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 https://jocmr.elmerjournals.com

Original Article

Volume 17, Number 6, June 2025, pages 320-333

The Long-Term Effects of the Selective Inhibitor of Urate Transporter 1, Dotinurad, on Metabolic Parameters and Renal Function in Japanese Patients With Asymptomatic Hyperuricemia

↓ Figure 1. Changes in serum uric acid (UA) as compared with baseline by each dose of dotinurad. Black, blue, and red circles and error bars indicate the mean ± standard error of reduced values in serum UA among patients who had taken daily 0.5, 1.0, and 2.0 mg of dotinurad, respectively. *P < 0.05 vs. patients who had taken daily 0.5 and 1.0 mg of dotinurad.

↓ Figure 2. Changes in the hepatic steatosis index after starting dotinurad in all patients (a), patients naive to uric acid (UA)-lowering drugs (b), and patients who switched from xanthine oxidase (XO) inhibitors (c). *P < 0.05 vs. baseline. Circles and error bars indicate the mean ± standard error.

↓ Figure 3. Correlations between serum uric acid (UA) levels and estimated glomerular filtration rate (eGFR) at baseline (a) and 24 months after starting dotinurad (b).

↓ Figure 4. Correlations between urine uric acid (UA) levels and estimated glomerular filtration rate (eGFR) at baseline (a) and 24 months after starting dotinurad (b).

↓ Figure 5. Changes in estimated glomerular filtration rate (eGFR) after 6, 12, 18, and 24 months from baseline in all patients (a), patients naive to uric acid (UA)-lowering drugs (b), and patients who switched from xanthine oxidase (XO) inhibitors (c). We set the baseline data of each patient as 100% and evaluated the changes in eGFR as percent changes in each observation period. *P < 0.05 vs. baseline. Circles and error bars indicate the mean ± standard error.

↓ **Table 1.** Clinical and Laboratory Characteristics of Patients Studied at Baseline (n = 73)
Clinical characteristics
Presented values indicate mean ± SD. ALT: alanine aminotransferase; AST: aspartate aminotransferase; GGT: gamma-glutamyl transferase; eGFR: estimated glomerular filtration rate; HbA1c: hemoglobin A1c; HDL-C: high-density lipoprotein-cholesterol; LDL-C: low-density lipoprotein-cholesterol; Non-HDL-C: non-high-density lipoprotein-cholesterol; TG: triglyceride; UA: uric acid.
Gender (male/female)	50/23
Age (years)	66.1 ± 14.6
Body height (cm)	162.7 ± 19.9
Body weight (kg)	76.7 ± 17.4
Body mass index (kg/m²)	28.3 ± 5.5
Patients with body mass index ≥ 25 kg/m² (n, %)	48, 65.8%
Systolic blood pressure (mm Hg)	133.8 ± 20.1
Diastolic blood pressure (mm Hg)	76.6 ± 12.4
Comorbidities
Type 2 diabetes	48, 65.8%
Hypertension	40, 54.8%
Dyslipidemia	44, 60.3%
Chronic kidney disease	50, 70.4%
Laboratory characteristics	Data at baseline	Normal range
Serum UA (mg/dL)	6.8 ± 1.6	< 7
AST (IU/L)	25.9 ± 9.7	13 - 30
ALT (IU/L)	28.2 ± 19.6	Male 10 - 42; Female 7 - 23
GGT (IU/L)	50.6 ± 49.0	Male 13 - 64; Female 9 - 32
HDL-C (mg/dL)	53.7 ± 15.6	< 40
LDL-C (mg/dL)	100.1 ± 26.8	< 140
TG (mg/dL)	182.6 ± 126.2	Non-fasting value < 175
Non-HDL-C (mg/dL)	130.9 ± 29.7	< 170
HbA1c (%)	6.7 ± 1.6	4.9 - 6.0
eGFR (mL/min/1.73 m²)	61.2 ± 20.4	< 60

↓ Table 1. Clinical and Laboratory Characteristics of Patients Studied at Baseline (n = 73)

Clinical characteristics

Presented values indicate mean ± SD. ALT: alanine aminotransferase; AST: aspartate aminotransferase; GGT: gamma-glutamyl transferase; eGFR: estimated glomerular filtration rate; HbA1c: hemoglobin A1c; HDL-C: high-density lipoprotein-cholesterol; LDL-C: low-density lipoprotein-cholesterol; Non-HDL-C: non-high-density lipoprotein-cholesterol; TG: triglyceride; UA: uric acid.

