Supplementary Materials

Efficacy and safety of ipragliflozin as an add-on to a sulfonylurea in Japanese patients with inadequately controlled type 2 diabetes: Results of the randomized, placebo-controlled, double-blind, Phase III EMIT study

Atsunori Kashiwagi · Noriko Akiyama · Takanori Shiga · Kenichi Kazuta · Atsushi Utsuno · Satoshi Yoshida · Eiji Ueyama

Supplementary Tables 1–3

Supplementary Figure 1

Table 1 Changes in efficacy outcomes from baseline to Week 24 in patients using a low sulfonylurea dose a

Variable / Ipragliflozin (n = 106) / Placebo (n = 44) / Placebo-adjusted mean difference (95% CI) b / P-value
Baseline / Week 24
(LOCF) / Change / Baseline / Week 24
(LOCF) / Change
HbA1c (%, NGSP) / 8.36 ± 0.657 / 7.53 ± 0.723 / −0.83 ± 0.783 / 8.22 ± 0.712 / 8.61 ± 0.978 / 0.39 ± 0.827 / −1.15 (−1.410, −0.891) / <0.001
FPG (mg/dl) / 179.8 ± 33.30 / 138.5 ± 23.11 / −41.4 ± 31.23 / 180.4 ± 31.99 / 178.0 ± 37.89 / −2.4 ± 28.40 / −39.3 (−47.91, −30.69) / <0.001
Body weight (kg) / 69.51 ± 12.360 / 67.07 ± 11.716 / −2.44 ± 2.499 / 65.11 ± 11.039 / 64.38 ± 11.293 / −0.73 ± 1.878 / −1.48 (−2.297, −0.673) / <0.001

Values are means ± standard deviation.

a Glibenclamide <5 mg/day, gliclazide <80 mg/day, or glimepiride <3 mg/day

b Analysis of covariance with treatment group as a fixed effect and baseline value as a covariate.

LOCF last observation carried forward, CI confidence interval, HbA1c hemoglobin A1c, NGSP National Glycohemoglobin Standardization Program, FPG fasting plasma glucose

Table 2 Changes in efficacy outcomes from baseline to Week 24 in patients using a high sulfonylurea dose a

Variable / Ipragliflozin (n = 59) / Placebo (n = 31) / Placebo-adjusted mean difference (95% CI) b / P-value
Baseline / Week 24
(LOCF) / Change / Baseline / Week 24
(LOCF) / Change
HbA1c (%, NGSP) / 8.41 ± 0.615 / 7.56 ± 0.578 / −0.84 ± 0.587 / 8.52 ± 0.722 / 8.75 ± 1.308 / 0.23 ± 1.137 / −1.11 (−1.459, −0.759) / <0.001
FPG (mg/dl) / 179.6 ± 30.61 / 138.2 ± 22.32 / −41.4 ± 30.29 / 169.9 ± 39.78 / 170.9 ± 41.34 / 1.0 ± 53.14 / −34.8 (−47.89, −21.69) / <0.001
Body weight (kg) / 67.45 ± 12.448 / 65.32 ± 12.602 / −2.13 ± 1.322 / 62.18 ± 11.829 / 61.08 ± 12.245 / −1.09 ± 1.650 / −1.10 (−1.753, −0.454) / 0.001

Values are means ± standard deviation.

a Glibenclamide ≥5 mg/day, gliclazide ≥80 mg/day, or glimepiride ≥3 mg/day

b Analysis of covariance with treatment group as a fixed effect and baseline value as a covariate.

LOCF last observation carried forward, CI confidence interval, HbA1c hemoglobin A1c, NGSP National Glycohemoglobin Standardization Program, FPG fasting plasma glucose

Table 3 Treatment-emergent adverse events occurring during treatment period I according to the sulfonylurea dose

Ipragliflozin / Placebo
Sulfonylurea dose / Low dose a / High dose b / Low dose a / High dose b
n / 107 / 59 / 45 / 31
All TEAEs / 82 (76.6) / 44 (74.6) / 32 (71.1) / 15 (48.4)
Drug-related TEAEs / 29 (27.1) / 10 (16.9) / 14 (31.1) / 4 (12.9)
Serious TEAEs / 2 (1.9) / 3 (5.1) / 3 (6.7) / 0 (0.0)
TEAEs leading to discontinuation / 6 (5.6) / 3 (5.1) / 7 (15.6) / 4 (12.9)
TEAEs related to
Hypoglycemia / 1 (0.9) / 1 (1.7) / 1 (2.2) / 0 (0.0)
Urinary tract infection / 0 (0.0) / 2 (3.4) / 2 (4.4) / 1 (3.2)
Genital infection / 1 (0.9) / 0 (0.0) / 3 (6.7) / 0 (0.0)
Polyuria and/or pollakiuria / 14 (13.1) / 2 (3.4) / 2 (4.4) / 0 (0.0)

Values are n (%) of patients.

a Glibenclamide <5 mg/day, gliclazide <80 mg/day, or glimepiride <3 mg/day.

b Glibenclamide ≥5 mg/day, gliclazide ≥80 mg/day, or glimepiride ≥3 mg/day.

TEAE treatment-emergent adverse event.

Supplementary Figure 1. Scatterplot for the changes in systolic blood pressure and body weight from baseline to the end of treatment period I.