J Endocrinol Metab

Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access

Article copyright, the authors; Journal compilation copyright, J Endocrinol Metab and Elmer Press Inc

Journal website http://www.jofem.org

Original Article

Volume 9, Number 3, June 2019, pages 51-62

Efficacy and Safety of Ipragliflozin in Patients With Type 2 Diabetes: ASSIGN-K Study

Figure 4. Influence of patient characteristics on HbA1c. HbA1c showed a significant decrease regardless of sex, age, disease duration, or BMI. ANOVA: analysis of variance; BMI: body mass index; HbA1c: hemoglobin A1c.

Figure 5. Influence of additional patient characteristics on HbA1c. In patients newly prescribed ipragliflozin, HbA1c showed a significant decrease until week 52. In patients with a baseline eGFR < 60, a significant decrease of HbA1c was observed until week 78, with no significant difference in week 104. In patients with a baseline HbA1c < 7%, no significant decrease of HbA1c was observed, and the change of HbA1c was smaller in patients with relatively low baseline values. ANOVA: analysis of variance; eGFR: estimated glomerular filtration rate; HbA1c: hemoglobin A1c.

Figure 7. Changes of HbA1c stratified by achievement/nonachievement of HbA1c ≤ 7% in week 104. ANOVA: analysis of variance; HbA1c: hemoglobin A1c.

Figure 8. Changes of various parameters stratified by achievement/nonachievement of HbA1c ≤ 7%. Weigh, BMI, waist circumference, and body fat all decreased significantly in the patients who achieved HbA1c ≤ 7% compared with patients who did not. ANOVA: analysis of variance; BMI: body mass index.

**Table 1.** Baseline Characteristics of the Patients
Item	N = 451
^aMean ± standard deviation. BMI: body mass index; HbA1c: hemoglobin A1c.
Sex
Male, n (%)	234 (51.9)
Female, n (%)	217 (48.1)
Age, years	55.5 ± 11.6^a
Duration of diabetes, years	9.7 ± 7.4^a
HbA1c (%)	8.01 ± 1.43^a
Fasting blood glucose (mg/dL)	156.4 ± 48.1^a
BMI (kg/ m²)	29.4 ± 5.3^a
Weight (kg)	78.6 ± 16.8^a
Waist circumference (cm)	99.8 ± 12.0^a
Complications of diabetes
Diabetic nephropathy, n (%)	131 (29.0)
Cataract, n (%)	76 (16.9)
Diabetic retinopathy, n (%)	62 (13.7)
Diabetic neuropathy, n (%)	60 (13.3)
Lifestyle-related diseases
Dyslipidemia, n (%)	294 (65.2)
Hypertension, n (%)	259 (57.4)
Fatty liver, n (%)	218 (48.3)

Table 1. Baseline Characteristics of the Patients

Item

N = 451

^aMean ± standard deviation. BMI: body mass index; HbA1c: hemoglobin A1c.

Sex

Male, n (%)

234 (51.9)

Female, n (%)

217 (48.1)

Age, years

55.5 ± 11.6^a

Duration of diabetes, years

9.7 ± 7.4^a

HbA1c (%)

8.01 ± 1.43^a

Fasting blood glucose (mg/dL)

156.4 ± 48.1^a

BMI (kg/ m²)

29.4 ± 5.3^a

Weight (kg)

78.6 ± 16.8^a

Waist circumference (cm)

99.8 ± 12.0^a

Complications of diabetes

Diabetic nephropathy, n (%)

131 (29.0)

Cataract, n (%)

76 (16.9)

Diabetic retinopathy, n (%)

62 (13.7)

Diabetic neuropathy, n (%)

60 (13.3)

Lifestyle-related diseases

Dyslipidemia, n (%)

294 (65.2)

Hypertension, n (%)

259 (57.4)

Fatty liver, n (%)

218 (48.3)

**Table 2.** Multiple Regression Analysis of the Change of HbA1c in Week 104 (N = 271)
Order	Independent variable	Standardized beta coefficient	Partial regression coefficient	P value
Adjusted R² = 0.425. Dependent variable: change of HbA1c (week 104 - baseline). Independent variables: sex (0: male, 1: female), age, duration of diabetes, baseline HbA1c, and baseline BMI. BMI: body mass index; HbA1c: hemoglobin A1c.
	Fixed number	0	2.835	< 0.0001
1	Baseline HbA1c	-0.646	-0.583	< 0.0001
2	Baseline BMI	0.13	0.033	< 0.0088
3	Duration of diabetes	0.124	0.021	0.0118
4	Sex (0: male, 1: female)	0.08	0.21	0.0874
5	Age	-0.034	-0.004	0.5197

Table 2. Multiple Regression Analysis of the Change of HbA1c in Week 104 (N = 271)

Order

Independent variable

Standardized beta coefficient

Partial regression coefficient

P value

Adjusted R² = 0.425. Dependent variable: change of HbA1c (week 104 - baseline). Independent variables: sex (0: male, 1: female), age, duration of diabetes, baseline HbA1c, and baseline BMI. BMI: body mass index; HbA1c: hemoglobin A1c.

Fixed number

2.835

< 0.0001

Baseline HbA1c

-0.646

-0.583

< 0.0001

Baseline BMI

0.13

0.033

< 0.0088

Duration of diabetes

0.124

0.021

0.0118

Sex (0: male, 1: female)

0.08

0.21

0.0874

Age

-0.034

-0.004

0.5197

**Table 3.** Summary of AEs and ARs
	Number of patients	Incidence (%)
AEs
AEs in all patients (n = 451)	129	28.6
AEs requiring hospitalization	10	2.2
ARs
ARs in all patients (n = 451)	77	17.1
ARs in patients < 65 years old (n = 348)	50	14.4
ARs in patients ≥ 65 years old (n = 103)	27	26.2

Table 3. Summary of AEs and ARs

Number of patients

Incidence (%)

AEs

AEs in all patients (n = 451)

129

28.6

AEs requiring hospitalization

2.2

ARs

ARs in all patients (n = 451)

17.1

ARs in patients < 65 years old (n = 348)

14.4

ARs in patients ≥ 65 years old (n = 103)

26.2

**Table 4.** Serious AEs for Which a Causal Relationship With Ipragliflozin Could Not Be Excluded
AE term	Number of patients	AE term	Number of patients
^aPatients aged ≥ 65 years. AE: adverse event; AR: adverse reaction.
Pyelitis^a	1	Ketosis^a	1
Urinary tract infection^a	1	Dehydration^a	1
Angina unstable	1	Ureterolithiasis^a	1
Nausea^a	1	Depressive symptoms	1
Lung cancer^a	1	-	-

Table 4. Serious AEs for Which a Causal Relationship With Ipragliflozin Could Not Be Excluded

AE term

Number of patients

AE term

Number of patients

^aPatients aged ≥ 65 years. AE: adverse event; AR: adverse reaction.

Pyelitis^a

Ketosis^a

Urinary tract infection^a

Dehydration^a

Angina unstable

Ureterolithiasis^a

Nausea^a

Depressive symptoms

Lung cancer^a