Table 2.
Baseline Clinical and Biochemical Status and Change From Baseline During Study, by Treatment Group
| Variable | Placebo
|
Salsalate
|
Difference in Change (95% CI)* | P Value† | ||
|---|---|---|---|---|---|---|
| Mean Baseline Value (SD) | Mean Change From Baseline (95% CI) | Mean Baseline Value (SD) | Mean Change From Baseline (95% CI) | |||
| Vital signs | ||||||
|
| ||||||
| Weight, kg | 95.4 (22.3) | −0.40 (−0.76 to −0.04) | 97.0 (22.7) | 0.94 (0.59 to 1.30) | 1.34 (0.85 to 1.84) | <0.001 |
|
| ||||||
| Heart rate, beats/min | 72 (10) | 1.1 (0.2 to 2.0) | 74 (10) | −0.7 (−1.6 to 0.2) | −1.8 (−3.0 to 0.5) | 0.007 |
|
| ||||||
| Systolic BP, mm Hg | 126.4 (13.9) | 0.6 (−0.6 to 1.8) | 125.9 (12.9) | 2.1 (1.0 to 3.3) | 1.6 (−0.1 to 3.2) | 0.063 |
|
| ||||||
| Diastolic BP, mm Hg | 76.9 (8.0) | 0.5 (−0.3 to 1.2) | 76.0 (8.8) | 0.8 (0.1 to 1.6) | 0.4 (−0.7 to 1.4) | 0.49 |
| Endocrine | ||||||
|
| ||||||
| HbA1c level, % | 7.7 (0.7) | 0.04 (−0.07 to 0.15) | 7.7 (0.7) | −0.33 (−0.44 to −0.22) | −0.37 (−0.53 to −0.21) | <0.001 |
|
| ||||||
| Fasting glucose level | ||||||
| mmol/L | 8.30 (2.09) | 0.11 (−0.11 to 0.33) | 8.49 (2.14) | −0.72 (−0.94 to −0.51) | −0.83 (−1.14 to −0.53) | <0.001 |
| mg/dL | 150 (38) | 2.0 (−1.9 to 5.9) | 153 (39) | −13.1 (−16.9 to −9.2) | −15.0 (−20.5 to −9.6) | <0.001 |
|
| ||||||
| Insulin level, pmol/L | 87.4 (56.1 to 141.2)‡ | 2.9 (−4.0 to 10.4)§ | 96.1 (69.5 to 152.4)‡ | 15.2 (6.9 to 24.0)§ | 10.5 (0.3 to 21.8) | 0.042§ |
|
| ||||||
| C-peptide level | ||||||
| nmol/L | 0.92 (0.42) | 0.01 (−0.03 to 0.05) | 1.00 (0.43) | −0.07 (−0.11 to −0.03) | −0.08 (−0.14 to −0.02) | 0.009 |
| ng/mL | 2.76 (1.25) | 0.03 (−0.10 to 0.16) | 2.94 (1.28) | −0.21 (−0.34 to −0.08) | −0.24 (−0.42 to −0.06) | 0.009 |
| Lipids | ||||||
|
| ||||||
| Total cholesterol level | ||||||
| mmol/L | 4.29 (1.04) | 0.00 (−0.08 to 0.09) | 4.27 (1.09) | 0.22 (0.14 to 0.31) | 0.22 (0.10 to 0.34) | <0.001 |
| mg/dL | 166 (40) | 0.0 (−3.3 to 3.3) | 165 (42) | 8.6 (5.4 to 11.9) | 8.6 (4.0 to 13.2) | <0.001 |
|
| ||||||
| HDL cholesterol level | ||||||
| mmol/L | 1.26 (0.33) | 0.03 (0.01 to 0.05) | 1.20 (0.32) | 0.02 (0.00 to 0.04) | −0.01 (−0.04 to 0.02) | 0.50 |
| mg/dL | 48.65 (12.74) | 1.16 (0.39 to 1.93) | 46.33 (12.36) | 0.77 (0.00 to 1.54) | −0.39 (−1.54 to 0.77) | 0.50 |
|
| ||||||
| LDL cholesterol level | ||||||
