J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 9, Number 7, July 2017, pages 586-595

Ipragliflozin Improves Glycemic Control and Decreases Body Fat in Patients With Type 2 Diabetes Mellitus

Figure 1. Effect of ipragliflozin on body weight and waist circumference. (a) Change in body weight after the start of ipragliflozin therapy (n = 295). (b) Change in waist circumference after the start of ipragliflozin therapy (n = 334). (c) Stratified analysis of the body weight changes in patients receiving ipragliflozin concomitantly with an SU, insulin, or TZD (n = 152) and patients receiving ipragliflozin without concomitant use of these drugs (n = 143). (d) Stratified analysis of the waist circumference changes in patients receiving ipragliflozin concomitantly with an SU, insulin, or TZD (n = 171) and patients receiving ipragliflozin without concomitant use of these drugs (n = 163). (e) Changes in body fat mass and fat-free body mass measured by a body composition analyzer from the start of ipragliflozin administration (body fat mass, n = 295; fat-free body mass, n = 295). (f) Changes in body composition measured by a body composition analyzer from the initiation of ipragliflozin treatment. Significant differences in week 4, week 12, and week 24 relative to the start of administration: ***P < 0.001; **P < 0.01; *P < 0.05, respectively. SU: sulfonylurea; TZD: thiazolidinedione.

**Table 1.** Baseline Characteristics of the Patients
	n (%)	Mean ± standard deviation
Gender
Male	234 (51.9)
Female	217 (48.1)
Age, years	451 (100.0)	55.5 ± 11.6
Body weight, kg	451 (100.0)	78.6 ± 16.8
Body mass index, kg/m²	451 (100.0)	29.4 ± 5.3
< 25	84 (18.6)
≥ 25 to < 30	191 (42.4)
≥ 30	176 (39.0)
Waist circumference, cm	451 (100.0)	99.8 ± 12.0
Duration of diabetes, years	451 (100.0)	9.6 ± 7.4
Complications of diabetes
Diabetic nephropathy	131 (29.0)
Diabetic retinopathy	62 (13.7)
Diabetic neuropathy	60 (13.3)
Concomitant diseases
Dyslipidemia	294 (65.2)
Hypertension	259 (57.4)
Fatty liver	218 (48.3)
Cataract	76 (16.9)
Prescribing status
Naive	79 (17.5)
Concomitant use	335 (74.3)
Switching	37 (8.2)
Concomitant antidiabetic therapy
Dipeptidyl peptidase 4 inhibitor	245 (73.1)
Biguanide	216 (64.5)
Sulfonylurea	123 (36.7)
Insulin	72 (21.5)
Thiazolidinedione	46 (13.7)
α-glucosidase inhibitor	33 (9.9)
Glinide	16 (4.8)
Glucagon-like peptide 1 analogue	4 (1.2)
Others	26 (7.8)

Table 1. Baseline Characteristics of the Patients

n (%)

Mean ± standard deviation

Gender

Male

234 (51.9)

Female

217 (48.1)

Age, years

451 (100.0)

55.5 ± 11.6

Body weight, kg

451 (100.0)

78.6 ± 16.8

Body mass index, kg/m²

451 (100.0)

29.4 ± 5.3

< 25

84 (18.6)

≥ 25 to < 30

191 (42.4)

≥ 30

176 (39.0)

Waist circumference, cm

451 (100.0)

99.8 ± 12.0

Duration of diabetes, years

451 (100.0)

9.6 ± 7.4

Complications of diabetes

Diabetic nephropathy

131 (29.0)

Diabetic retinopathy

62 (13.7)

Diabetic neuropathy

60 (13.3)

Concomitant diseases

Dyslipidemia

294 (65.2)

Hypertension

259 (57.4)

Fatty liver

218 (48.3)

Cataract

76 (16.9)

Prescribing status

Naive

79 (17.5)

Concomitant use

335 (74.3)

Switching

37 (8.2)

Concomitant antidiabetic therapy

Dipeptidyl peptidase 4 inhibitor

245 (73.1)

Biguanide

216 (64.5)

Sulfonylurea

123 (36.7)

Insulin

72 (21.5)

Thiazolidinedione

46 (13.7)

α-glucosidase inhibitor

33 (9.9)

Glinide

16 (4.8)

Glucagon-like peptide 1 analogue

4 (1.2)

