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 9, September 2017, pages 793-801

Effectiveness of Ipragliflozin for Reducing Hemoglobin A1c in Patients With a Shorter Type 2 Diabetes Duration: Interim Report of the ASSIGN-K Study

**Table 1.** Clinical Characteristics of the Patients
Number of patients	451
*National Glycohemoglobin Standardization Program value. SD: standard deviation.
Age, years, mean ± SD	55.5 ± 11.6
< 65 years, n (%)	348 (77.2)
≥ 65 years, n (%)	103 (22.8)
Sex
Male, n (%)	234 (51.9)
Female, n (%)	217 (48.1)
Body weight, kg, mean ± SD	78.6 ± 16.8
Body mass index, kg/m², mean ± SD	29.4 ± 5.3
Waist circumference, cm	99.8 ± 12.0
Hemoglobin A1c, %,* mean ± SD (n)	8.01 ± 1.43 (451)
Fasting blood glucose, mg/dL, mean ± SD (n)	156.4 ± 48.0 (197)
Postprandial blood glucose, mg/dL, mean ± SD (n)	179.6 ± 78.9 (252)
Duration of diabetes, years, mean ± SD (n)	9.6 ± 7.4 (451)
Systolic blood pressure, mm Hg, mean ± SD (n)	133.1 ± 17.2 (448)
Diastolic blood pressure, mm Hg, mean ± SD (n)	79.2 ± 11.1 (448)
Estimated glomerular filtration rate, mL/min/1.73 m², mean ± SD (n)	83.4 ± 21.7 (445)
< 60 mL/min/1.73 m², n (%)	59 (13.1)
≥ 60 mL/min/1.73 m², n (%)	386 (85.6)
Complications of diabetes
Diabetic nephropathy	131 (29.0)
Diabetic retinopathy	62 (13.7)
Diabetic neuropathy	60 (13.3)
Prescribing pattern
Initial treatment	79 (17.5)
Concomitant use	335 (74.3)
Switching	37(8.2)

Table 1. Clinical Characteristics of the Patients

Number of patients

451

*National Glycohemoglobin Standardization Program value. SD: standard deviation.

Age, years, mean ± SD

55.5 ± 11.6

< 65 years, n (%)

348 (77.2)

≥ 65 years, n (%)

103 (22.8)

Sex

Male, n (%)

234 (51.9)

Female, n (%)

217 (48.1)

Body weight, kg, mean ± SD

78.6 ± 16.8

Body mass index, kg/m², mean ± SD

29.4 ± 5.3

Waist circumference, cm

99.8 ± 12.0

Hemoglobin A1c, %,* mean ± SD (n)

8.01 ± 1.43 (451)

Fasting blood glucose, mg/dL, mean ± SD (n)

156.4 ± 48.0 (197)

Postprandial blood glucose, mg/dL, mean ± SD (n)

179.6 ± 78.9 (252)

Duration of diabetes, years, mean ± SD (n)

9.6 ± 7.4 (451)

Systolic blood pressure, mm Hg, mean ± SD (n)

133.1 ± 17.2 (448)

Diastolic blood pressure, mm Hg, mean ± SD (n)

79.2 ± 11.1 (448)

Estimated glomerular filtration rate, mL/min/1.73 m², mean ± SD (n)

83.4 ± 21.7 (445)

< 60 mL/min/1.73 m², n (%)

59 (13.1)

≥ 60 mL/min/1.73 m², n (%)

386 (85.6)

Complications of diabetes

Diabetic nephropathy

131 (29.0)

Diabetic retinopathy

62 (13.7)

Diabetic neuropathy

60 (13.3)

Prescribing pattern

Initial treatment

79 (17.5)

Concomitant use

335 (74.3)

Switching

37(8.2)

