Double-blind Treatment Period: 24 weeks

Group A: placebo daily with morning meal

Group B: DAPA 1 mg daily with morning meal

Group C: DAPA 2.5 mg daily with morning meal

Group D: DAPA 5 mg daily with morning meal

Safety-assessment Follow-up Period:

4 weeks

(−0.91, −0.45)

(−1.02, −0.37)

DAPA 2.5 mg (N = 74)

8.1 ± 1.07

−0.72

−0.74^*

(−0.95, −0.49)

(−1.07, −0.41)

DAPA 5 mg

(N = 68)

7.9 ± 1.03

−0.82

−0.84^*

(−1.06, −0.58)

(−1.17, −0.50)

^*p < 0.0001 vs. PBO

FPG (mg/dL) at 24 Weeks

Baseline Mean ± SD

Adjusted Mean Change

(95% CI)

Difference vs. PBO

(95% CI)

PBO (N = 68)

161.6 ± 57.5

4.1

-

(−4.1, 12.4)

DAPA 1 mg

(N = 72)

155.5 ± 48.3

−11

−15.1^*

(−19.1, −3.1)

(−26.7, −3.6)

DAPA 2.5 mg (N = 74)

159.8 ± 51.5

−21.6

−25.8^**

(−29.5, −13.7)

(−37.1, −14.2)

DAPA 5 mg

(N = 68)

157.1 ± 41.6

−28.5

−32.6^**

(−36.8, −20.2)

(−44.3, −20.7)

^*p = 0.0103 vs. PBO

^**p < 0.0001 vs. PBO

Body Weight (kg) at 24 Weeks

Baseline Mean ± SD

Adjusted Mean Change

(95% CI)

Difference vs. PBO

(95% CI)

PBO (N = 68)

90.0 ± 17.98

−0.96

-

(−1.74, −0.19)

DAPA 1 mg

(N = 72)

88.2 ± 18.49

−2.69

−1.73^*

(−3.44, −1.94)

(−2.81, −0.65)

DAPA 2.5 mg (N = 74)

84.3 ± 18.18

−2.64

−1.68^**

(−3.38, −1.90)

(−2.76, −0.60)

DAPA 5 mg

(N = 68)

85.4 ± 19.43

−2.69

−1.73^***

(−3.47, −1.91)

(−2.83, −0.63)

^*p = 0.0018 vs. PBO

^**p = 0.0024 vs. PBO

^***p = 0.0022 vs. PBO

Henry

(2012)

Two Randomized

Double-blind

Active-

controlled

1236

T2DM

(573M; 663F)

Single-blind Placebo Lead-in Period:

1 week

Double-blind Treatment Period: 24 weeks

Study I:

Group A: MET XR + placebo combination with evening meal

HbA1C (%) at 24 Weeks - Study I

Baseline Mean ± SD

Adjusted Mean Change

(95% CI)

Difference vs. Monotherapy

(95% CI)

MET + PBO

(N = 201)

9.2 ± 1.3

−1.35

(−1.53, −1.18)

-

DAPA 5 mg + MET

(N = 194)

9.2 ± 1.3

−2.05

(−2.23, −1.88)

−0.86^*

(−1.11, −0.62)

−0.70^**

(−0.94, −0.45)