Stenlöf

(2013)

Randomized Double-blind

Placebo- controlled

584 T2DM

(258M; 326F)

AHA Washout/Diet and Exercise Period: 8 weeks

Single-blind Placebo Run-in period: 2 weeks

Double-blind,

Placebo-controlled Treatment Period: 26 weeks

Group A:

placebo daily

Group B:

CANA 100 mg daily

Group C:

CANA 300 mg daily

Double-blind

Extension Period: 26 weeks

HbA1C (%) at 26 Weeks

Baseline Mean ± SD

LS Mean Percent Change

Difference vs. PBO

(95% CI)

PBO

(N = 192)

8.0 ± 1.0

0.14

-

CANA 100 mg (N = 195)

8.1 ± 1.0

−0.77

−0.91^*

(−1.1, −0.7)

CANA 300 mg (N = 197)

8.0 ± 1.0

−1.03

−1.16^*

(−1.3, −1.0)

^*p < 0.001 vs. PBO

FPG (mg/dL) at 26 Weeks

Baseline Mean ± SD

LS Mean Change

Difference vs. PBO

(95% CI)

PBO

(N = 192)

167.6 ± 37.8

9

-

CANA 100 mg (N = 195)

173.0 ± 43.2

−27

−36.0^*

(−41.4, −28.8)

CANA 300 mg (N = 197)

173.0 ± 43.2

−34.2

−43.2^*

(−50.5, −36.0)

^*p < 0.001 vs. PBO

Body Weight (kg) at 26 Weeks

Baseline Mean ± SD

LS Mean Percent Change

Difference vs. PBO

(95% CI)

PBO

(N = 192)

87.6 ± 19.5

−0.6

-

CANA 100 mg (N = 195)

85.8 ± 21.4

−2.8

−2.2^*

(−2.9, −1.6)

CANA 300 mg (N = 197)

86.9 ± 20.5

−3.9

−3.3^*

(−4.0, −2.6)

^*p < 0.001 vs. PBO

Wilding

(2013)

Randomized

Double-blind

Placebo-

controlled

469 T2DM

(239M; 230F)

MET and SU Maximum Effective Dose Pretreatment Period: up to 12 weeks (dose titration up to 4 weeks; stable dose for 8 weeks)

Single-blind, Placebo Run-in Period: 2 weeks

Double-blind Treatment Period: 26 weeks

Group A: placebo daily before first meal

Group B: CANA 100 mg daily before first meal

Group C: CANA 300 mg daily before first meal

Double-blind Extension Period: 26 weeks

HbA1C (%) at 26 Weeks

Baseline Mean ± SD

LS Mean Change

Difference vs. PBO

(95% CI)

PBO

(N = 156)

8.1 ± 0.9

−0.13

-

CANA 100 mg (N = 157)

8.1 ± 0.9

−0.85

−0.71^*

(−0.90, −0.52)

CANA 300 mg (N = 156)

8.1 ± 0.9

−1.06

−0.92^*

(−1.11, −0.73)

^*p < 0.001 vs. PBO

FPG (mg/dL) at 26 Weeks

Baseline Mean ± SD

LS Mean Change

Difference vs. PBO

(95% CI)

PBO

(N = 156)

169.4 ± 39.6

3.6

-

CANA 100 mg (N = 157)

173.0 ± 41.4

−18

−21.6^*

(−30.6, −12.6)

CANA 300 mg (N = 156)

167.6 ± 37.8

−30.6

−34.2^*

(−43.2, −25.2)