| mmol/L | 2.64 (0.82) | −0.02 (−0.10 to 0.05) | 2.64 (0.89) | 0.27 (0.20 to 0.34) | 0.29 (0.19 to 0.40) | <0.001 |
| mg/dL | 102 (32) | −0.8 (−3.7 to 2.1) | 102 (35) | 10.4 (7.6 to 13.3) | 11.2 (7.2 to 15.3) | <0.001) |
|
| ||||||
| Triglyceride level | ||||||
| mmol/L | 1.51 (1.07 to 2.19)‡ | −0.05 (−0.11 to 0.02)§ | 1.56 (1.12 to 2.20)‡ | −0.18 (−0.24 to −0.12)§ | −0.14 (−0.22 to −0.05)§ | 0.002§ |
| mg/dL | 134 (95 to 194)‡ | −4.4 (−9.7 to −1.8)§ | 138 (99 to 195)‡ | −15.9 (−21.2 to −10.6)§ | −12.4 (−19.5 to −4.4)§ | 0.002§ |
|
| ||||||
| FFA level, mmol/L | 0.48 (0.23) | −0.02 (−0.04 to 0.01) | 0.50 (0.22) | −0.00 (−0.03 to 0.02) | 0.02 (−0.02 to 0.05) | 0.41 |
|
| ||||||
| Total–HDL cholesterol ratio | 3.58 (1.07) | −0.10 (−0.19 to −0.01) | 3.75 (1.16) | 0.21 (0.12 to 0.30) | 0.31 (0.19 to 0.44) | <0.001 |
| Renal | ||||||
|
| ||||||
| Creatinine level | ||||||
| μmol/L | 73.5 (14.9) | −0.5 (−1.7 to 0.7) | 72.4 (15.0) | 1.8 (0.6 to 3.0) | 2.3 (0.6 to 4.0) | 0.007 |
| mg/dL | 0.83 (0.17) | −0.01 (−0.02 to 0.01) | 0.82 (0.17) | 0.02 (0.01 to 0.03) | 0.03 (0.01 to 0.05) | 0.007 |
|
| ||||||
| MDRD eGFR, mL/min per 1.73 m2 | 99.0 (19.9) | 1.2 (−0.9 to 3.3) | 101.6 (21.7) | −0.8 (−2.8 to 1.3) | −2.0 (−4.9 to 0.9) | 0.178 |
|
| ||||||
| Cystatin C level, mg/L | 71.7 (15.1) | −1.2 (−2.6 to 0.2) | 72.2 (14.6) | −1.9 (−3.2 to −0.5) | −0.7 (−2.6 to 1.3) | 0.50 |
|
| ||||||
| Cystatin C–based eGFR, mL/min per 1.73 m2 | 22.7 (4.4) | 0.4 (−0.05 to 0.8) | 22.4 (4.2) | 0.71 (0.3 to 1.1) | 0.3 (−0.3 to 0.9) | 0.28 |
|
| ||||||
| Uric acid level, μmol/L | 349 (90) | −10.7 (−21.6 to 0.28) | 371 (87) | −71.3 (−82.1 to −60.5) | −60.7 (−76.0 to −45.3) | <0.001 |
|
| ||||||
| ACR, μg/mg | 8.0 (5.0 to 13.0)‡ | 1.1 (1.0 to 1.2) | 7.0 (5.0 to 13.0)‡ | 2.6 (2.3 to 2.8) | 2.3 (2.0 to 2.7) | <0.001§ |
| Hepatic | ||||||
|
| ||||||
| ALT level, U/L | 0.35 (0.27 to 0.52)‡ | 0.00 (−0.10 to 0.05)‡ | 0.33 (0.25 to 0.52)‡ | −0.03 (−0.10 to 0.03)‡ | 0.068∥ | |
|
| ||||||
| AST level, U/L | 0.32 (0.25 to 0.42)‡ | 0.00 (−0.05 to 0.05)‡ | 0.32 (0.25 to 0.40)‡ | 0.00 (−0.05 to 0.03)‡ | 0.81∥ | |
|
| ||||||
| GGT level, U/L | 0.45 (0.32 to 0.72)‡ | 0.00 (−0.12 to 0.05)‡ | 0.43 (0.32 to 0.60)‡ | −0.03 (−0.12 to 0.03)‡ | <0.001∥ | |
|
| ||||||
| Albumin level, g/L | 44.0 (2.9) | −0.03 (−0.3 to 0.2) | 43.7 (2.7) | −1.9 (−2.2 to −1.7) | −1.9 (−2.3 to −1.5) | <0.001 |
