Table 4.
Final population parameter estimates from the final model
| Parameter estimate (RSE%) | IIV a (RSE%) [Shrinkage%] | |
|---|---|---|
| Weight | ||
| WGT t 1/2 (days) | 73.9 (5) | – |
| Baseline WGT (kg) | 102 (1) | 16.1 (4) [0] |
| β‐cell function | ||
| Baseline β‐cell function, logistic function ( b0 ): | ||
| Study 1 | –0.298 (31) | 1.13 (13) [9.5] |
| Studies 2 and 3 | 0.677 (17) | |
| rB , rate of β‐cell function loss per year, logistic function | 0.209 (fixed) | 0.408 (16) [19] |
| EFBT , treatment effect on β‐cell function (%) | 0.0781 (31) | 0.053 (12) [15.8] |
| Insulin sensitivity | ||
| s0 , baseline insulin sensitivity, logistic function | 0.963 (5) | 0.485 (13) [6.4] |
| θshape , shape parameter for IIV distribution of s 0 | –0.476 (15) | – |
| Scale EFS , scaling factor for effect of weight change on insulin sensitivity | 0.0458 (9) | 75.7 (10) [19.9] |
| HbA1c | ||
| HbA1c kin , HbA1c production rate % per day | 0.0152 (3) | – |
| MTT, mean transit time (days) | 38.9 (fixed) | – |
| PPG | 0.057 (7) | 25.6 (10) [6] |
| Scale PPG | 0.967 (1) | |
| Treatment effects | ||
| EFDE , placebo, diet and exercise effect at placebo run‐in | 3.0 (16) | 21.3 (16) [12.3] |
| EFPL , placebo effect at treatment phase (Study 1 only) | 3.46 (16) | 28.9 (18) [24.9] |
| EFLOSS , rate of loss of placebo treatment effect (% /year) | 3.76 (24) | 70.4 (16) [24.1] |
| Residual errors | ||
| Weight | 0.0096 (1) | – |
| FSI | 0.265 (4) | 41.5 (6) [22.2] |
| FPG | 0.0841 (4) | 29 (11.3) [7.2] |
| HbA1c | 0.0254 (3) | 22 (10) [19.8] |
FPG, fasting plasma glucose; FSI, fasting serum insulin; HbA1c, glycosylated haemoglobin; IIV, inter‐individual variability (%); PPG, postprandial glucose; RSE, residual standard error; WGT, weight; WGT t1/2, half‐life of weight compartment
a
Normally distributed IIV (b 0 , rB , EFB , s0 , EFDE , EFPL ,DPR) were reported as absolute values