| Bode (2013) | Randomized Double-blind Placebo- controlled | 714 T2DM with (396M; 318F) | Single-blind, Placebo Run-in Period: 2 weeks
Double-blind Core Treatment Period: 26 weeks
Group A: placebo daily before first meal of day
Group B: CANA 100 mg daily before first meal of day
Group C: CANA 300 mg daily before first meal of day
Double-blind Extension Period: 78 weeks | HbA1C (%) at 26 Weeks | ||||||||||||
| Baseline Mean ± SD | Adjusted Mean Change | Difference vs. PBO | ||||||||||||||
| PBO (N = 237) | 7.8 ± 0.8 | −0.03 | - | |||||||||||||
| CANA 100 mg (N = 241) | 7.8 ± 0.8 | −0.6 | −0.57* | |||||||||||||
| CANA 300 mg (N = 236) | 7.7 ± 0.8 | −0.73 | −0.70* | |||||||||||||
| *p < 0.001 vs. PBO | ||||||||||||||||
| FPG (mg/dL) at 26 Weeks | ||||||||||||||||
| Baseline Mean ± SD | Adjusted Mean Change | Difference vs. PBO | ||||||||||||||
| PBO (N = 237) | 156.8 ± 38.9 | 7.4 | - | |||||||||||||
| CANA 100 mg (N = 241) | 160.4 ± 38.7 | −18.1 | −25.5* | |||||||||||||
| CANA 300 mg (N = 236) | 153.2 ± 36.6 | −20.3 | −27.7* | |||||||||||||
| *p < 0.001 vs. PBO | ||||||||||||||||
| Body Weight (kg) at 26 Weeks | ||||||||||||||||
| Baseline Mean ± SD | Adjusted Mean Percent Change | Difference vs. PBO | ||||||||||||||
| PBO (N = 237) | 91.1 ± 17.5 | 0.1 | - | |||||||||||||
| CANA 100 mg (N = 241) | 88.4 ± 15.6 | −2.4 | −2.3* | |||||||||||||
| CANA 300 mg (N = 236) | 88.8 ± 17.1 | −3.1 | −3.0* | |||||||||||||
| *p < 0.001 vs. PBO | ||||||||||||||||
| Cefalu (2013) | Randomized Double-blind Active- controlled Non- inferiority | 1450 T2DM (756M; 694F) | Single-Blind Run-in Period: 2 weeks
Study Phase: 52 weeks
All groups on stable daily metformin dose for at least 10 weeks plus
Group A: GLIM 1 - 6 mg or 1 - 8 mg daily (based on maximum approved dose in country of investigational site)
Group B: CANA 100 mg daily
Group C: CANA 300 mg daily
Double-blind Extension Period: 52 weeks | HbA1C (%) at 52 Weeks | ||||||||||||
| Baseline Mean ± SD | LS Mean Change ± SE | Difference vs. GLIM (95% CI) | ||||||||||||||
| GLIM (N = 482) | 7.8 ± 0.8 | −0.81 ± 0.04 | - | |||||||||||||
| CANA 100 mg (N = 483) | 7.8 ± 0.8 | −0.82 ± 0.04 | −0.01 (−0.11, 0.09) | |||||||||||||
| CANA 300 mg (N = 485) | 7.8 ± 0.8 | −0.93 ± 0.04 | −0.12 (−0.22, −0.02) | |||||||||||||
| FPG (mg/dL) at 52 Weeks | ||||||||||||||||
| Baseline Mean ± SD | LS Mean Change | Difference vs. GLIM (95% CI) | ||||||||||||||
| GLIM (N = 482) | 165.8 ± 37.8 | −18.4 | - | |||||||||||||
| CANA 100 mg (N = 483) | 165.8 ± 37.8 | −24.3 | −5.9 (−10.8, −1.8) | |||||||||||||
| CANA 300 mg (N = 485) | 164.0 ± 36.0 | −27.4 | −9.2 (−12.6, −5.4) | |||||||||||||