Table 2.
Primary and secondary outcomes
| Baseline | Glimepiride + placebo vs. baseline | Glimepiride + linagliptin vs. baseline | Glimepiride + linagliptin vs. glimepiride + placebo | |
|---|---|---|---|---|
| CGM | ||||
| MAGE (mmol/L) | 5.5 (4.6–6.4) | 0.3 (−0.9 to 1.5), P = 0.5616 | −0.4 (−1.6 to 0.7), P = 0.4286 | −0.7 (−1.9 to 0.3), P = 0.1540 |
| CV (%) | 27.2 (24.0–30.5) | 4.2 (−3.0 to 4.2), P = 0.0438 | 0.6 (−3.0 to 4.2), P = 0.7364 | −3.6 (−7.0 to −0.2), P = 0.0401 |
| SD (mmol/L) | 2.6 (2.3–3.0) | 0.1 (−0.3 to 0.6), P = 0.5192 | −0.4 (−0.7 to 0.1), P = 0.1000 | −0.4 (−0.8 to −0.1), P = 0.0210 |
| Mean (mmol/L) | 9.6 (8.9–10.4) | −0.9 (−1.8 to 0.0), P = 0.0548 | −1.4 (−2.2 to −0.6), P = 0.0012 | −0.5 (−1.4 to 0.4), P = 0.2341 |
| Low blood glucose index | 0.9 (0.4–1.5) | 0.7 (0.1–1.4), P = 0.0364 | 0.4 (−0.3 to 1.2), P = 0.2458 | −0.3 (−1.0 to 0.4), P = 0.3740 |
| % time in hyperglycemia (≥10.0 mmol/L) | 38.9 (29.2–48.6) | −9.8 (−21.2 to 1.7), P = 0.0894 | −15.7 (−26.0 to −5.5), P = 0.0047 | −6.0 (−16.4 to 4.5), P = 0.2470 |
| % time in near normoglycemia (4.0–9.9 mmol/L) | 60.7 (50.9–70.4) | 8.5 (−2.9 to 20.0), P = 0.1358 | 15.3 (4.7–25.8), P = 0.0068 | 6.7 (−3.9 to 17.4), P = 0.1990 |
| Biochemistry and other | ||||
| HbA1c (%) | 7.4 (7.0–7.7) | −0.4 (−0.8 to 0.1), P = 0.1165 | −0.9 (−1.3 to −0.5), P = 0.0001 | −0.5 (−0.9 to −0.2), P = 0.0048 |
| HbA1c (mmol/mol) | 57.1 (53.6–60.5) | −4.0 (−9.0 to 1.0), P = 0.1116 | −9.6 (−13.7 to −5.4), P = 0.0001 | −5.6 (−9.3 to −1.8), P = 0.0055 |
| Fasting plasma glucose (mmol/L) | 9.0 (7.9–10.0) | −1.4 (−2.5 to −0.3), P = 0.0182 | −2.1 (−3.2 to −1.0), P = 0.0008 | −0.7 (−1.4 to −0.0), P = 0.0492 |
| Mental component score (SF-36) | 53.6 (49.5–57.8) | −3.2 (−6.7 to 0.4), P = 0.0765 | 0.6 (−2.5 to 3.8), P = 0.6751 | 3.8 (−1.7 to 9.3), P = 0.1655 |
| Physical component score (SF-36) | 55.2 (52.2–58.2) | 0.8 (−0.8 to 2.4), P = 0.2891 | 2.1 (0.6–3.5), P = 0.0087 | 1.2 (−0.0 to 2.5), P = 0.0569 |
| Glimepiride dose (mg) | 1.9 (1.3–2.4) | 1.5 (0.9–2.1), P < 0.0001 | 0.8 (0.2–1.5), P = 0.0166 | −0.7 (−1.2 to −0.2), P = 0.0099 |
| Meal and bicycle test | ||||
| Plasma glucose | ||||
| AUC (mol/L × min) | 2.9 (2.5–3.4) | −0.3 (−0.5 to −0.0), P = 0.0463 | −0.6 (−0.9 to −0.3), P = 0.008 | −0.3 (−0.6 to −0.0), P = 0.0466 |
| bsAUC (mol/L × min) | 0.9 (0.6–1.2) | −0.1 (−0.3 to 0.2), P = 0.6066 | −0.2 (−0.4 to 0.0), P = 0.0975 | −0.1 (−0.4 to 0.1), P = 0.2418 |
| Excursion (mmol/L) | 7.8 (6.3–9.3) | −0.1 (−1.3 to 1.1), P = 0.8478 | −0.6 (−1.8 to 0.7), P = 0.3396 | −0.5 (−1.9 to 1.0), P = 0.4976 |
| Peak (mmol/L) | 15.3 (13.2–17.5) | −0.9 (−2.2 to 0.4), P = 0.1482 | −2.3 (−3.8 to −0.8), P = 0.0042 | −1.4 (−3.2 to 0.3), P = 0.1090 |
| C-peptide | ||||
| AUC (nmol/L × min) | 226 (174–278) | −7 (−23 to 93), P = 0.3847 | 2 (−15 to 19), P = 0.7813 | 9 (−3.5 to 22), P = 0.1453 |
| bsAUC (nmol/L × min) | 142 (107–176) | −21 (−39 to −4), P = 0.0174 | −5 (−25 to 15), P = 0.6073 | 17 (−3 to 36), P = 0.0940 |
| C-peptide–to–glucose ratio | ||||
| AUC (pmol/L × mmol−1 × 10−3 × min) | 20 (14–26) | 2 (−2 to 6), P = 0.2588 | 7 (3–12), P = 0.0018 | 5 (2–8), P = 0.0008 |
| bsAUC (pmol/L × mmol−1 × 10−3 × min) | 9 (5–13) | 1 (−3 to 2), P = 0.5979 | 4 (−2 to 9), P = 0.1603 | 4 (1–8), P = 0.0261 |
| Glucagon | ||||
| Fasting levels (pmol/L) | 7.4 (5.6–9.1) | 0.1 (−1.3 to 1.6), P = 0.8473 | −0.7 (−2.4 to 1.0), P = 0.4108 | −0.8 (−2.3 to 0.7), P = 0.2661 |
| AUC (nmol/L × min) | 3.1 (2.6–3.7) | −0.0 (−0.4 to 0.4), P = 0.8962 | −0.2 (−0.5 to 0.1), P = 0.1535 | −0.2 (−0.5 to 0.1), P = 0.2458 |
| bsAUC (nmol/L × min) | 1.3 (0.9–1.7) | −0.0 (−0.4 to 0.4), P = 0.9280 | 0.0 (−0.4 to 0.4), P = 0.9731 | 0.0 (−0.2 to 0.3), P = 0.8538 |
| Acetaminophen | ||||
| AUC (µmol/L × min) | 15.4 (14.1–16.8) | 0.0 (−0.7 to 0.8), P = 0.9159 | −0.6 (−1.4 to 0.1), P = 0.0879 | −0.7 (−1.4 to −0.0), P = 0.0479 |
| Time to peak (min) | 122 (110–133) | −3 (−18 to 13), P = 0.7337 | 11 (−2 to 25), P = 0.0936 | 14 (2–26), P = 0.0238 |
| Peak (µmol/L) | 0.10 (0.09–0.11) | 0.01 (−0.05 to 0.02), P = 0.2448 | 0.00 (−0.01 to 0.01), P = 0.8526 | −0.01 (−0.01 to −0.00), P = 0.0439 |
Data are mean (95% CI). SF-36, 36-Item Short Form Health Survey, version 2.