Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

Journal website https://cr.elmerpub.com

Original Article

Volume 16, Number 6, December 2025, pages 489-498

Anti-Oxidative Effect of Dapagliflozin, a Selective Sodium Glucose Transporter-2 Inhibitor, for Cardio-Renal Protection in Patients With Heart Failure With Reduced Ejection Fraction

Figure 1. Changes in serum markers of fibrosis after treatment with dapagliflozin for 6 months. Changes in galectin-3 (a), PIIINP (b), PiCP (c), and endotrophin (d) before and after treatment with dapagliflozin. *Significant differences between before and after treatment. PIIINP: procollagen type III N-terminal propeptide; PiCP: procollagen type I C-terminal propeptide; NS: not significant.

Figure 2. Changes in serum markers of antioxidative effects after treatment with dapagliflozin for 6 months. Changes in myeloperoxidase (a), MMP-1 (b), MMP-2 (c), and MMP-9 (d) between before and after treatment with dapagliflozin. *Significant differences between before and after treatment. MMP-1: matrix metalloproteinase-1; MMP-2: matrix metalloproteinase-2; MMP-9: matrix metalloproteinase-9; NS: not significant.

Figure 3. Changes in serum age-related proteins after treatment with dapagliflozin for 6 months. Changes in α-Klotho (a), FGF-21 (b), and GDF-11 (c) between before and after treatment with dapagliflozin. *Significant differences between before and after treatment. FGF-21: fibroblast growth factor-21; GDF-11: growth differentiation factor-11; NS: not significant.

**Table 1.** Baseline Characteristics (n = 25)
Characteristics
Continuous variables are expressed as mean ± SD. AF: atrial fibrillation; CKD: chronic kidney disease; IHD: ischemic heart disease.
Age, years	67.0 ± 13.6
Male, n (%)	16 (64.0)
Smoking, n (%)	19 (76.0)
Hypertension, n (%)	14 (56.0)
Diabetes mellitus, n (%)	4 (16.0)
Dyslipidemia, n (%)	12 (48.0)
CKD, n (%)	7 (28.0)
Cardiovascular disease
IHD, n (%)	9 (36.0)
Cardiomyopathy, n (%)	6 (24.0)
AF, n (%)	13 (52.0)

Table 1. Baseline Characteristics (n = 25)

Characteristics

Continuous variables are expressed as mean ± SD. AF: atrial fibrillation; CKD: chronic kidney disease; IHD: ischemic heart disease.

Age, years

67.0 ± 13.6

Male, n (%)

16 (64.0)

Smoking, n (%)

19 (76.0)

Hypertension, n (%)

14 (56.0)

Diabetes mellitus, n (%)

4 (16.0)

Dyslipidemia, n (%)

12 (48.0)

CKD, n (%)

7 (28.0)

Cardiovascular disease

IHD, n (%)

9 (36.0)

Cardiomyopathy, n (%)

6 (24.0)

AF, n (%)

13 (52.0)

**Table 2.** Changes in Vital Signs and Medications After Treatment With Dapagliflozin for 6 Months (n = 25)
	Before treatment	After treatment for 6 months	P-value
Continuous variables are expressed as mean ± SD. ACEi/ARB/ARNi: angiotensin-converting-enzyme inhibitor/angiotensin II receptor blocker/angiotensin receptor neprilysin inhibitor; BMI: body mass index; BW: body weight; CCB: calcium channel blocker; DBP: diastolic blood pressure; MRA: mineralocorticoid receptor antagonist; SBP: systolic blood pressure.
BW, kg	63.4 ± 12.4	60.2 ± 11.8	< 0.001
BMI, kg/m²	24.0 ± 4.5	22.3 ± 4.1	< 0.001
SBP, mm Hg	123 ± 24	117 ± 21	0.17
DBP, mm Hg	79.3 ± 15.0	74.7 ± 12.6	0.10
Medications
ARB/ACEi/ARNi, n (%)	16 (64.0)	18 (72.0)	0.31
β-blocker, n (%)	19 (76.0)	20 (80.0)	0.65
MRA, n (%)	15 (60.0)	15 (60.0)	1.0
Pimobendan, n (%)	3 (12.0)	3 (12.0)	1.0
CCB, n (%)	6 (24.0)	5 (20.0)	0.56
Diuretics, n (%)	16 (64.0)	14 (56.0)	0.32
Statin, n (%)	9 (36.0)	10 (40.0)	0.56

Table 2. Changes in Vital Signs and Medications After Treatment With Dapagliflozin for 6 Months (n = 25)

Before treatment

After treatment for 6 months

P-value

Continuous variables are expressed as mean ± SD. ACEi/ARB/ARNi: angiotensin-converting-enzyme inhibitor/angiotensin II receptor blocker/angiotensin receptor neprilysin inhibitor; BMI: body mass index; BW: body weight; CCB: calcium channel blocker; DBP: diastolic blood pressure; MRA: mineralocorticoid receptor antagonist; SBP: systolic blood pressure.