Others

26 (7.8)

**Table 2.** Changes in Glycemic Control Parameters from Initiation of Ipragliflozin Therapy
	n	Week 0	Week 4	Week 12	Week 24
Data are shown as the mean ± standard deviation. Analysis of variance vs. week 0, *P < 0.001, P < 0.01.
Hemoglobin A1c, %	374	8.07 ± 1.46	7.66 ± 1.22*** (-0.41 ± 0.60)	7.31 ± 1.11*** (-0.76 ± 1.07)	7.26 ± 1.05*** (-0.81 ± 1.11)
Fasting blood glucose, mg/dL	114	156.0 ± 44.6	136.7 ± 36.8*** (-19.3 ± 37.7)	132.2 ± 33.4*** (-23.8 ± 35.2)	136.0 ± 33.2*** (-20.0 ± 38.0)
Postprandial blood glucose, mg/dL	137	184.7 ± 74.0	156.9 ± 58.7*** (-27.8 ± 74.6)	153.4 ± 62.6*** (-31.3 ± 70.9)	147.3 ± 49.5*** (-37.4 ± 76.7)
Homeostatic model assessment of insulin resistance	51	4.46 ± 3.69	3.14 ± 2.27** (-1.32 ± 2.83)	3.16 ± 2.36*** (-1.30 ± 1.96)	3.28 ± 2.70** (-1.18 ± 2.11)
Homeostatic model assessment of beta cell function	51	46.49 ± 44.66	50.70 ± 44.66 (4.21 ± 26.69)	52.94 ± 43.05 (6.45 ± 24.39)	49.48 ± 43.55 (2.99 ± 20.15)
Insulin, μU/mL	51	12.65 ± 9.06	11.82 ± 9.60 (-0.84 ± 7.69)	13.89 ± 21.07 (1.24 ± 16.82)	12.42 ± 13.60 (-0.23 ± 9.84)
C-peptide immunoreactivity, ng/mL	51	3.123 ± 2.060	3.348 ± 2.793 (0.224 ± 2.553)	3.120 ± 2.283 (-0.004 ± 1.813)	3.073 ± 2.026 (-0.050 ± 1.907)

Table 2. Changes in Glycemic Control Parameters from Initiation of Ipragliflozin Therapy

Week 0

Week 4

Week 12

Week 24

Data are shown as the mean ± standard deviation. Analysis of variance vs. week 0, ***P < 0.001, **P < 0.01.

Hemoglobin A1c, %

374

8.07 ± 1.46

7.66 ± 1.22*** (-0.41 ± 0.60)

7.31 ± 1.11*** (-0.76 ± 1.07)

7.26 ± 1.05*** (-0.81 ± 1.11)

Fasting blood glucose, mg/dL

114

156.0 ± 44.6

136.7 ± 36.8*** (-19.3 ± 37.7)

132.2 ± 33.4*** (-23.8 ± 35.2)

136.0 ± 33.2*** (-20.0 ± 38.0)

Postprandial blood glucose, mg/dL

137

184.7 ± 74.0

156.9 ± 58.7*** (-27.8 ± 74.6)

153.4 ± 62.6*** (-31.3 ± 70.9)

147.3 ± 49.5*** (-37.4 ± 76.7)

Homeostatic model assessment of insulin resistance

4.46 ± 3.69

3.14 ± 2.27** (-1.32 ± 2.83)

3.16 ± 2.36*** (-1.30 ± 1.96)

3.28 ± 2.70** (-1.18 ± 2.11)

Homeostatic model assessment of beta cell function

46.49 ± 44.66

50.70 ± 44.66 (4.21 ± 26.69)

52.94 ± 43.05 (6.45 ± 24.39)

49.48 ± 43.55 (2.99 ± 20.15)

Insulin, μU/mL

12.65 ± 9.06

11.82 ± 9.60 (-0.84 ± 7.69)

13.89 ± 21.07 (1.24 ± 16.82)

12.42 ± 13.60 (-0.23 ± 9.84)

C-peptide immunoreactivity, ng/mL

3.123 ± 2.060

3.348 ± 2.793 (0.224 ± 2.553)

3.120 ± 2.283 (-0.004 ± 1.813)

3.073 ± 2.026 (-0.050 ± 1.907)