**Table 2.** Changes in Various Parameters up to Week 24
	n	Baseline	Week 4	Week 12	Week 24
Analysis of variance vs. baseline * P < 0.001, P < 0.01.
Hemoglobin A1c, %	374	8.07 ± 1.46	7.66 ± 1.22***	7.31 ± 1.11***	7.26 ± 1.05***
Fasting blood glucose, mg/dL	114	156.0 ± 44.6	136.7 ± 36.8***	132.2 ± 33.4***	136.0 ± 33.2***
Postprandial blood glucose, mg/dL	137	184.7 ± 74.0	156.9 ± 58.7***	153.4 ± 62.6***	147.3 ± 49.5***
Homeostasis model assessment of insulin resistance	51	4.46 ± 3.96	3.14 ± 2.27***	3.16 ± 2.36***	3.28 ± 2.70***
Body weight, kg	373	79.6 ± 16.6	78.4 ± 16.4***	77.5 ± 16.2***	77.0 ± 16.2***
Body mass index, kg/m²	373	29.6 ± 5.1	29.2 ± 5.0***	28.9 ± 4.9***	28.7 ± 4.9***
Waist circumference, cm	342	99.9 ± 12.1	98.9 ± 12.9**	98.0 ± 11.8***	97.0 ± 11.7***
Systolic blood pressure, mm Hg	369	133.1 ± 17.1	127.9 ± 16.4***	128.5 ± 16.5***	128.2 ± 16.8***
Diastolic blood pressure, mm Hg	369	79.1 ± 10.9	76.5 ± 10.8***	76.6 ± 11.1***	76.8 ± 11.7***
Pulse rate, beats/min	295	78.6 ± 12.7	79.6 ± 12.2	79.3 ± 12.0	78.6 ± 12.2

Table 2. Changes in Various Parameters up to Week 24

Baseline

Week 4

Week 12

Week 24

Analysis of variance vs. baseline *** P < 0.001, ** P < 0.01.