| Other | ||||||
|
| ||||||
| Hematocrit, % | 41.2 (4.1) | −0.19 (−0.48 to 0.10) | 41.3 (4.3) | 0.60 (0.31 to 0.88) | 0.79 (0.39 to 1.19) | <0.001 |
|
| ||||||
| Leukocyte count, × 109 cells/L | 6.60 (1.93) | 0.00 (−0.14 to 0.15) | 7.00 (2.09) | −0.63 (−0.77 to −0.48) | −0.63 (−0.83 to −0.43) | <0.001 |
|
| ||||||
| Neutrophil count, × 109 cells/L | 2.12 (0.72) | −0.02 (−0.07 to 0.04) | 2.16 (0.67) | −0.27 (−0.32 to 0.21) | −0.25 (−0.32 to −0.18) | 0.001 |
|
| ||||||
| Lymphocyte count, × 109 cells/L | 3.89 (1.44) | −0.4 (−0.17 to 0.10) | 4.31 (1.70) | −0.36 (−0.50 to −0.23) | −0.32 (−0.52 to −013) | <0.001 |
|
| ||||||
| Adiponectin level, μg/mL | 3.98 (3.02 to 6.00)‡ | 0.25 (0.08 to 0.43)§ | 4.17 (3.06 to 5.86)‡ | 1.51 (1.29 to 1.74)§ | 1.16 (0.88 to 1.47)§ | <0.001§ |
|
| ||||||
| hs-CRP level, nmol/L | 33.1 (16.3 to 58.8)‡ | −0.68 (−3.51 to 2.45)§ | 32.5 (14.7 to 67.7)‡ | −2.45 (−5.06 to 0.43)§ | −1.80 (−5.51 to 2.46)§ | 0.39§ |
|
| ||||||
| TNF-α level, pg/mL | 1.69 (0.79) | 0.00 (−0.07 to 0.07)§ | 1.83 (2.31) | 0.05 (−0.02 to 0.11)§ | 0.05 (−0.05 to 0.15)§ | 0.32§ |
|
| ||||||
| TNF–receptor 1 level, ng/mL | 3.06 (0.72) | −0.04 (−0.11 to 0.03)§ | 3.04 (0.83) | −0.06 (−0.13 to 0.01)§ | −0.00 (−0.13 to 0.08)§ | 0.62§ |
|
| ||||||
| TNF–receptor 2 level, ng/mL | 8.21 (1.95) | −0.21 (−0.41 to −0.01)§ | 8.14 (2.20) | −0.05 (−0.25 to 0.15)§ | 0.16 (−0.13 to 0.46)§ | 0.28§ |
ACR = albumin–creatinine ratio; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BP = blood pressure; eGFR = estimated glomerular filtration rate; FFA = free fatty acid; GGT= γ-glutamyltransferase; HbA1c = hemoglobin A1c; HDL = high-density lipoprotein; hs-CRP = high-sensitivity C-reactive protein; LDL = low-density lipoprotein; MDRD = Modification of Diet in Renal Disease; TNF = tumor necrosis factor.
*
Salsalate minus placebo.
†
Unless otherwise noted, P values are mixed-model tests of the overall treatment effect after adjustment for clinical and follow-up time over the 48-wk study.
‡
Median (25th–75th percentiles).
§
Test based on natural log-transformation, results are back-transformed, and the change ratio is multiplied by the group mean.
∥
Wilcoxon 2-sample test; 2-sided P > |Z|. The probability test statistic was calculated using the Z-score from a standard normal table; there are no estimates of a difference in change when rank testing was used.