**Table 3.** Changes in Body Composition after Initiation of Ipragliflozin Therapy
	Week 0	Week 4	Week 12	Week 24
n = 373. Data are shown as the mean ± standard deviation. Analysis of variance vs. week 0, *P < 0.001, P < 0.01, *P < 0.05.
Body weight, kg	79.6 ± 16.6	78.4 ± 16.4*** (-1.2 ± 1.4)	77.5 ± 16.2*** (-2.1 ± 2.6)	77.0 ± 16.2*** (-2.6 ± 3.3)
Body fat mass, kg	25.1 ± 8.9	24.4 ± 8.7*** (-0.7 ± 1.8)	23.7 ± 8.6*** (-1.4 ± 2.2)	23.2 ± 8.7*** (-1.9 ± 2.9)
Fat-free body mass, kg	54.5 ± 10.9	54.0 ± 10.9*** (-0.5 ± 1.9)	53.8 ± 10.9*** (-0.7 ± 2.5)	53.8 ± 10.7*** (-0.6 ± 2.8)
Muscle mass, kg	49.9 ± 10.1	49.5 ± 10.1*** (-0.4 ± 1.9)	49.4 ± 10.1*** (-0.6 ± 2.4)	49.4 ± 9.9** (-0.5 ± 2.6)
Body water mass, kg	39.2 ± 7.8	38.8 ± 7.8*** (-0.4 ± 1.5)	38.7 ± 7.9*** (-0.5 ± 1.9)	38.7 ± 7.7*** (-0.5 ± 2.1)
Extracellular water mass, kg	15.6 ± 3.2	15.3 ± 3.1*** (-0.3 ± 1.3)	15.1 ± 3.2*** (-0.6 ± 1.5)	15.1 ± 3.0*** (-0.5 ± 1.6)
Intracellular water mass, kg	23.6 ± 4.9	23.6 ± 5.0 (-0.1 ± 1.6)	23.7 ± 5.1 (0.0 ± 1.8)	23.6 ± 5.0 (-0.0 ± 2.0)
Protein mass, kg	10.7 ± 2.3	10.7 ± 2.3* (-0.1 ± 0.5)	10.7 ± 2.3 (-0.1 ± 0.6)	10.7 ± 2.2 (-0.1 ± 0.7)
Mineral mass, kg	4.5 ± 0.9	4.5 ± 0.9*** (-0.1 ± 0.1)	4.4 ± 0.9*** (-0.1 ± 0.2)	4.4 ± 0.9*** (-0.1 ± 0.2)
Muscle mass (trunk), kg	24.3 ± 4.9	24.1 ± 4.9*** (-0.2 ± 0.8)	24.0 ± 4.9*** (-0.3 ± 1.0)	24.0 ± 4.8*** (-0.3 ± 1.1)
Muscle mass (upper limbs), kg	3.47 ± 0.75	3.45 ± 0.76 (-0.03 ± 0.20)	3.44 ± 0.80 (-0.04 ± 0.34)	3.44 ± 0.76 (-0.04 ± 0.30)
Muscle mass (lower limbs), kg	9.36 ± 1.86	9.27 ± 1.86** (-0.09 ± 0.47)	9.27 ± 1.88* (-0.09 ± 0.57)	9.28 ± 1.84 (-0.08 ± 0.59)
Body mass index, kg/m²	29.6 ± 5.1	29.2 ± 5.0*** (-0.4 ± 0.5)	28.9 ± 4.9*** (-0.8 ± 1.0)	28.7 ± 4.9*** (-1.0 ± 1.2)
Body fat percentage, %	31.1 ± 7.0	30.7 ± 7.1** (-0.4 ± 2.1)	30.2 ± 7.2*** (-1.0 ± 2.4)	29.6 ± 7.3*** (-1.5 ± 3.2)
Visceral fat/subcutaneous fat ratio, %	0.436 ± 0.042	0.433 ± 0.043** (-0.003 ± 0.017)	0.428 ± 0.045*** (-0.008 ± 0.020)	0.424 ± 0.048*** (-0.012 ± 0.026)

Table 3. Changes in Body Composition after Initiation of Ipragliflozin Therapy

Week 0

Week 4

Week 12

Week 24

n = 373. Data are shown as the mean ± standard deviation. Analysis of variance vs. week 0, ***P < 0.001, **P < 0.01, *P < 0.05.