Hemoglobin A1c, %

374

8.07 ± 1.46

7.66 ± 1.22***

7.31 ± 1.11***

7.26 ± 1.05***

Fasting blood glucose, mg/dL

114

156.0 ± 44.6

136.7 ± 36.8***

132.2 ± 33.4***

136.0 ± 33.2***

Postprandial blood glucose, mg/dL

137

184.7 ± 74.0

156.9 ± 58.7***

153.4 ± 62.6***

147.3 ± 49.5***

Homeostasis model assessment of insulin resistance

4.46 ± 3.96

3.14 ± 2.27***

3.16 ± 2.36***

3.28 ± 2.70***

Body weight, kg

373

79.6 ± 16.6

78.4 ± 16.4***

77.5 ± 16.2***

77.0 ± 16.2***

Body mass index, kg/m²

373

29.6 ± 5.1

29.2 ± 5.0***

28.9 ± 4.9***

28.7 ± 4.9***

Waist circumference, cm

342

99.9 ± 12.1

98.9 ± 12.9**

98.0 ± 11.8***

97.0 ± 11.7***

Systolic blood pressure, mm Hg

369

133.1 ± 17.1

127.9 ± 16.4***

128.5 ± 16.5***

128.2 ± 16.8***

Diastolic blood pressure, mm Hg

369

79.1 ± 10.9

76.5 ± 10.8***

76.6 ± 11.1***

76.8 ± 11.7***

Pulse rate, beats/min

295

78.6 ± 12.7

79.6 ± 12.2

79.3 ± 12.0

78.6 ± 12.2

**Table 3.** Influence of Patient Characteristics on Hemoglobin A1c
	n	Baseline	Week 4	Week 12	Week 24
Analysis of variance vs. baseline *P < 0.001, P < 0.01, *P < 0.05.
Age
< 65 years	294	8.19 ± 1.53	7.75 ± 1.27***	7.38 ± 1.15***	7.31 ± 1.09***
≥ 65 years	73	7.59 ± 1.01	7.28 ± 0.89*	7.03 ± 0.86***	7.04 ± 0.83***
Sex
Male	194	8.09 ± 1.51	7.62 ± 1.22***	7.18 ± 1.04***	7.17 ± 1.04***
Female	173	8.05 ± 1.39	7.70 ± 1.21***	7.48 ± 1.17***	7.35 ± 1.06***
Baseline body mass index (kg/m²)
< 25	72	8.18 ± 1.66	7.58 ± 1.17***	7.10 ± 0.99***	7.13 ± 0.95***
≥ 25 and < 30	153	7.99 ± 1.47	7.64 ± 1.26***	7.36 ± 1.15***	7.34 ± 1.11***
≥ 30	142	8.10 ± 1.36	7.71 ± 1.23***	7.36 ± 1.14***	7.23 ± 1.06***
Baseline hemoglobin A1c (%)
< 7.0	80	6.52 ± 0.31	6.43 ± 0.48	6.30 ± 0.41	6.34 ± 0.40
≥ 7.0 and < 8.0	129	7.47 ± 0.27	7.16 ± 0.40**	7.01 ± 0.61***	7.02 ± 0.68***
≥ 8.0	158	9.39 ± 1.24	8.69 ± 1.09***	8.06 ± 1.15***	7.91 ± 1.10***
Duration of diabetes (years)
< 5 years	100	7.91 ± 1.67	7.42 ± 1.29***	6.91 ± 1.06***	6.89 ± 0.99***
≥ 5 to < 10 years	90	8.22 ± 1.29	7.80 ± 1.05***	7.50 ± 1.03***	7.43 ± 1.03***
≥ 10 to < 15 years	76	8.21 ± 1.32	7.83 ± 1.21**	7.52 ± 1.16***	7.44 ± 1.02***
≥ 15 years	77	8.14 ± 1.41	7.76 ± 1.24*	7.51 ± 1.09***	7.48 ± 1.05***
Estimated glomerular filtration rate (mL/min/1.73 m²)
< 60	46	7.54 ± 0.99	7.26 ± 0.94***	7.05 ± 0.89***	7.08 ± 0.89***
≥ 60	318	8.14 ± 1.50	7.71 ± 1.24	7.34 ± 1.13**	7.28 ± 1.08***
Prescribing pattern
Initial treatment	46	7.33 ± 1.14	7.05 ± 1.03	6.72 ± 0.84***	6.47 ± 0.92***
Concomitant use	318	8.17 ± 1.46	7.71 ± 1.20***	7.31 ± 1.05***	7.27 ± 1.00***
Switching	46	8.48 ± 1.49	8.24 ± 1.31	8.27 ± 1.34	7.99 ± 1.18

Table 3. Influence of Patient Characteristics on Hemoglobin A1c

Baseline

Week 4

Week 12

Week 24

Analysis of variance vs. baseline ***P < 0.001, **P < 0.01, *P < 0.05.

Age

< 65 years

294

8.19 ± 1.53

7.75 ± 1.27***

7.38 ± 1.15***

7.31 ± 1.09***

≥ 65 years

7.59 ± 1.01

7.28 ± 0.89*

7.03 ± 0.86***

7.04 ± 0.83***

Sex

Male

194

8.09 ± 1.51

7.62 ± 1.22***

7.18 ± 1.04***

7.17 ± 1.04***

Female

173

8.05 ± 1.39

7.70 ± 1.21***

7.48 ± 1.17***

7.35 ± 1.06***

Baseline body mass index (kg/m²)

< 25

8.18 ± 1.66

7.58 ± 1.17***

7.10 ± 0.99***

7.13 ± 0.95***

≥ 25 and < 30

153

7.99 ± 1.47

7.64 ± 1.26***

7.36 ± 1.15***

7.34 ± 1.11***

≥ 30

142

8.10 ± 1.36

7.71 ± 1.23***

7.36 ± 1.14***

7.23 ± 1.06***

Baseline hemoglobin A1c (%)

