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)