Body weight, kg

79.6 ± 16.6

78.4 ± 16.4*** (-1.2 ± 1.4)

77.5 ± 16.2*** (-2.1 ± 2.6)

77.0 ± 16.2*** (-2.6 ± 3.3)

Body fat mass, kg

25.1 ± 8.9

24.4 ± 8.7*** (-0.7 ± 1.8)

23.7 ± 8.6*** (-1.4 ± 2.2)

23.2 ± 8.7*** (-1.9 ± 2.9)

Fat-free body mass, kg

54.5 ± 10.9

54.0 ± 10.9*** (-0.5 ± 1.9)

53.8 ± 10.9*** (-0.7 ± 2.5)

53.8 ± 10.7*** (-0.6 ± 2.8)

Muscle mass, kg

49.9 ± 10.1

49.5 ± 10.1*** (-0.4 ± 1.9)

49.4 ± 10.1*** (-0.6 ± 2.4)

49.4 ± 9.9** (-0.5 ± 2.6)

Body water mass, kg

39.2 ± 7.8

38.8 ± 7.8*** (-0.4 ± 1.5)

38.7 ± 7.9*** (-0.5 ± 1.9)

38.7 ± 7.7*** (-0.5 ± 2.1)

Extracellular water mass, kg

15.6 ± 3.2

15.3 ± 3.1*** (-0.3 ± 1.3)

15.1 ± 3.2*** (-0.6 ± 1.5)

15.1 ± 3.0*** (-0.5 ± 1.6)

Intracellular water mass, kg

23.6 ± 4.9

23.6 ± 5.0 (-0.1 ± 1.6)

23.7 ± 5.1 (0.0 ± 1.8)

23.6 ± 5.0 (-0.0 ± 2.0)

Protein mass, kg

10.7 ± 2.3

10.7 ± 2.3* (-0.1 ± 0.5)

10.7 ± 2.3 (-0.1 ± 0.6)

10.7 ± 2.2 (-0.1 ± 0.7)

Mineral mass, kg

4.5 ± 0.9

4.5 ± 0.9*** (-0.1 ± 0.1)

4.4 ± 0.9*** (-0.1 ± 0.2)

Muscle mass (trunk), kg

24.3 ± 4.9

24.1 ± 4.9*** (-0.2 ± 0.8)

24.0 ± 4.9*** (-0.3 ± 1.0)

24.0 ± 4.8*** (-0.3 ± 1.1)

Muscle mass (upper limbs), kg

3.47 ± 0.75

3.45 ± 0.76 (-0.03 ± 0.20)

3.44 ± 0.80 (-0.04 ± 0.34)

3.44 ± 0.76 (-0.04 ± 0.30)

Muscle mass (lower limbs), kg

9.36 ± 1.86

9.27 ± 1.86** (-0.09 ± 0.47)

9.27 ± 1.88* (-0.09 ± 0.57)

9.28 ± 1.84 (-0.08 ± 0.59)

Body mass index, kg/m²

29.6 ± 5.1

29.2 ± 5.0*** (-0.4 ± 0.5)

28.9 ± 4.9*** (-0.8 ± 1.0)

28.7 ± 4.9*** (-1.0 ± 1.2)

Body fat percentage, %

31.1 ± 7.0

30.7 ± 7.1** (-0.4 ± 2.1)

30.2 ± 7.2*** (-1.0 ± 2.4)

29.6 ± 7.3*** (-1.5 ± 3.2)

Visceral fat/subcutaneous fat ratio, %

0.436 ± 0.042

0.433 ± 0.043** (-0.003 ± 0.017)

0.428 ± 0.045*** (-0.008 ± 0.020)

0.424 ± 0.048*** (-0.012 ± 0.026)