< 7.0

6.52 ± 0.31

6.43 ± 0.48

6.30 ± 0.41

6.34 ± 0.40

≥ 7.0 and < 8.0

129

7.47 ± 0.27

7.16 ± 0.40**

7.01 ± 0.61***

7.02 ± 0.68***

≥ 8.0

158

9.39 ± 1.24

8.69 ± 1.09***

8.06 ± 1.15***

7.91 ± 1.10***

Duration of diabetes (years)

< 5 years

100

7.91 ± 1.67

7.42 ± 1.29***

6.91 ± 1.06***

6.89 ± 0.99***

≥ 5 to < 10 years

8.22 ± 1.29

7.80 ± 1.05***

7.50 ± 1.03***

7.43 ± 1.03***

≥ 10 to < 15 years

8.21 ± 1.32

7.83 ± 1.21**

7.52 ± 1.16***

7.44 ± 1.02***

≥ 15 years

8.14 ± 1.41

7.76 ± 1.24*

7.51 ± 1.09***

7.48 ± 1.05***

Estimated glomerular filtration rate (mL/min/1.73 m²)

< 60

7.54 ± 0.99

7.26 ± 0.94***

7.05 ± 0.89***

7.08 ± 0.89***

≥ 60

318

8.14 ± 1.50

7.71 ± 1.24

7.34 ± 1.13**

7.28 ± 1.08***

Prescribing pattern

Initial treatment

7.33 ± 1.14

7.05 ± 1.03

6.72 ± 0.84***

6.47 ± 0.92***

Concomitant use

318

8.17 ± 1.46

7.71 ± 1.20***

7.31 ± 1.05***

7.27 ± 1.00***

Switching

8.48 ± 1.49

8.24 ± 1.31

8.27 ± 1.34

7.99 ± 1.18

**Table 4.** Changes in Hepatic Function, Serum Lipids, and Renal Function
	n	Baseline	Week 4	Week 12	Week 24
Analysis of variance vs. baseline *P< 0.001, P < 0.01, *P < 0.05.
Aspartate aminotransferase, IU/L	354	32.4 ± 24.7	30.5 ± 23.1**	27.7 ± 21.4***	25.1 ± 11.8***
Alanine aminotransferase, IU/L	357	39.8 ± 30.3	36.6 ± 28.4**	32.8 ± 22.3***	29.6 ± 18.7***
γ-glutamyltransferase, IU/L	358	58.2 ± 60.0	49.4 ± 52.2***	45.0 ± 42.6***	42.5 ± 39.7***
Total cholesterol, mg/dL	111	201.4 ± 36.7	197.9 ± 37.7	201.6 ± 35.8	203.3 ± 38.9
High-density lipoprotein cholesterol, mg/dL	112	52.6 ± 11.8	52.5 ± 11.5	56.5 ± 18.8	57.7 ± 16.5***
Low-density lipoprotein cholesterol, mg/dL	100	117.0 ± 29.9	116.9 ± 31.9	116.6 ± 29.3	117.5 ± 31.6
Triglycerides, mg/dL	112	164.1 ± 101.7	145.6 ± 95.0*	140.8 ± 92.6**	136.8 ± 94.7***
Uric acid, mg/dL	348	5.4 ± 1.2	4.9 ± 1.3***	5.0 ± 1.2***	4.9 ± 1.2***
Estimated glomerular filtration rate, mL/min/1.73 m²	360	84.0 ± 21.5	80.8 ± 21.9**	82.4 ± 21.4*	82.3 ± 21.3*

Table 4. Changes in Hepatic Function, Serum Lipids, and Renal Function

Baseline

Week 4

Week 12

Week 24

Analysis of variance vs. baseline ***P< 0.001, **P < 0.01, *P < 0.05.