Gender (male/female)

50/23

Age (years)

66.1 ± 14.6

Body height (cm)

162.7 ± 19.9

Body weight (kg)

76.7 ± 17.4

Body mass index (kg/m²)

28.3 ± 5.5

Patients with body mass index ≥ 25 kg/m² (n, %)

48, 65.8%

Systolic blood pressure (mm Hg)

133.8 ± 20.1

Diastolic blood pressure (mm Hg)

76.6 ± 12.4

Comorbidities

Type 2 diabetes

48, 65.8%

Hypertension

40, 54.8%

Dyslipidemia

44, 60.3%

Chronic kidney disease

50, 70.4%

Laboratory characteristics

Data at baseline

Normal range

Serum UA (mg/dL)

6.8 ± 1.6

< 7

AST (IU/L)

25.9 ± 9.7

13 - 30

ALT (IU/L)

28.2 ± 19.6

Male 10 - 42; Female 7 - 23

GGT (IU/L)

50.6 ± 49.0

Male 13 - 64; Female 9 - 32

HDL-C (mg/dL)

53.7 ± 15.6

< 40

LDL-C (mg/dL)

100.1 ± 26.8

< 140

TG (mg/dL)

182.6 ± 126.2

Non-fasting value < 175

Non-HDL-C (mg/dL)

130.9 ± 29.7

< 170

HbA1c (%)

6.7 ± 1.6

4.9 - 6.0

eGFR (mL/min/1.73 m²)

61.2 ± 20.4

< 60

↓ **Table 2.** Drugs Used for Hyperuricemia Prior to the Initiation of Dotinurad, and Drugs for Type 2 Diabetes, Hypertension, Dyslipidemia, and Daily Doses of Dotinurad at 24 Months
	n
For hyperuricemia
Febuxostat	26
Topiroxostat	3
Allopurinol	6
For type 2 diabetes
Glucagon-like peptide-1 receptor agonists	18
Sodium glucose co-transporter 2 inhibitors	31
Metformin	22
Dipeptidyl peptidase 4 inhibitors	20
Sulfonylurea	3
Insulin	7
Pioglitazone	7
For hypertension
Angiotensin II receptor blockers	30
Calcium channel blockers	39
For dyslipidemia
Statins	49
Peroxisome proliferator-activated receptor alpha agonists	17
Daily doses of dotinurad
0.5 mg	23
1.0 mg	28
2.0 mg	20
4.0 mg	2

↓ Table 2. Drugs Used for Hyperuricemia Prior to the Initiation of Dotinurad, and Drugs for Type 2 Diabetes, Hypertension, Dyslipidemia, and Daily Doses of Dotinurad at 24 Months

