 (5.4) | −24.0 (8.7) | −15.8 (11.6) |
| P value | – | 0.134 | 0.009 | 0.141 | 0.432 |
| Liver fat correlation week 48 | 0.029 | ||||
| P value | 0.854 | ||||
| AST | |||||
| Baseline, IU l−1 | 24.5 (1.2) | 23.9 (1.8) | 23.1 (1.2) | 24.6 (1.6) | 25.0 (2.1) |
| CFB week 24, % | −7.2 (3.2) | −13.0 (5.6) | −19.9 (5.0) | −19.3 (6.1) | −18.2 (6.9) |
| P value | – | 0.380 | 0.042 | 0.096 | 0.164 |
| Liver fat correlation week 24 | 0.241 | ||||
| P value | 0.035 | ||||
| CFB week 48, % | 18.3 (19.4) | −5.4 (5.6) | −21.8 (5.6) | −16.6 (6.7) | −1.5 (15.5) |
| P value | – | 0.196 | 0.023 | 0.052 | 0.424 |
| Liver fat correlation week 48 | 0.190 | ||||
| P value | 0.229 | ||||
| FIB-4 index | |||||
| Baseline | 0.7 (0.1) | 0.9 (0.1) | 0.7 (0.04) | 0.9 (0.1) | 0.7 (0.1) |
| CFB week 24, % | −7.2 (4.4) | −2.4 (6.1) | 11.2 (8.2) | −9.4 (4.9) | −4.2 (6.5) |
| P value | – | 0.535 | 0.052 | 0.746 | 0.698 |
| Liver fat correlation week 24 | −0.041 | ||||
| P value | 0.728 | ||||
| CFB week 48, % | 31.5 (33.0) | 4.1 (6.0) | 11.8 (11.6) | −1.2 (7.4) | 25.9 (30.4) |
| P value | – | 0.431 | 0.567 | 0.327 | 0.900 |
| Liver fat correlation week 48 | 0.122 | ||||
| P value | 0.440 | ||||
| ELF testa | |||||
| Baseline | 7.8 (0.2) | 8.3 (0.2) | 8.2 (0.1) | 8.2 (0.2) | 8.0 (0.3) |
| CFB week 24, % | 9.2 (2.5) | 5.9 (2.3) | −0.6 (2.8) | 4.8 (1.6) | 4.5 (1.6) |
| P value | – | 0.317 | 0.007 | 0.135 | 0.121 |
| Liver fat correlation week 24 | 0.050 | ||||
| P value | 0.691 | ||||
| CFB week 48, % | 8.3 (2.5) | 3.5 (1.5) | 5.3 (3.2) | 8.0 (1.8) | 8.6 (2.6) |
| P value | – | 0.105 | 0.458 | 0.933 | 0.926 |
| Liver fat correlation week 48 | −0.133 | ||||
| P value | 0.428 | ||||
Data are LSMs (s.e.m.) or geometric mean (s.e.m.) from analysis of variance. P values under % CFB are LSMs comparison versus PBO by using two-sided z-tests without multiplicity adjustment. Correlations are Spearman coefficients and P values. N, number of participants; n, number of observations.
an = 89.
bPro-C3 measured with the second-generation enzyme-linked immunosorbent assay (ELISA) corrected to correspond to the first-generation ELISA to enable comparisons with published literature (correction factor of 0.152).