Table 2

Efficacy parameters, adverse events, vital signs, and laboratory parameters

Dapagliflozin dose
PlaceboMetformin
2.5 mg5 mg10 mg20 mg50 mg
Efficacy parameters
    A1C (%)*−0.71 ± 0.09−0.72 ± 0.09−0.85 ± 0.11−0.55 ± 0.09−0.90 ± 0.10−0.18 ± 0.10−0.73 ± 0.10
        P value vs. placebo<0.001<0.001<0.0010.007<0.001
    FPG (mg/dl)*−16 ± 3−19 ± 3−21 ± 4−24 ± 3−31 ± 3−6 ± 3−18 ± 3
        P value vs. placebo0.030.0050.002<0.001<0.001
    PPG AUC (mg · min−1 · dl−1*−9,382−8,478−10,149−7,053−10,093−3182−5891
        95% CI−11,420 to −7,344−10,200 to −6,756−12,215 to −8,082−8,913 to −5,194−12,024 to −8,162−5,086 to −1,277−7,775 to −4,008
    Proportion with A1C <7.0%§26 (46)23 (40)23 (52)26 (46)31 (59)16 (32)29 (54)
        P value vs. placebo0.170.430.060.170.01
    24-h urinary glucose/creatinine (g/g)*32 ± 349 ± 351 ± 365 ± 360 ± 3−0.2 ± 3−1.4 ± 3
        P value vs. placebo<0.001<0.001<0.001<0.001<0.001
    Body weight reduction (%)*−2.7−2.5−2.7−3.4−3.4−1.2−1.7
        95% CI−3.4 to −1.9−3.3 to −1.8−3.5 to −1.8−4.1 to −2.6−4.1 to −2.6−2.0 to −0.4−2.4 to −0.9
    Total 24-h urinary glucose (g/24 h)§52 ± 3964 ± 3468 ± 3885 ± 4382 ± 386 ± 176 ± 21
Adverse events (double-blind period)
    Total subjects with an adverse event35 (59)35 (60)32 (68)40 (68)35 (63)29 (54)38 (68)
    Serious adverse events1 (2)01 (2)1 (2)1 (2)01 (2)
    Discontinuation for adverse events1 (2)03 (6)2 (3)2 (4)1 (2)1 (2)
Most common adverse events (≥10% in any group) by MedDRA preferred term
    Urinary tract infection3 (5)5 (9)5 (11)4 (7)4 (7)3 (6)4 (7)
    Nausea3 (5)4 (7)3 (6)2 (3)3 (5)3 (6)6 (11)
    Headache4 (7)3 (5)2 (4)3 (5)1 (2)6 (11)2 (4)
    Diarrhea1 (2)1 (2)1 (2)4 (7)1 (2)4 (7)7 (13)
Events by special interest category
    Hypoglycemic events4 (7)6 (10)3 (6)4 (7)4 (7)2 (4)5 (9)
    Infections of the urinary tract3 (5)5 (9)5 (11)7 (12)5 (9)3 (6)5 (9)
    Genital infections2 (3)1 (2)1 (2)4 (7)4 (7)0 (0)1 (2)
    Urinary tract or genital infection4 (6.8)6 (10.3)5 (10.6)10 (16.9)9 (16.1)3 (5.6)6 (10.7)
    Hypotensive events#0 (0)0 (0)0 (0)0 (0)1 (2)1 (2)2 (4)
Vital signs**
    sBP (mmHg)−3.1 ± 10.7−2.9 ± 12.7−6.4 ± 11.4−4.3 ± 12.3−2.6 ± 13.12.4 ± 11.1−0.4 ± 12.4
        P value vs. placebo0.020.040.0010.0080.056
    dBP (mmHg)0.8 ± 6.4−0.3 ± 7.0−2.6 ± 7.7−0.5 ± 7.10.1 ± 8.00.3 ± 5.7−0.6 ± 8.0
        P value vs. placebo0.670.660.070.560.89
    Heart rate (beats/min)−1.4 ± 8.0−1.0 ± 8.9−0.03 ± 8.91.9 ± 11.20.1 ± 7.1−2.3 ± 7.81.1 ± 9.6
        P value vs. placebo0.580.450.210.040.12