**Table 4.** Changes in Blood Pressure and Fasting Serum Lipids after Initiation of Ipragliflozin Therapy
	n	Week 0	Week 4	Week 12	Week 24
Data are shown as the mean ± standard deviation. Analysis of variance vs. week 0, *P < 0.001, P < 0.01, *P < 0.05.
Systolic blood pressure, mm Hg	369	133.1 ± 17.1	127.9 ± 16.4*** (-5.1 ± 14.9)	128.5 ± 16.5*** (-4.5 ± 16.1)	128.2 ± 16.8*** (-4.9 ± 16.8)
Diastolic blood pressure, mm Hg	369	79.1 ± 10.9	76.5 ± 10.8*** (-2.6 ± 9.8)	76.6 ± 11.1*** (-2.5 ± 10.0)	76.8 ± 11.7*** (-2.3 ± 10.6)
Total cholesterol, mg/dL	111	201.4 ± 36.7	197.9 ± 37.7 (-3.5 ± 25.0)	201.6 ± 35.8 (0.2 ± 26.0)	203.3 ± 38.9 (1.9 ± 29.0)
Low-density lipoprotein cholesterol, mg/dL	100	117.0 ± 29.9	116.9 ± 31.9 (-0.1 ± 20.6)	116.6 ± 29.3 (-0.3 ± 24.7)	117.5 ± 31.6 (0.5 ± 26.7)
High-density lipoprotein cholesterol, mg/dL	112	52.6 ± 11.8	52.5 ± 11.5 (-0.2 ± 5.7)	56.5 ± 18.8 (3.9 ± 16.6)	57.7 ± 16.5*** (5.1 ± 12.3)
Triglycerides, mg/dL	112	164.1 ± 101.7	145.6 ± 95.0* (-18.5 ± 65.1)	140.8 ± 92.6** (-23.4 ± 76.3)	136.8 ± 94.7*** (-27.3 ± 68.7)
Non-high-density lipoprotein cholesterol, mg/dL	112	148.8 ± 37.0	145.4 ± 37.7 (-3.3 ± 23.4)	145.1 ± 36.5 (-3.7 ± 28.4)	145.6 ± 38.1 (-3.1 ± 30.0)
Free fatty acids, μEq/L	112	712.4 ± 259.1	755.2 ± 253.1 (42.8 ± 239.8)	719.1 ± 288.1 (6.7 ± 309.8)	732.5 ± 287.2 (20.1 ± 253.3)

Table 4. Changes in Blood Pressure and Fasting Serum Lipids after Initiation of Ipragliflozin Therapy

Week 0

Week 4

Week 12

Week 24

Data are shown as the mean ± standard deviation. Analysis of variance vs. week 0, ***P < 0.001, **P < 0.01, *P < 0.05.

Systolic blood pressure, mm Hg

369

133.1 ± 17.1

127.9 ± 16.4*** (-5.1 ± 14.9)

128.5 ± 16.5*** (-4.5 ± 16.1)

128.2 ± 16.8*** (-4.9 ± 16.8)

Diastolic blood pressure, mm Hg

369

79.1 ± 10.9

76.5 ± 10.8*** (-2.6 ± 9.8)

76.6 ± 11.1*** (-2.5 ± 10.0)

76.8 ± 11.7*** (-2.3 ± 10.6)

Total cholesterol, mg/dL

111

201.4 ± 36.7

197.9 ± 37.7 (-3.5 ± 25.0)

201.6 ± 35.8 (0.2 ± 26.0)

203.3 ± 38.9 (1.9 ± 29.0)

Low-density lipoprotein cholesterol, mg/dL

100

117.0 ± 29.9

116.9 ± 31.9 (-0.1 ± 20.6)

116.6 ± 29.3 (-0.3 ± 24.7)

117.5 ± 31.6 (0.5 ± 26.7)

High-density lipoprotein cholesterol, mg/dL

112

52.6 ± 11.8

52.5 ± 11.5 (-0.2 ± 5.7)

56.5 ± 18.8 (3.9 ± 16.6)

57.7 ± 16.5*** (5.1 ± 12.3)

Triglycerides, mg/dL

112

164.1 ± 101.7

145.6 ± 95.0* (-18.5 ± 65.1)

140.8 ± 92.6** (-23.4 ± 76.3)

136.8 ± 94.7*** (-27.3 ± 68.7)

Non-high-density lipoprotein cholesterol, mg/dL

112

148.8 ± 37.0

145.4 ± 37.7 (-3.3 ± 23.4)

145.1 ± 36.5 (-3.7 ± 28.4)

145.6 ± 38.1 (-3.1 ± 30.0)

Free fatty acids, μEq/L

112

712.4 ± 259.1

755.2 ± 253.1 (42.8 ± 239.8)

719.1 ± 288.1 (6.7 ± 309.8)

732.5 ± 287.2 (20.1 ± 253.3)