BW, kg

63.4 ± 12.4

60.2 ± 11.8

< 0.001

BMI, kg/m²

24.0 ± 4.5

22.3 ± 4.1

< 0.001

SBP, mm Hg

123 ± 24

117 ± 21

0.17

DBP, mm Hg

79.3 ± 15.0

74.7 ± 12.6

0.10

Medications

ARB/ACEi/ARNi, n (%)

16 (64.0)

18 (72.0)

0.31

β-blocker, n (%)

19 (76.0)

20 (80.0)

0.65

MRA, n (%)

15 (60.0)

1.0

Pimobendan, n (%)

3 (12.0)

1.0

CCB, n (%)

6 (24.0)

5 (20.0)

0.56

Diuretics, n (%)

16 (64.0)

14 (56.0)

0.32

Statin, n (%)

9 (36.0)

10 (40.0)

0.56

**Table 3.** Changes in the Results of Biochemical Examinations
	Before treatment	After treatment for 6 months	P-value
Continuous variables are expressed as mean ± SD if they are parametric, and as median (interquartile range) if they are non-parametric. Alb: albumin; ALT: alanine aminotransferase; AST: aspartate aminotransferase; BNP: B-type natriuretic peptide; BUN: blood urea nitrogen; Cre: creatinine; CRP: C-reactive protein; eGFR: estimated glomerular filtration rate; Hb: hemoglobin; HCT: hematocrit; LDH: lactate dehydrogenase; L-FABP: liver-type fatty acid binding protein; NAG: N-acetyl-β-D-glycosaminidase; Plt: platelet; RBC: red blood cell; TP: total protein; WBC: white blood cell.
Blood findings
WBC, × 10³/µL	6.70 ± 1.83	5.88 ± 1.65	0.01
RBC, × 10⁶/µL	4.34 ± 0.71	4.74 ± 0.62	0.002
Hb, g/dL	13.0 ± 2.2	14.0 ± 1.7	0.003
Plt, × 10³/µL	221 (179 - 262)	228 ± 89	0.95
HCT, %	39.7 ± 6.6	43.3 ± 5.1	< 0.001
TP, g/dL	6.8 ± 0.8	7.2 ± 0.6	0.008
Alb, g/dL	3.8 ± 0.6	4.2 ± 0.3	0.002
AST, U/L	23 (20 - 34)	25.7 ± 9.3	0.14
ALT, U/L	22 (14 - 34)	14 (10-27)	0.03
LDH, U/L	227 (177 - 249)	207 ± 61	0.12
BUN, mg/dL	18.6 ± 7.7	19.2 ± 5.7	0.69
Cre, mg/dL	1.01 (0.85 - 1.07)	1.02 ± 0.22	0.47
eGFR, mL/min/1.73 m²	56.3 ± 17.8	54.4 ± 15.2	0.43
Ferritin, ng/mL	147 ± 108	83 (29 - 154)	0.01
CRP, mg/dL	0.33 (0.05 - 1.67)	0.08 (0.06 - 0.20)	0.04
BNP, pg/mL	280 (169 - 537)	229 ± 171	0.03
Urinary findings
NAG, IU/L	15.1 ± 10.9	5.9 (2.8 - 10.8)	0.03
Cre, mg/dL	121 ± 59	76.2 ± 45.9	0.005
Microalbumin, mg/L	19.5 (6.0 - 52.0)	10 (5 - 28)	0.34
L-FABP, ng/mL	3.23 (1.30 - 6.82)	2.41 ± 2.40	0.13

Table 3. Changes in the Results of Biochemical Examinations

Before treatment

After treatment for 6 months

P-value

Continuous variables are expressed as mean ± SD if they are parametric, and as median (interquartile range) if they are non-parametric. Alb: albumin; ALT: alanine aminotransferase; AST: aspartate aminotransferase; BNP: B-type natriuretic peptide; BUN: blood urea nitrogen; Cre: creatinine; CRP: C-reactive protein; eGFR: estimated glomerular filtration rate; Hb: hemoglobin; HCT: hematocrit; LDH: lactate dehydrogenase; L-FABP: liver-type fatty acid binding protein; NAG: N-acetyl-β-D-glycosaminidase; Plt: platelet; RBC: red blood cell; TP: total protein; WBC: white blood cell.