Aspartate aminotransferase, IU/L

354

32.4 ± 24.7

30.5 ± 23.1**

27.7 ± 21.4***

25.1 ± 11.8***

Alanine aminotransferase, IU/L

357

39.8 ± 30.3

36.6 ± 28.4**

32.8 ± 22.3***

29.6 ± 18.7***

γ-glutamyltransferase, IU/L

358

58.2 ± 60.0

49.4 ± 52.2***

45.0 ± 42.6***

42.5 ± 39.7***

Total cholesterol, mg/dL

111

201.4 ± 36.7

197.9 ± 37.7

201.6 ± 35.8

203.3 ± 38.9

High-density lipoprotein cholesterol, mg/dL

112

52.6 ± 11.8

52.5 ± 11.5

56.5 ± 18.8

57.7 ± 16.5***

Low-density lipoprotein cholesterol, mg/dL

100

117.0 ± 29.9

116.9 ± 31.9

116.6 ± 29.3

117.5 ± 31.6

Triglycerides, mg/dL

112

164.1 ± 101.7

145.6 ± 95.0*

140.8 ± 92.6**

136.8 ± 94.7***

Uric acid, mg/dL

348

5.4 ± 1.2

4.9 ± 1.3***

5.0 ± 1.2***

4.9 ± 1.2***

Estimated glomerular filtration rate, mL/min/1.73 m²

360

84.0 ± 21.5

80.8 ± 21.9**

82.4 ± 21.4*

82.3 ± 21.3*

**Table 5.** Multiple Regression Analysis of Factors Influencing the Change in Hemoglobin A1c in Week 24
Influence rank	Independent variable	Standardized coefficient beta	Partial regression coefficient	P value
n = 328, Stepwise analysis using the following independent variables: age, sex, duration of diabetes, baseline hemoglobin A1c, baseline body mass index, and prescribing pattern (initial monotherapy, concomitant use, or switching). Dependent variable: change in HbA1c.
	Constant	0	2.295	< 0.0001
1	Hemoglobin A1c (baseline)	-0.691	-0.519	< 0.0001
2	Switching to ipragliflozin	0.166	0.615	< 0.0001
3	Duration of diabetes	0.151	0.022	0.0002
4	Sex	0.100	0.220	0.0096
5	Age	0.076	0.007	0.0842
6	Body mass index (baseline)	0.052	0.011	0.1982

Table 5. Multiple Regression Analysis of Factors Influencing the Change in Hemoglobin A1c in Week 24

Influence rank

Independent variable

Standardized coefficient beta

Partial regression coefficient

P value

n = 328, Stepwise analysis using the following independent variables: age, sex, duration of diabetes, baseline hemoglobin A1c, baseline body mass index, and prescribing pattern (initial monotherapy, concomitant use, or switching). Dependent variable: change in HbA1c.

Constant

2.295

< 0.0001

Hemoglobin A1c (baseline)

-0.691

-0.519

< 0.0001

Switching to ipragliflozin

0.166

0.615

< 0.0001

Duration of diabetes

0.151

0.022

0.0002

Sex

0.100

0.220

0.0096

Age

0.076

0.007

0.0842

Body mass index (baseline)

0.052

0.011

0.1982

**Table 6.** Percentage of Patients Achieving Hemoglobin A1c < 7% and Their Characteristics at 24 Weeks
	< 7%	≥ 7%	P value
*Not including patients achieving hemoglobin A1c < 7% at baseline.
Number of patients (%)*	97 (33.8)	190 (66.2)	-
Female patients	40.2%	51.1%	0.0817
Age, years	54.9	54.8	0.9477
Duration of diabetes, years	9.0	10.5	0.1092
Baseline hemoglobin A1c, %	7.86	8.83	< 0.001
Baseline body mass index, kg/m²	29.14	29.39	0.7026

Table 6. Percentage of Patients Achieving Hemoglobin A1c < 7% and Their Characteristics at 24 Weeks

< 7%

≥ 7%

P value

*Not including patients achieving hemoglobin A1c < 7% at baseline.

Number of patients (%)*

97 (33.8)

190 (66.2)

Female patients

40.2%

51.1%

0.0817

Age, years

54.9

54.8

0.9477

Duration of diabetes, years

9.0

10.5

0.1092

Baseline hemoglobin A1c, %

7.86

8.83

< 0.001

Baseline body mass index, kg/m²

29.14

29.39

0.7026