**Table 5.** Changes in Other Parameters after Initiation of Ipragliflozin Therapy
	Week 0	Week 4	Week 12	Week 24
n = 357. Results are shown as the mean ± standard deviation. Analysis of variance vs. week 0, *P < 0.001, P < 0.01, *P < 0.05.
Alanine aminotransferase, IU/L	39.8 ± 30.3	36.6 ± 28.4** (-3.1 ± 15.9)	32.8 ± 22.3*** (-7.0 ± 21.4)	29.6 ± 18.7*** (-10.2 ± 22.9)
Aspartate transaminase, IU/L	32.4 ± 24.7	30.5 ± 23.1** (-1.9 ± 10.5)	27.7 ± 16.5*** (-4.7 ± 16.0)	25.1 ± 11.8*** (-7.3 ± 20.1)
Lactate dehydrogenase, IU/L	202.7 ± 41.7	196.4 ± 40.9** (-6.3 ± 33.5)	192.2 ± 35.8*** (-10.5 ± 34.7)	190.7 ± 39.7*** (-12.0 ± 40.4)
γ-glutamyl transpeptidase, IU/L	58.2 ± 60.0	49.4 ± 52.2*** (-8.9 ± 26.2)	45.0 ± 42.6*** (-13.2 ± 38.4)	42.5 ± 39.7*** (-15.7 ± 41.8)
Alkaline phosphatase, IU/L	238.9 ± 82.1	228.1 ± 73.7*** (-10.8 ± 40.4)	227.5 ± 68.9*** (-11.4 ± 45.3)	225.8 ± 64.5*** (-13.0 ± 49.9)
Blood urea nitrogen, mg/dL	14.2 ± 4.4	15.1 ± 4.5*** (0.9 ± 3.2)	15.3 ± 4.3*** (1.1 ± 3.4)	15.7 ± 4.5*** (1.5 ± 3.6)
Serum creatinine, mg/dL	0.71 ± 0.20	0.74 ± 0.22*** (0.03 ± 0.09)	0.72 ± 0.21** (0.02 ± 0.08)	0.73 ± 0.21** (0.02 ± 0.10)
Uric acid, mg/dL	5.4 ± 1.2	4.9 ± 1.3*** (-0.4 ± 0.9)	5.0 ± 1.2*** (-0.4 ± 0.8)	4.9 ± 1.2*** (-0.4 ± 0.9)
Estimated glomerular filtration rate, mL/min/1.73 m²	84.0 ± 21.5	80.8 ± 21.9*** (-3.2 ± 10.2)	82.4 ± 21.4* (-1.7 ± 10.4)	82.3 ± 21.3* (-1.7 ± 10.8)
Hematocrit, %	43.4 ± 4.1	44.5 ± 4.3*** (1.2 ± 1.9)	45.4 ± 4.2*** (2.1 ± 2.4)	45.5 ± 4.1*** (2.1 ± 2.5)
Na⁺, mEq/L	140.50 ± 2.25	140.80 ± 2.02* (0.30 ± 2.0)	140.80 ± 1.88 (0.30 ± 2.1)	140.70 ± 1.93 (0.20 ± 2.3)
K⁺, mEq/L	4.12 ± 0.55	4.12 ± 0.51 (0.00 ± 0.43)	4.18 ± 0.50 (0.06 ± 0.57)	4.35 ± 0.54*** (0.23 ± 0.73)
Cl^-, mEq/L	102.3 ± 2.9	102.8 ± 2.8** (0.5 ± 2.3)	102.5 ± 2.6 (0.2 ± 2.5)	102.5 ± 2.7 (0.2 ± 2.6)
Ca²⁺, mEq/L	9.4 ± 0.4	9.4 ± 0.4 (0.0 ± 0.3)	9.4 ± 0.4 (-0.0 ± 0.4)	9.4 ± 0.4 (0.0 ± 0.3)
Pi, mg/dL	3.3 ± 0.6	3.5 ± 0.6*** (0.2 ± 0.6)	3.5 ± 0.7*** (0.2 ± 0.6)	3.4 ± 0.6** (0.1 ± 0.6)
Blood ketone bodies, mmol/L	0.30 ± 1.43	0.42 ± 2.04* (0.12 ± 0.65)	0.43 ± 2.34 (0.14 ± 0.95)	0.44 ± 2.69 (0.14 ± 1.27)

Table 5. Changes in Other Parameters after Initiation of Ipragliflozin Therapy

Week 0

Week 4

Week 12

Week 24

n = 357. Results are shown as the mean ± standard deviation. Analysis of variance vs. week 0, ***P < 0.001, **P < 0.01, *P < 0.05.

