Effects of DS-8500a on glycemic and lipid parameters
| Placebo (n=33) | 10 mg DS-8500a (n=32) | 75 mg DS-8500a (n=34) | |||||||||
| Baseline | Day 28 | Change from baseline to day 28 | Baseline | Day 28 | Change from baseline to day 28 | LSM difference versus placebo | Baseline | Day 28 | Change from baseline to day 28 | LSM difference versus placebo | |
| 24-hour WMG (mmol/L) | 11.08±1.93 | 11.34±2.12 | 0.23 (−0.16 to –0.62) | 11.59±2.02 | 11.03±2.15 | −0.51 (−0.90 to −0.12)* | −0.74 (−1.29 to –0.19)†† | 11.26±2.47 | 10.42±2.08 | −0.82 (−1.20 to −0.43)*** | −1.05 (−1.59 to –0.50)††† |
| FPG (mmol/L) | 8.59±1.54 | 8.49±1.78 | −0.14 (−0.48 to 0.20) | 9.17±1.65 | 8.73±1.60 | −0.34 (−0.69 to 0.01) | −0.20 (−0.69 to 0.29) | 8.60±1.92 | 7.69±1.41 | −0.93 (−1.27 to −0.59)*** | −0.79 (−1.27 to –0.31)†† |
| 2-hour PPG after breakfast (mmol/L) | 14.07±2.55 | 14.20±2.80 | 0.03 (−0.63 to 0.69) | 14.85±2.55 | 13.92±3.01 | −0.83 (−1.50 to –0.16)* | −0.86 (−1.80 to 0.08) | 14.51±3.11 | 13.04±2.47 | −1.42 (−2.08 to −0.76)*** | −1.45 (−2.38 to –0.52)†† |
| 2-hour PPG after lunch (mmol/L) | 12.73±2.65 | 13.27±2.87 | 0.50 (−0.14 to 1.13) | 13.72±2.74 | 13.07±3.23 | −0.56 (−1.21 to 0.08) | −1.06 (−1.97 to –0.15)† | 12.87±3.06 | 12.03±2.96 | −0.82 (−1.45 to −0.19)* | −1.32 (−2.21 to –0.42)†† |
| 2-hour PPG after dinner (mmol/L) | 14.23±2.28 | 14.99±2.48 | 0.68 (0.10 to 1.26)* | 15.05±2.63 | 14.59±2.89 | −0.36 (−0.95 to 0.23) | −1.04 (−1.87 to –0.21)† | 14.46±2.58 | 14.01±2.31 | −0.53 (−1.10 to 0.05) | −1.21 (−2.03 to –0.39)†† |
| Fasting plasma insulin (pmol/L) | 46.6±27.5 | 45.9±24.8 | −0.41 (−4.85 to 4.03) | 41.5±17.7 | 39.7±19.6 | −2.17 (−6.68 to 2.34) | −1.76 (−8.10 to 4.58) | 44.5±26.5 | 43.1±29.3 | −1.41 (−5.85 to 3.02) | −1.00 (−7.28 to 5.27) |
| Fasting plasma C-peptide (nmol/L) | 0.594±0.229 | 0.608±0.224 | 0.014 (−0.018 to 0.045) | 0.557±0.144 | 0.558±0.155 | 0.002 (−0.030 to 0.034) | −0.011 (−0.056 to 0.034) | 0.595±0.216 | 0.583±0.284 | −0.012 (−0.043 to 0.019) | −0.026 (−0.070 to 0.019) |
| Insulin AUC0–4h (pmol/L·h) | 737.4±448.4 | 729.1±421.0 | −3.52 (−52.05 to 45.01) | 629.9±311.8 | 607.5±278.1 | −33.25 (−82.74 to 16.25) | −29.73 (−99.21 to 39.76) | 735.1±462.3 | 775.3±424.4 | 36.67 (−11.88 to 85.22) | 40.19 (−28.37 to 108.8) |