For hyperuricemia

Febuxostat

Topiroxostat

Allopurinol

For type 2 diabetes

Glucagon-like peptide-1 receptor agonists

Sodium glucose co-transporter 2 inhibitors

Metformin

Dipeptidyl peptidase 4 inhibitors

Sulfonylurea

Insulin

Pioglitazone

For hypertension

Angiotensin II receptor blockers

Calcium channel blockers

For dyslipidemia

Statins

Peroxisome proliferator-activated receptor alpha agonists

Daily doses of dotinurad

0.5 mg

1.0 mg

2.0 mg

4.0 mg

↓ **Table 3.** Changes in Metabolic Parameters at 6, 12, 18, and 24 Months After Starting Dotinurad in All Patients
	N	Baseline	After 6 months	N	Baseline	After 12 months	N	Baseline	After 18 months	N	Baseline	After 24 months
Presented values indicate mean ± SD. *P < 0.05 vs. baseline values. ALT: alanine aminotransferase; AST: aspartate aminotransferase; BP: blood pressure; eGFR: estimated glomerular filtration rate; GGT: gamma-glutamyl transferase; HbA1c: hemoglobin A1c; HDL-C: high-density lipoprotein-cholesterol; LDL-C: low-density lipoprotein-cholesterol; Non-HDL-C: non-high-density lipoprotein-cholesterol; TG: triglyceride; UA: uric acid; UACR: urine albumin/creatinine ratio.
Body weight (kg)	65	76.2 ± 17.0	75.2 ± 16.3	64	75.8 ± 17.2	75.2 ± 17.1	65	76.4 ± 17.6	75.9 ± 18.0	64	76.3 ± 17.7	75.0 ± 18.0*
Systolic BP (mm Hg)	67	133.0 ± 19.8	132.5 ± 13.8	66	132.8 ± 19.9	131.3 ± 16.4	65	132.2 ± 19.3	130.6 ± 14.0	65	133.1 ± 20.2	127.9 ± 13.9
Diastolic BP (mm Hg)	67	76.4 ± 12.6	76.8 ± 11.0	66	76.1 ± 12.5	74.1 ± 12.5	66	76.3 ± 12.7	75.9 ± 13.0	65	76.2 ± 12.7	73.5 ± 12.8
Serum UA (mg/dL)	70	6.7 ± 1.6	5.8 ± 1.2*	71	6.8 ± 1.6	5.7 ± 1.0*	71	6.8 ± 1.6	5.5 ± 1.2*	69	6.7 ± 1.6	5.5 ± 1.4*
Urine UA (/creatinine)	45	0.34 ± 0.16	0.46 ± 0.26*	47	0.35 ± 0.17	0.44 ± 0.24*	45	0.36 ± 0.17	0.46 ± 0.20*	44	0.35 ± 0.17	0.52 ± 0.23*
HbA1c (%)	65	6.7 ± 1.1	6.7 ± 0.9	67	6.7 ± 1.1	6.7 ± 0.9	67	6.7 ± 1.1	6.7 ± 0.9	64	6.7 ± 1.1	6.7 ± 0.9
AST (IU/L)	70	26.1 ± 9.9	25.0 ± 10.1	71	26.0 ± 9.9	25.1 ± 9.9	71	26.0 ± 9.9	26.5 ± 14.3	69	25.6 ± 9.1	25.1 ± 8.4
ALT (IU/L)	70	28.3 ± 19.9	26.1 ± 20.0	71	28.2 ± 19.8	25.3 ± 15.9*	71	28.2 ± 19.8	27.1 ± 22.7	69	27.9 ± 20.0	24.6 ± 13.5
GGT (IU/L)	66	51.3 ± 50.0	50.0 ± 61.2	68	51.0 ± 49.2	44.0 ± 48.4*	68	51.0 ± 49.2	44.7 ± 56.6*	66	48.8 ± 47.1	39.7 ± 29.7*
TG (mg/dL)	70	182.6 ± 128.3	155.9 ± 87.3	71	183.6 ± 127.7	161.7 ± 103.9	71	183.6 ± 127.7	158.9 ± 90.5	68	183.3 ± 130.5	159.1 ± 126.5*
HDL-C (mg/dL)	70	53.8 ± 15.6	56.6 ± 15.9	71	53.7 ± 15.8	53.4 ± 15.9	71	53.7 ± 15.8	54.5 ± 15.7	68	53.2 ± 15.3	52.7 ± 14.1
LDL-C (mg/dL)	63	98.9 ± 26.5	99.8 ± 25.3	63	98.9 ± 26.5	95.9 ± 23.0	64	99.5 ± 26.7	95.7 ± 26.3	61	99.7 ± 26.1	94.7 ± 24.7
Non-HDL-C (mg/dL)	61	130.0 ± 29.7	122.9 ± 27.8	61	130.6 ± 30.6	119.8 ± 24.8*	61	130.6 ± 30.6	119.1 ± 25.3*	59	131.7 ± 30.4	120.3 ± 25.6*
eGFR (mL/min/1.73 m²)	70	61.0 ± 18.8	59.2 ± 17.5	71	60.4 ± 19.2	58.2 ± 17.7*	71	60.4 ± 19.2	57.1 ± 16.7*	69	59.9 ± 18.8	56.2 ± 18.0*
UACR (/creatinine)	40	227.4 ± 438.3	119.3 ± 323.0*	43	300.7 ± 542.4	335.0 ± 685.2	42	259.7 ± 473.9	202.6 ± 401.3	38	267.1 ± 489.8	172.2 ± 438.6*