Alanine aminotransferase, IU/L

39.8 ± 30.3

36.6 ± 28.4** (-3.1 ± 15.9)

32.8 ± 22.3*** (-7.0 ± 21.4)

29.6 ± 18.7*** (-10.2 ± 22.9)

Aspartate transaminase, IU/L

32.4 ± 24.7

30.5 ± 23.1** (-1.9 ± 10.5)

27.7 ± 16.5*** (-4.7 ± 16.0)

25.1 ± 11.8*** (-7.3 ± 20.1)

Lactate dehydrogenase, IU/L

202.7 ± 41.7

196.4 ± 40.9** (-6.3 ± 33.5)

192.2 ± 35.8*** (-10.5 ± 34.7)

190.7 ± 39.7*** (-12.0 ± 40.4)

γ-glutamyl transpeptidase, IU/L

58.2 ± 60.0

49.4 ± 52.2*** (-8.9 ± 26.2)

45.0 ± 42.6*** (-13.2 ± 38.4)

42.5 ± 39.7*** (-15.7 ± 41.8)

Alkaline phosphatase, IU/L

238.9 ± 82.1

228.1 ± 73.7*** (-10.8 ± 40.4)

227.5 ± 68.9*** (-11.4 ± 45.3)

225.8 ± 64.5*** (-13.0 ± 49.9)

Blood urea nitrogen, mg/dL

14.2 ± 4.4

15.1 ± 4.5*** (0.9 ± 3.2)

15.3 ± 4.3*** (1.1 ± 3.4)

15.7 ± 4.5*** (1.5 ± 3.6)

Serum creatinine, mg/dL

0.71 ± 0.20

0.74 ± 0.22*** (0.03 ± 0.09)

0.72 ± 0.21** (0.02 ± 0.08)

0.73 ± 0.21** (0.02 ± 0.10)

Uric acid, mg/dL

5.4 ± 1.2

4.9 ± 1.3*** (-0.4 ± 0.9)

5.0 ± 1.2*** (-0.4 ± 0.8)

4.9 ± 1.2*** (-0.4 ± 0.9)

Estimated glomerular filtration rate, mL/min/1.73 m²

84.0 ± 21.5

80.8 ± 21.9*** (-3.2 ± 10.2)

82.4 ± 21.4* (-1.7 ± 10.4)

82.3 ± 21.3* (-1.7 ± 10.8)

Hematocrit, %

43.4 ± 4.1

44.5 ± 4.3*** (1.2 ± 1.9)

45.4 ± 4.2*** (2.1 ± 2.4)

45.5 ± 4.1*** (2.1 ± 2.5)

Na⁺, mEq/L

140.50 ± 2.25

140.80 ± 2.02* (0.30 ± 2.0)

140.80 ± 1.88 (0.30 ± 2.1)

140.70 ± 1.93 (0.20 ± 2.3)

K⁺, mEq/L

4.12 ± 0.55

4.12 ± 0.51 (0.00 ± 0.43)

4.18 ± 0.50 (0.06 ± 0.57)

4.35 ± 0.54*** (0.23 ± 0.73)

Cl^-, mEq/L

102.3 ± 2.9

102.8 ± 2.8** (0.5 ± 2.3)

102.5 ± 2.6 (0.2 ± 2.5)

102.5 ± 2.7 (0.2 ± 2.6)

Ca²⁺, mEq/L

9.4 ± 0.4

9.4 ± 0.4 (0.0 ± 0.3)

9.4 ± 0.4 (-0.0 ± 0.4)

9.4 ± 0.4 (0.0 ± 0.3)

Pi, mg/dL

3.3 ± 0.6

3.5 ± 0.6*** (0.2 ± 0.6)

3.5 ± 0.7*** (0.2 ± 0.6)

3.4 ± 0.6** (0.1 ± 0.6)

Blood ketone bodies, mmol/L

0.30 ± 1.43

0.42 ± 2.04* (0.12 ± 0.65)

0.43 ± 2.34 (0.14 ± 0.95)

0.44 ± 2.69 (0.14 ± 1.27)