TABLE 3.
Summary of key pharmacodynamic biomarkers at baseline and at 8 weeks a following twice‐daily oral dosing of danuglipron
| Biomarker | Placebo (N = 9) | Danuglipron dose | ||
|---|---|---|---|---|
| 40 mg BID (N = 10) | 80 mg BID (N = 9) | 120 mg BID (N = 9) | ||
| MDG (mg/dl) | ||||
| Absolute mean (SD) at baseline | 218.8 (59.8) | 223.4 (50.5) | 240.6 (52.3) | 200.0 (56.3) |
| Absolute mean (SD) at Day 56 | 195.5 (42.0) | 138.8 (19.2) | 152.7 (49.7) | 120.4 (24.0) |
| Absolute mean (SD) CFB | −8.34 (10.34) | −87.60 (44.27) | −95.55 (28.45) | −67.64 (48.83) |
| LS‐mean (90% CI) CFB b | −13.98 (−28.29, 0.32) | −81.87 (−97.15, −66.59) | −78.80 (−96.05, −61.55) | −81.27 (−97.07, −65.48) |
| LS‐mean (90% CI) placebo‐adjusted CFB b | – | −67.89 (−88.98, −46.79) | −64.82 (−87.66, −41.98) | −67.29 (−88.22, −46.36) |
| FPG (mg/dl) | ||||
| Absolute mean (SD) at baseline | 182.9 (36.3) | 173.3 (29.7) | 175.7 (32.7) | 163.7 (47.5) |
| Absolute mean (SD) at Day 57 | 163.6 (29.0) | 137.3 (18.2) | 130.5 (22.3) | 112.7 (18.7) |
| Absolute mean (SD) CFB | −11.88 (6.81) | −39.71 (14.74) | −46.17 (24.63) | −41.86 (36.22) |
| LS‐mean (90% CI) CFB c | −9.26 (−18.16, −0.37) | −36.51 (−45.60, −27.42) | −46.04 (−55.47, −36.62) | −50.14 (−59.35, −40.92) |
| LS‐mean (90% CI) placebo‐adjusted CFB c | – | −27.25 (−39.95, −14.55) | −36.78 (−49.72, −23.85) | −40.87 (−53.77, −27.98) |
| HbA1c (%) | ||||
| Absolute mean (SD) at baseline | 8.3 (1.2) | 8.2 (1.1) | 8.6 (1.0) | 8.4 (1.2) |
| Absolute mean (SD) at Day 57 | 7.8 (0.9) | 6.8 (0.7) | 7.3 (1.5) | 6.6 (0.4) |
| Absolute mean (SD) CFB | −0.18 (0.21) | −1.29 (0.58) | −1.40 (0.89) | −1.60 (1.15) |
| LS‐mean (90% CI) CFB c | −0.14 (−0.56, 0.28) | −1.34 (−1.76, −0.92) | −1.00 (−1.42, −0.57) | −1.55 (−1.97, −1.13) |
| LS‐mean (90% CI) placebo‐adjusted CFB c | – | −1.20 (−1.80, −0.61) | −0.86 (−1.46, −0.26) | −1.41 (−2.01, −0.82) |
| Body weight (kg) | ||||
| Absolute mean (SD) at baseline | 73.3 (9.9) | 79.7 (13.6) | 79.6 (10.0) | 81.5 (10.4) |
| Absolute mean (SD) at Day 57 | 74.1 (8.8) | 74.4 (12.1) | 78.4 (8.6) | 77.0 (9.3) |
| Absolute mean (SD) CFB | −0.93 (0.94) | −2.47 (1.37) | −3.68 (2.26) | −3.26 (2.95) |
| LS‐mean (90% CI) CFB c | −1.21 (−2.36, −0.05) | −2.61 (−3.77, −1.45) | −3.08 (−4.30, −1.86) | −2.87 (−3.98, −1.75) |
| LS‐mean (90% CI) placebo‐adjusted CFB c | – | −1.40 (−3.03, 0.23) | −1.87 (−3.58, −0.17) | −1.66 (−3.28, −0.04) |
Note: data are absolute mean (SD) or LS‐mean (90% CI) as indicated. Baseline for MDG was defined as glucose AUC24/24 h on Day −1. Baselines for FPG, HbA1c and body weight were defined as the measurement at Day −1, 0 h. For calculation of MDG, for glucose at 24 h on Day –1 and 24 h on Day 56, glucose at 0 h on Day –1 and 0 h on Day 57 were used from the same participant, respectively.
Abbreviations: ANCOVA, analysis of covariance; BID, twice daily; CFB, change from baseline; CI, confidence interval; FPG, fasting plasma glucose; HbA1c, glycated haemoglobin; LS, least squares; MDG, mean daily glucose; MMRM, mixed model repeated measures; SD, standard deviation.
Day 56 for MDG; Day 57 for FPG, HbA1c and body weight.
From an ANCOVA model that included the change from baseline in MDG on Day 56 as the dependent variable, treatment as a fixed effect and baseline MDG as a covariate.
From an MMRM analysis that included treatment, baseline value, day, the baseline‐by‐day interaction and the day‐by‐treatment interaction, with day fitted as a repeated effect and participant as a random effect.