| C-peptide AUC0–4h (nmol/L·h) | 6.05±2.09 | 6.19±2.00 | 0.147 (−0.105 to 0.399) | 5.63±1.54 | 5.73±1.56 | 0.080 (−0.178 to 0.337) | −0.067 (−0.428 to 0.294) | 6.15±2.11 | 6.75±2.26 | 0.569 (0.316, 0.821)** | 0.422 (0.065 to 0.778)† |
| Glucose AUC0–4h (nmol/L·h) | 50.52±7.99 | 50.98±9.07 | 0.21 (−1.73 to 2.14) | 53.32±8.80 | 50.37±9.62 | −2.59 (−4.57 to –0.62)* | −2.80 (−5.58 to –0.03)† | 51.37±10.53 | 46.92±8.59 | −4.42 (−6.35 to −2.49)** | −4.63 (−7.36 to –1.89)† |
| Insulin AUC0–4h/glucose AUC0–4h | 15.32±10.76 | 15.26±10.69 | 0.002 (−0.005 to 0.009) | 12.26±6.73 | 12.67±6.38 | 0.010 (0.003 to 0.017)* | 0.008 (−0.002 to 0.017) | 14.98±9.39 | 17.29±10.21 | 0.023 (0.017 to 0.030)** | 0.021 (0.012 to 0.031)†† |
| C-peptide AUC0–4h/glucose AUC0–4h | 0.124±0.051 | 0.127±0.053 | −0.003 (−1.190 to 1.162) | 0.109±0.038 | 0.119±0.042 | 0.307 (−0.894 to 1.508) | 0.321 (−1.368 to 2.009) | 0.124±0.046 | 0.149±0.056 | 2.121 (0.946 to 3.296)** | 2.135 (0.476 to 3.794)† |
| TC (mmol/L) | 4.96±0.68 | 4.86±0.70 | −0.111 (−0.253 to 0.029) | 5.06±0.80 | 4.91±0.82 | −0.154 (−0.298 to –0.012)* | −0.043 (−0.244 to 0.158) | 5.15±0.84 | 4.63±0.82 | −0.528 (−0.669 to −0.387)** | −0.417 (−0.617 to –0.216)†† |
| HDL-C (mmol/L) | 1.15±0.29 | 1.12±0.30 | −0.025 (−0.055 to 0.059) | 1.13±0.27 | 1.15±0.25 | 0.015 (−0.016 to 0.046) | 0.039 (−0.004 to 0.083) | 1.10±0.26 | 1.25±0.28 | 0.141 (0.110 to 0.171)** | 0.166 (0.122 to 0.209)†† |
| LDL-C (mmol/L) | 3.28±0.64 | 3.12±0.68 | −0.161(−0.299 to –0.024)* | 3.25±0.73 | 3.21±0.76 | −0.044 (−0.184 to 0.096) | 0.117 (−0.079 to 0.313) | 3.35±0.65 | 2.96±0.75 | −0.387 (−0.525 to −0.249)** | −0.225 (−0.420 to –0.031)† |
| Triglycerides (mmol/L) | 1.72±1.03 | 1.89±1.27 | 0.117 (−0.094 to 0.329) | 1.97±1.09 | 1.71±0.92 | −0.237 (−0.451 to −0.022) | −0.354 (−0.656 to –0.052)† | 1.96±1.21 | 1.33±0.68 | −0.615 (−0.826 to −0.403)** | −0.732 (−1.032 to –0.432)†† |
Results are presented as the mean±SD, LSM (95% CI) versus baseline, or LSM (95% CI) versus placebo.
*p< 0.05, **p<0.01, ***p<0.001 versus baseline; †p<0.05, ††p<0.01, †††p<0.001 versus placebo.
AUC0–4h, area under the concentration–time curve from 0 to 4 hours; FPG, fasting plasma glucose; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; LSM, least squares mean; PPG, postprandial plasma glucose; TC, total cholesterol; WMG, weighted mean glucose.