Table 2.
Pharmacodynamics
| Placebo (n = 29) | 25 mg DS‐8500a (n = 28) | 75 mg DS‐8500a (n = 27) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Day –1 | Day 28 | Change from day −1 to day 28 | Day −1 | Day 28 | Change from day −1 to day 28 | LSM difference vs placebo | Day −1 | Day 28 | Change from day −1 to day 28 | LSM difference vs placebo (full analysis set) | |
| 2 h‐PPG after breakfast (mg/dL) | 220.5 | 223.1 | 1.4 | 234.9 | 209.4 | −23.5*** | −24.8†† | 222.4 | 205.0 | −18.2** | −19.6† |
| 2 h‐PPG after lunch (mg/dL) | 216.1 | 213.4 | −5.3 | 223.8 | 197.2 | −26.2*** | −20.9† | 229.2 | 205.2 | −21.5*** | −16.2 |
| 2 h‐PPG after dinner (mg/dL) | 234.2 | 233.7 | −1.7 | 239.4 | 227.1 | −12.1* | −10.4 | 242.3 | 225.1 | −16.1** | −14.4 |
| Fasting insulin (μU/mL) | 7.91 | 7.59 | −0.27 | 6.53 | 6.30 | −0.26 | 0.01 | 7.19 | 6.63 | −0.56 | −0.29 |
| Fasting C‐peptide (ng/mL) | 1.44 | 1.43 | −0.01 | 1.30 | 1.29 | −0.02 | −0.01 | 1.47 | 1.44 | −0.03 | −0.02 |
| Glucose AUC0–4 h (mg/dL · h) | 827.6 | 829.2 | −1.39 | 862.57 | 783.72 | −74.16*** | −72.77†† | 832.86 | 756.34 | −78.28*** | −76.89††† |
| Insulin AUC0–4 h (μU/mL · h) | 139.5 | 134.0 | −4.3 | 118.1 | 114.4 | −5.3 | −1.0 | 133.8 | 131.8 | −1.5 | 2.8 |
| C‐peptide AUC0–4 h (ng/mL · h) | 14.97 | 14.6 | −0.36 | 13.98 | 13.86 | −0.16 | 0.21 | 15.26 | 15.56 | 0.32 | 0.69 |
| PYY AUC0–4 h (pg/mL · h) | 461.8 | 447.0 | −23.7 | 464.6 | 469.4 | −2.8 | 20.9 | 520.5 | 549.4 | 46.1* | 69.8† |
| Active GLP‐1 AUC0–4 h (pmol/L · h) | 41.9 | 43.4 | 0.5 | 49.6 | 54.2 | 5.0 | 4.4 | 51.0 | 53.5 | 3.1 | 2.5 |
| Total GLP‐1 AUC0–4 h (pmol/L · h) | 48.96 | 48.43 | −2.2 | 53.0 | 55.01 | 1.3 | 3.5 | 66.7 | 63.71 | −0.4 | 1.8 |
| Glucagon AUC0–4 h (pg/mL · h) | 522.8 | 521.7 | −1.0 | 506.5 | 512.9 | 2.8 | 3.8 | 528.5 | 528.0 | 1.9 | 2.8 |
| GIP AUC0–4 h (pg/mL · h) | 1047.4 | 978.7 | −74.4 | 996.8 | 1292.7 | 281.4*** | 355.8††† | 1193.2 | 1486.7 | 315.6*** | 390.0††† |
| Insulin AUC0–4 h/glucose AUC0–4 h | 21.45 | 20.36 | −1.09 | 17.93 | 19.07 | 1.14 | 1.69 | 21.29 | 22.52 | 1.23 | 2.30 |
| C‐peptide AUC0–4 h/glucose AUC0–4 h | 0.110 | 0.107 | −0.003 | 0.100 | 0.109 | 0.009* | 0.011 | 0.114 | 0.127 | 0.013** | 0.016†† |
Data are presented as the change from baseline to day 28, or least squares mean (LSM) difference vs placebo. *P < 0.05, **P < 0.01 and ***P < 0.001 vs baseline; † P < 0.05, †† P < 0.01 and ††† P < 0.001 vs placebo. AUC0–4 h, area under the concentration‐time curve from 0 to 4 h; GIP, glucose‐dependent insulinotropic peptide; GLP‐1, glucagon‐like peptide‐1; PYY, peptide YY.