↓ Table 3. Changes in Metabolic Parameters at 6, 12, 18, and 24 Months After Starting Dotinurad in All Patients

Baseline

After 6 months

Baseline

After 12 months

Baseline

After 18 months

Baseline

After 24 months

Presented values indicate mean ± SD. *P < 0.05 vs. baseline values. ALT: alanine aminotransferase; AST: aspartate aminotransferase; BP: blood pressure; eGFR: estimated glomerular filtration rate; GGT: gamma-glutamyl transferase; HbA1c: hemoglobin A1c; HDL-C: high-density lipoprotein-cholesterol; LDL-C: low-density lipoprotein-cholesterol; Non-HDL-C: non-high-density lipoprotein-cholesterol; TG: triglyceride; UA: uric acid; UACR: urine albumin/creatinine ratio.

Body weight (kg)

76.2 ± 17.0

75.2 ± 16.3

75.8 ± 17.2

75.2 ± 17.1

76.4 ± 17.6

75.9 ± 18.0

76.3 ± 17.7

75.0 ± 18.0*

Systolic BP (mm Hg)

133.0 ± 19.8

132.5 ± 13.8

132.8 ± 19.9

131.3 ± 16.4

132.2 ± 19.3

130.6 ± 14.0

133.1 ± 20.2

127.9 ± 13.9

Diastolic BP (mm Hg)

76.4 ± 12.6

76.8 ± 11.0

76.1 ± 12.5

74.1 ± 12.5

76.3 ± 12.7

75.9 ± 13.0

76.2 ± 12.7

73.5 ± 12.8

Serum UA (mg/dL)

6.7 ± 1.6

5.8 ± 1.2*

6.8 ± 1.6

5.7 ± 1.0*

6.8 ± 1.6

5.5 ± 1.2*

6.7 ± 1.6

5.5 ± 1.4*

Urine UA (/creatinine)

0.34 ± 0.16

0.46 ± 0.26*

0.35 ± 0.17

0.44 ± 0.24*

0.36 ± 0.17

0.46 ± 0.20*

0.35 ± 0.17

0.52 ± 0.23*

HbA1c (%)

6.7 ± 1.1

6.7 ± 0.9

6.7 ± 1.1

6.7 ± 0.9

6.7 ± 1.1

6.7 ± 0.9

6.7 ± 1.1

6.7 ± 0.9

AST (IU/L)

26.1 ± 9.9

25.0 ± 10.1

26.0 ± 9.9

25.1 ± 9.9

26.0 ± 9.9

26.5 ± 14.3

25.6 ± 9.1

25.1 ± 8.4

ALT (IU/L)

28.3 ± 19.9

26.1 ± 20.0

28.2 ± 19.8

25.3 ± 15.9*

28.2 ± 19.8

27.1 ± 22.7

27.9 ± 20.0

24.6 ± 13.5

GGT (IU/L)

51.3 ± 50.0

50.0 ± 61.2

51.0 ± 49.2

44.0 ± 48.4*

51.0 ± 49.2

44.7 ± 56.6*

48.8 ± 47.1

39.7 ± 29.7*

TG (mg/dL)

182.6 ± 128.3

155.9 ± 87.3

183.6 ± 127.7

161.7 ± 103.9

183.6 ± 127.7

158.9 ± 90.5

183.3 ± 130.5

159.1 ± 126.5*

HDL-C (mg/dL)

53.8 ± 15.6

56.6 ± 15.9

53.7 ± 15.8

53.4 ± 15.9

53.7 ± 15.8

54.5 ± 15.7

53.2 ± 15.3

52.7 ± 14.1

LDL-C (mg/dL)

98.9 ± 26.5

99.8 ± 25.3

98.9 ± 26.5

95.9 ± 23.0

99.5 ± 26.7

95.7 ± 26.3

99.7 ± 26.1

94.7 ± 24.7

Non-HDL-C (mg/dL)

130.0 ± 29.7

122.9 ± 27.8

130.6 ± 30.6

119.8 ± 24.8*

130.6 ± 30.6

119.1 ± 25.3*

131.7 ± 30.4

120.3 ± 25.6*

eGFR (mL/min/1.73 m²)

