MET + PBO

(N = 201)

85.6 ± 20.0

−1.29

(−1.76 to −0.82)

-

DAPA 5 mg + MET

(N = 194)

84.1 ± 19.5

−2.66

(−3.14, −2.19)

−0.05^*

(−0.72, 0.61)

−1.37^**

(−2.04, −0.71)

DAPA 5 mg + PBO

(N = 203)

86.2 ± 21.1

−2.61

(−3.07, −2.15)

-

Body Weight (kg) at 24 Weeks - Study II

Baseline Mean ± SD

Adjusted Mean Change

(95% CI)

Difference vs. Monotherapy

(95% CI)

MET + PBO

(N = 208)

87.2 ± 19.4

−1.36

(−1.83, −0.89)

-

DAPA 10 mg + MET

(N = 211)

88.4 ± 19.7

−3.33

(−3.80, −2.86)

−1.97^***

(−2.64, −1.30)

DAPA 10 mg + PBO

(N = 219)

88.5 ± 19.3

−2.73

(−3.19, −2.27)

−1.37^****

(−2.03, −0.71)

^*p = 0.8769 vs. DAPA + PBO

^**p < 0.0001 vs. MET + PBO

^***p < 0.0001 vs. MET + PBO (after sequential testing procedure at α = 0.05)

^****p < 0.0001 vs. DAPA vs. MET (after sequential testing procedure at α = 0.05)

Rosenstock

(2012)

Randomized

Double-blind

Parallel-group

Placebo- Controlled

420

T2DM

(208M; 212F)

PIO dose-optimization period for treatment-naïve patients or those receiving MET, SU, or low dose TZD: 10 weeks

Single-blind, Lead-in Period: 2 weeks

Double-blind Treatment Period:

24 weeks

Group A: placebo + PIO 30 mg or 45 mg

Group B: DAPA 5 mg + PIO 30 mg or 45 mg

Group C: DAPA 10 mg + PIO 30 mg or 45 mg

Extension Period:

24 weeks

HbA1C (%) at 24 Weeks

Baseline Mean ± SD

Adjusted Mean Change ± SE

Difference vs. PBO

PBO

8.34 ± 1.00

−0.42 ± 0.08

-

(N = 139)

DAPA 5 mg

8.40 ± 1.03

−0.82 ± 0.08^*

-

(N = 141)

DAPA 10 mg

8.37 ± 0.96

−0.97 ± 0.08^**

-

(N = 140)

^*p = 0.0007 vs. PBO

^**p < 0.0001 vs. PBO

FPG (mg/dL) at 24 Weeks

Baseline Mean ± SD

Adjusted Mean Change ± SE

Difference vs. PBO

PBO

160.7 ± 47.0

−5.5 ± 2.9

-

(N = 139)

DAPA 5 mg

168.6 ± 52.1

−24.9 ± 2.9^*

-

(N = 141)

DAPA 10 mg

164.9 ± 46.3

−29.6 ± 2.9^*

-

(N = 140)

^*p < 0.0001 vs. PBO

Body Weight (kg) at 24 Weeks