Blood findings

WBC, × 10³/µL

6.70 ± 1.83

5.88 ± 1.65

0.01

RBC, × 10⁶/µL

4.34 ± 0.71

4.74 ± 0.62

0.002

Hb, g/dL

13.0 ± 2.2

14.0 ± 1.7

0.003

Plt, × 10³/µL

221 (179 - 262)

228 ± 89

0.95

HCT, %

39.7 ± 6.6

43.3 ± 5.1

< 0.001

TP, g/dL

6.8 ± 0.8

7.2 ± 0.6

0.008

Alb, g/dL

3.8 ± 0.6

4.2 ± 0.3

0.002

AST, U/L

23 (20 - 34)

25.7 ± 9.3

0.14

ALT, U/L

22 (14 - 34)

14 (10-27)

0.03

LDH, U/L

227 (177 - 249)

207 ± 61

0.12

BUN, mg/dL

18.6 ± 7.7

19.2 ± 5.7

0.69

Cre, mg/dL

1.01 (0.85 - 1.07)

1.02 ± 0.22

0.47

eGFR, mL/min/1.73 m²

56.3 ± 17.8

54.4 ± 15.2

0.43

Ferritin, ng/mL

147 ± 108

83 (29 - 154)

0.01

CRP, mg/dL

0.33 (0.05 - 1.67)

0.08 (0.06 - 0.20)

0.04

BNP, pg/mL

280 (169 - 537)

229 ± 171

0.03

Urinary findings

NAG, IU/L

15.1 ± 10.9

5.9 (2.8 - 10.8)

0.03

Cre, mg/dL

121 ± 59

76.2 ± 45.9

0.005

Microalbumin, mg/L

19.5 (6.0 - 52.0)

10 (5 - 28)

0.34

L-FABP, ng/mL

3.23 (1.30 - 6.82)

2.41 ± 2.40

0.13

**Table 4.** Changes in Transthoracic Echocardiography Findings
	Baseline	Post-treatment	P value
Continuous variables are expressed as mean ± SD if they are parametric, and as median (interquartile range) if they are non-parametric. AOD: aortic dimension; E/A: ratio of early to late diastolic filling velocities; E/e’: ratio of early diastolic filling velocity to early diastolic mitral annular velocity; IVS: interventricular septum; LAD: left atrial dimension; LVPW: left ventricular posterior wall; LVDd: left ventricular end-diastolic dimension; LVDs: left ventricular end-systolic dimension; LVEDV: left ventricular end-diastolic volume; LVEF: left ventricular ejection fraction; LVESV: left ventricular end-systolic volume; TRPG: tricuspid regurgitation pressure gradient.
LAD, mm	44.4 ± 11.2	43.0 ± 9.1	0.43
AOD, mm	32.1 (29.7 - 33.3)	32.0 ± 3.2	0.44
IVS, mm	9.72 ± 2.51	9.38 ± 2.55	0.35
LVPW, mm	10.6 ± 1.6	10.2 (9.4 - 10.8)	0.37
LVDd, mm	56.3 ± 9.2	53.9 ± 9.4	0.048
LVDs, mm	48.5 ± 10.6	43.7 ± 11.1	0.005
LVEF, %	30.5 ± 11.3	39.9 ± 14.5	0.002
LVEDV, mL	137 ± 58	115 ± 53	0.02
LVESV, mL	98.0 ± 47.8	71.9 ± 46.0	0.009
E/A	1.4 (0.9 - 2.0)	0.7 (0.5 - 0.8)	0.026
E/e’	17.1 (12.2 - 24.0)	12.7 ± 5.3	0.04
TRPG, mm Hg	33.5 ± 23.3	17.5 (13.0 - 31.0)	0.04

Table 4. Changes in Transthoracic Echocardiography Findings

Baseline

Post-treatment

P value

Continuous variables are expressed as mean ± SD if they are parametric, and as median (interquartile range) if they are non-parametric. AOD: aortic dimension; E/A: ratio of early to late diastolic filling velocities; E/e’: ratio of early diastolic filling velocity to early diastolic mitral annular velocity; IVS: interventricular septum; LAD: left atrial dimension; LVPW: left ventricular posterior wall; LVDd: left ventricular end-diastolic dimension; LVDs: left ventricular end-systolic dimension; LVEDV: left ventricular end-diastolic volume; LVEF: left ventricular ejection fraction; LVESV: left ventricular end-systolic volume; TRPG: tricuspid regurgitation pressure gradient.

LAD, mm

44.4 ± 11.2

43.0 ± 9.1

0.43

AOD, mm

32.1 (29.7 - 33.3)

32.0 ± 3.2

0.44

IVS, mm

9.72 ± 2.51

9.38 ± 2.55

0.35

LVPW, mm

10.6 ± 1.6

10.2 (9.4 - 10.8)

0.37

LVDd, mm

56.3 ± 9.2

53.9 ± 9.4

0.048

LVDs, mm

48.5 ± 10.6

43.7 ± 11.1

0.005

LVEF, %

30.5 ± 11.3

39.9 ± 14.5

0.002

LVEDV, mL

137 ± 58

115 ± 53

0.02

LVESV, mL

98.0 ± 47.8

71.9 ± 46.0

0.009

E/A

1.4 (0.9 - 2.0)

0.7 (0.5 - 0.8)

0.026

E/e’

17.1 (12.2 - 24.0)

12.7 ± 5.3

0.04

TRPG, mm Hg

33.5 ± 23.3

17.5 (13.0 - 31.0)

0.04