61.0 ± 18.8

59.2 ± 17.5

60.4 ± 19.2

58.2 ± 17.7*

60.4 ± 19.2

57.1 ± 16.7*

59.9 ± 18.8

56.2 ± 18.0*

UACR (/creatinine)

227.4 ± 438.3

119.3 ± 323.0*

300.7 ± 542.4

335.0 ± 685.2

259.7 ± 473.9

202.6 ± 401.3

267.1 ± 489.8

172.2 ± 438.6*

↓ **Table 4.** Changes in Metabolic Parameters at 6, 12, 18, and 24 Months After Starting Dotinurad in Patients Naive to UA-Lowering Drugs
	N	Baseline	After 6 months	N	Baseline	After 12 months	N	Baseline	After 18 months	N	Baseline	After 24 months
Presented values indicate mean ± SD. *P < 0.05 vs. baseline values. ALT: alanine aminotransferase; AST: aspartate aminotransferase; BP: blood pressure; eGFR: estimated glomerular filtration rate; GGT: gamma-glutamyl transferase; HbA1c: hemoglobin A1c; HDL-C: high-density lipoprotein-cholesterol; LDL-C: low-density lipoprotein-cholesterol; Non-HDL-C: non-high-density lipoprotein-cholesterol; TG: triglyceride; UA: uric acid; UACR: urine albumin/creatinine ratio.
Body weight (kg)	35	71.9 ± 17.0	71.1 ± 16.2	35	71.6 ± 17.3	71.2 ± 17.1	35	71.6 ± 17.3	71.3 ± 17.6	33	70.9 ± 17.5	69.5 ± 17.6
Systolic BP (mm Hg)	36	133.3 ± 20.2	133.9 ± 15.0	36	133.4 ± 20.4	131.8 ± 16.4	35	132.1 ± 19.1	130.5 ± 14.5	34	133.5 ± 21.0	127.9 ± 12.9
Diastolic BP (mm Hg)	36	75.9 ± 13.6	77.4 ± 11.4	36	75.6 ± 13.5	73.4 ± 12.8	35	75.5 ± 13.6	76.5 ± 12.3	34	75.5 ± 13.8	72.3 ± 11.1
Serum UA (mg/dL)	37	7.7 ± 1.4	5.8 ± 1.1*	38	7.7 ± 1.4	5.8 ± 0.9*	38	7.7 ± 1.4	5.5 ± 1.2*	36	7.7 ± 1.4	5.6 ± 1.5*
Urine UA (/creatinine)	20	0.41 ± 0.18	0.45 ± 0.23	22	0.43 ± 0.19	0.42 ± 0.22	22	0.43 ± 0.19	0.42 ± 0.21	20	0.44 ± 0.20	0.52 ± 0.23
HbA1c (%)	35	6.8 ± 1.2	6.8 ± 0.9	36	6.8 ± 1.2	6.7 ± 0.8	36	6.8 ± 1.2	6.8 ± 0.9	34	6.9 ± 1.2	6.9 ± 0.8
AST (IU/L)	37	25.2 ± 8.6	24.6 ± 8.1	38	25.0 ± 8.5	23.9 ± 7.8	38	25.0 ± 8.5	25.1 ± 12.6	36	24.2 ± 6.6	24.1 ± 7.2
ALT (IU/L)	37	25.7 ± 16.7	22.9 ± 11.4	38	25.5 ± 16.5	22.3 ± 11.8	38	25.5 ± 16.5	24.1 ± 15.2	36	24.8 ± 16.7	22.4 ± 12.0
GGT (IU/L)	37	45.0 ± 36.8	41.4 ± 31.4	38	44.6 ± 36.3	38.9 ± 38.1	38	44.6 ± 36.3	35.4 ± 22.3	36	40.3 ± 28.6	34.7 ± 19.1
TG (mg/dL)	37	192.2 ± 157.3	162.2 ± 96.7	38	194.0 ± 155.5	174.0 ± 126.1	38	194.0 ± 155.5	166.4 ± 92.6	36	193.4 ± 160.0	180.6 ± 157.0
HDL-C (mg/dL)	37	51.3 ± 15.8	54.9 ± 17.0	38	51.1 ± 15.6	48.6 ± 12.0	38	51.1 ± 15.6	51.5 ± 13.0	36	50.8 ± 15.1	48.8 ± 12.9
LDL-C (mg/dL)	37	105.1 ± 32.0	101.5 ± 24.0	38	105.9 ± 32.0	96.7 ± 21.7*	38	105.9 ± 32.0	96.4 ± 26.1	36	105.6 ± 31.7	96.4 ± 28.3
Non-HDL-C (mg/dL)	37	122.6 ± 39.4	112.0 ± 37.0	38	124.3 ± 40.2	108.6 ± 34.9*	38	124.3 ± 40.2	107.6 ± 34.0*	36	127.1 ± 38.4	113.1 ± 32.4
eGFR (mL/min/1.73 m²)	37	58.6 ± 17.9	55.8 ± 14.1	38	57.6 ± 18.6	55.0 ± 16.0	38	57.6 ± 18.6	53.9 ± 14.5	36	56.4 ± 17.5	51.4 ± 14.7*
UACR (/creatinine)	21	276.1 ± 471.7	181.3 ± 435.5	26	323.7 ± 584.1	338.1 ± 649.2	24	269.2 ± 484.2	195.0 ± 397.0	23	252.9 ± 486.7	125.9 ± 256.8*