    Urine output (ml/24h)**106.6 ± 606.9340.0 ± 551.3374.5 ± 741.6374.9 ± 723.1470.3 ± 797.5−111.5 ± 655.4−95.8 ± 75.4
        P value vs. placebo0.09<0.0010.002<0.001<0.001
Laboratory parameters**
    Creatinine (mg/dl)−0.01 ± 0.10−0.00 ± 0.10−0.02 ± 0.08−0.01 ± 0.090.02 ± 0.11−0.00 ± 0.10−0.02 ± 0.12
        P value vs. placebo0.730.980.340.900.22
    BUN (mg/dl)1.07 ± 3.960.71 ± 3.072.03 ± 3.720.87 ± 3.371.32 ± 3.61−0.96 ± 2.81−0.18 ± 2.67
        P value vs. placebo0.0040.006<0.0010.0050.001
    Sodium (mEq/l)0.28 ± 2.900.56 ± 2.62−0.15 ± 2.060.56 ± 2.280.50 ± 3.510.93 ± 2.83−0.06 ± 2.35
        P value vs. placebo0.260.500.050.460.51
    Potassium (mEq/l)−0.04 ± 0.340.02 ± 0.360.00 ± 0.32−0.03 ± 0.290.00 ± 0.45−0.01 ± 0.44−0.04 ± 0.53
        P value vs. placebo0.760.710.880.840.88
    Calcium (mg/dl)−0.11 ± 0.35−0.04 ± 0.47−0.12 ± 0.44−0.11 ± 0.370.01 ± 0.48−0.10 ± 0.48−0.09 ± 0.55
        P value vs. placebo0.900.500.860.950.25
    Magnesium (mEq/l)0.07 ± 0.140.10 ± 0.130.12 ± 0.190.14 ± 0.120.18 ± 0.160.04 ± 0.16−0.03 ± 0.16
        P value vs. placebo0.300.040.030.001<0.001
    Phosphate (mg/dl)−0.01 ± 0.500.07 ± 0.500.12 ± 0.580.20 ± 0.430.24 ± 0.600.08 ± 0.47−0.08 ± 0.54
        P value vs. placebo0.350.92 SD0.730.170.15
    Uric acid (mg/dl)−1.03 ± 0.81−1.12 ± 0.84−0.98 ± 0.66−1.13 ± 0.78−1.14 ± 1.15−0.16 ± 0.750.18 ± 0.53
        P value vs. placebo<0.001<0.001<0.001<0.001<0.001
    Hematocrit (%)1.51 ± 2.122.03 ± 2.361.95 ± 2.192.57 ± 2.442.86 ± 2.75−0.08 ± 2.16−1.12 ± 2.62
        P value vs. placebo0.001<0.001<0.001<0.001<0.001
  • Data are means ± SD or n (%).

  • *Change from baseline at week 12, LOCF. Missing data imputed by LOCF ranged from 5.2 to 13.6% (A1C), 11.5 to 26.0% (FPG), 5.2 to 13.6% (proportion with A1C <7.0%), and 2.0 to 8.2% (24-h urinary glucose/creatinine).

  • †A1C, FPG, PPG, and 24-h urinary glucose/creatinine represent adjusted mean changes.

  • ‡Between-group comparisons significant at α = 0.012, applying Dunnett's adjustment.

  • §Absolute week 12 value.

  • ‖“Infections of the urinary tract” were events of urinary tract infection, cystitis, Escherichia urinary tract infection, urinary tract infection fungal, and fungal infection (verbatim investigator term “yeast infection [in urine]”).

  • ¶“Genital infections” were events of vulvovaginal mycotic infection, vaginal infection, genital herpes, genital infection fungal, penile infection, vaginitis bacterial, and vulvitis.

  • #“Hypotensive events” were events of hypotension, orthostatic hypotension, and syncope.

  • **Change from baseline at week 12.