Rosenstock

(2013)

Randomized

Double-blind

Placebo-

controlled

495 T2DM

(250M; 245F)

Screening Period: over 1 week

Oral (non-metformin) AHA Washout Period (if applicable): 4 weeks

Placebo Run-in Period: 2 weeks

Double-blind

Treatment Period: 12 weeks

Group A:

placebo once daily + MET

Group B: EMPA 5 mg once daily + MET

Group C: EMPA10 mg once daily + MET

Group D: EMPA 25 mg once daily + MET

Group E: Open-label SITA100mg once daily + MET

Follow-up Visit:

1 week after last treatment

HbA1C (%) at 12 Weeks

Baseline Mean ± SD

Adjusted Mean Change

Difference vs. PBO

(95% CI)

(95% CI)

PBO

8.0 ± 0.7

0.15

-

(N = 71)

(−0.00, 0.30)

EMPA 1 mg

7.8 ± 0.7

−0.09

-

(N = 71)

(−0.24, 0.07)

EMPA 5 mg

8.0 ± 0.7

−0.23*

-

−71

(−0.39, −0.08)

EMPA 10 mg

7.9 ± 0.7

−0.56**

-

(N = 71)

(−0.71, −0.41)

EMPA 25 mg

8.1 ± 0.8

−0.55**

-

(N = 70)

(−0.70, −0.40)

EMPA 50 mg

7.9 ± 0.7

−0.49**

-

(N = 70)

(−0.64, −0.33)

SITA

8.1 ± 0.9

−0.45**

-

(N = 71)

(−0.65, −0.25)

*p ≤ 0.001 vs. PBO

**p ≤ 0.0001 vs. PBO

FPG (mg/dL) at 12 Weeks

Baseline Mean ± SD

Adjusted Mean Change

Difference vs. PBO

(95% CI)

(95% CI)

PBO

174 ± 40

5

-

(N = 71)

(−2, 12)

EMPA 1 mg

173 ± 40

−2

-

(N = 71)

(−9, 5)

EMPA 5 mg

180 ± 43

−16*

-

−71

(−23, −9)

EMPA 10 mg

173 ± 36

−22*

-

(N = 71)

(−29, −16)

EMPA 25 mg

180 ± 48

−27*

-

(N = 70)

(−34, −20)

EMPA 50 mg

175 ± 35

−28*

-

(N = 70)

(−35, −21)

SITA

178 ± 44

−13**

-

(N = 71)

(−22, −3)

*p ≤ 0.0001 vs. PBO

**p ≤ 0.01 vs. PBO

Body Weight (kg) at 12 Weeks

Baseline Mean ± SD

Adjusted Mean Change

Difference vs. PBO

(95% CI)

(95% CI)

PBO

87.7 ± 15.7

−1.2

-