TABLE 2.
Effects of imeglimin versus placebo on primary and secondary efficacy end points
| Imeglimin | Placebo | |
|---|---|---|
| 180‐min AUC Glucose (mmol/L·min), n | 29 | 27 |
| Baseline, mean (SD) | 3181.0 (679.0) | 3005.6 (552.0) |
| Change from baseline, LSM | −720.7 | −291.0 |
| Difference vs. placebo, LSM (95% CI) | −429.6 (−678.0, −181.3) | |
| p = .001 | ||
| 180‐min iAUC Glucose (mmol/L·min), n | 29 | 27 |
| Baseline, mean (SD) | 1291.6 (381.2) | 1315.7 (379.2) |
| Change from baseline, LSM | −369.6 | −149.3 |
| Difference vs. placebo, LSM (95% CI) | −220.3 (−399.6, −41.0) | |
| p = .017 | ||
| HbA1c (%), n | 29 | 28 |
| Baseline, mean (SD) | 8.12 (0.56) | 8.14 (0.61) |
| Change from baseline, LSM | −0.46 | 0.17 |
| Difference vs. placebo, LSM (95% CI) | −0.62 (−1.11, −0.14) | |
| p = .013 | ||
| Pre‐dose Fasting Plasma Glucose (mmol/L), n | 29 | 28 |
| Baseline, mean (SD) | 11.33 (2.53) | 10.25 (1.92) |
| Change from baseline, LSM | −1.59 | −0.69 |
| Difference vs. placebo, LSM (95% CI) | −0.91 (−1.97, −0.15) | |
| p = .092 | ||
| Post‐dose Fasting Plasma Glucose (mmol/L), n | 29 | 26 |
| Baseline, mean (SD) | 10.51 (2.74) | 9.45 (2.02) |
| Change from baseline, LSM | −2.01 | −0.80 |
| Difference vs. placebo, LSM (95% CI) | −1.22 (−2.25, −0.18) | |
| p = .022 | ||
| Pre‐dose Fasting Insulin (pmol/L), n | 29 | 27 |
| Baseline, mean (SD) | 11.83 (6.80) | 19.16 (17.32) |
| Change from baseline, LSM | −2.51 | −1.84 |
| Difference vs. placebo, LSM (95% CI) | −0.67 (−3.58, 2.24) | |
| p = .646 | ||
| Post‐dose Fasting Glucagon (pmol/L), n | 19 | 18 |
| Baseline, mean (SD) | 95.6 (30.79) | 106.8 (37.92) |
| Change from baseline, LSM | −2.0 | −4.5 |
| Difference vs. placebo, LSM (95% CI) | 2.5 (−12.3, 17.3) | |
| p = .730 | ||
| 180‐min AUC Insulin (pmol/L·min), n | 29 | 26 |
| Baseline, mean (SD) | 5427.3 (2555.0) | 6888.2 (4262.7) |
| Change from baseline, LSM | 686.6 | 307.6 |
| Difference vs. placebo, LSM (95% CI) | 379.1 (−1203.4, 1961.5) | |
| p = .633 | ||
| 180‐min AUC C‐peptide (nmol/L·min), n | 28 | 27 |
| Baseline, mean (SD) | 369.0 (121.7) | 379.0 (142.0) |
| Change from baseline, LSM | 44.5 | −0.0 |
| Difference vs. placebo, LSM (95% CI) | 44.5 (−0.4, 89.5) | |
| p = .052 | ||
| Stumvoll index, n | 29 | 27 |
| Baseline, mean (SD) | 0.0439 (0.0159) | 0.0441 (0.0160) |
| Change from baseline, LSM | 0.0182 | 0.0049 |
| Difference vs. placebo, LSM (95% CI) | 0.0133 (0.0058, 0.0208) | |
| p = .001 | ||
| Matsuda index, n | 28 | 23 |
| Baseline, mean (SD) | 2.84 (2.04) | 2.82 (5.01) |
| Change from baseline, LSM | 1.54 | −0.02 |
| Difference vs. placebo, LSM (95% CI) | 1.55 (−1.06, 4.17) | |
| p = .237 | ||
| OGIS index (2‐h equation ‐ ml/min/m2), n | 27 | 23 |
| Baseline, mean (SD) | 267.42 (49.121) | 281.62 (45.527) |
| Change from baseline, LSM | 25.96 | 18.89 |
| Difference vs. placebo, LSM (95% CI) | 7.08 (−21.16, 35.32) | |
| p = .616 | ||
| QUICKI, n | 29 | 27 |
| Baseline, mean (SD) | 0.218 (0.034) | 0.208 (0.037) |
| Change from baseline, LSM | 0.014 | 0.002 |
| Difference vs. placebo, LSM (95% CI) | 0.012 (−0.008, −0.031) | |
| p = .244 | ||
| Insulinogenic index (pmol/mmol), n | 28 | 23 |
| Baseline, mean (SD) | 2.39 (1.96) | 2.52 (2.35) |
| Change from baseline, LSM | 2.55 | 0.76 |
| Difference vs. placebo, LSM (95% CI) | 1.79 (0.24, 3.34) | |
| p = .025 | ||
| AUC0‐180 min C‐peptide / AUC0‐180 min glucose (nmol/mmol), n | 28 | 27 |
| Baseline, mean (SD) | 0.122 (0.048) | 0.137 (0.083) |
| Change from baseline, LSM | 0.054 | 0.012 |
| Difference vs. placebo, LSM (95% CI) | 0.041 (0.023, 0.060) | |
| p < .001 | ||
| Rate sensitivity (pmol/m2/mmol/L), n | 29 | 27 |
| Baseline, mean (SD) | 226.64 (209.62) | 207.35 (210.37) |
| Change from baseline, LSM | 211.61 | 28.36 |
| Difference vs. placebo, LSM (95% CI) | 183.25 (−1.17, 367.67) | |
| p = .051 | ||
| Insulin Secretion at 10 mmol/L Glucose from the Dose–Response (pmol/min/m2), n | 29 | 27 |
| Baseline, mean (SD) | 132.88 (70.24) | 178.10 (140.89) |
| Change from baseline, LSM | 65.79 | 11.31 |
| Difference vs. placebo, LSM (95% CI) | 54.48 (14.68, 94.28) | |
| p = .008 | ||
| Glucose sensitivity (pmol/min/m2/mmol/L), n | 29 | 27 |
| Baseline, mean (SD) | 20.41 (9.45) | 24.13 (25.38) |
| Change from baseline, LSM | 14.54 | 2.29 |
| Difference vs. placebo, LSM (95% CI) | 12.25 (4.20, 20.30) | |
| p = .004 |
Abbreviations: AUC, area under the curve; CI, confidence interval; HbA1c, glycated haemoglobin; HOMA‐IR, homeostatic model assessment for insulin resistance; iAUC, incremental area under the curve; LSM, least square mean; SD, standard deviation.