↓ Table 4. Changes in Metabolic Parameters at 6, 12, 18, and 24 Months After Starting Dotinurad in Patients Naive to UA-Lowering Drugs

Baseline

After 6 months

Baseline

After 12 months

Baseline

After 18 months

Baseline

After 24 months

Body weight (kg)

71.9 ± 17.0

71.1 ± 16.2

71.6 ± 17.3

71.2 ± 17.1

71.6 ± 17.3

71.3 ± 17.6

70.9 ± 17.5

69.5 ± 17.6

Systolic BP (mm Hg)

133.3 ± 20.2

133.9 ± 15.0

133.4 ± 20.4

131.8 ± 16.4

132.1 ± 19.1

130.5 ± 14.5

133.5 ± 21.0

127.9 ± 12.9

Diastolic BP (mm Hg)

75.9 ± 13.6

77.4 ± 11.4

75.6 ± 13.5

73.4 ± 12.8

75.5 ± 13.6

76.5 ± 12.3

75.5 ± 13.8

72.3 ± 11.1

Serum UA (mg/dL)

7.7 ± 1.4

5.8 ± 1.1*

7.7 ± 1.4

5.8 ± 0.9*

7.7 ± 1.4

5.5 ± 1.2*

7.7 ± 1.4

5.6 ± 1.5*

Urine UA (/creatinine)

0.41 ± 0.18

0.45 ± 0.23

0.43 ± 0.19

0.42 ± 0.22

0.43 ± 0.19

0.42 ± 0.21

0.44 ± 0.20

0.52 ± 0.23

HbA1c (%)

6.8 ± 1.2

6.8 ± 0.9

6.8 ± 1.2

6.7 ± 0.8

6.8 ± 1.2

6.8 ± 0.9

6.9 ± 1.2

6.9 ± 0.8

AST (IU/L)

25.2 ± 8.6

24.6 ± 8.1

25.0 ± 8.5

23.9 ± 7.8

25.0 ± 8.5

25.1 ± 12.6

24.2 ± 6.6

24.1 ± 7.2

ALT (IU/L)

25.7 ± 16.7

22.9 ± 11.4

25.5 ± 16.5

22.3 ± 11.8

25.5 ± 16.5

24.1 ± 15.2

24.8 ± 16.7

22.4 ± 12.0

GGT (IU/L)

45.0 ± 36.8

41.4 ± 31.4

44.6 ± 36.3

38.9 ± 38.1

44.6 ± 36.3

35.4 ± 22.3

40.3 ± 28.6

34.7 ± 19.1

TG (mg/dL)

192.2 ± 157.3

162.2 ± 96.7

194.0 ± 155.5

174.0 ± 126.1

194.0 ± 155.5

166.4 ± 92.6

193.4 ± 160.0

180.6 ± 157.0

HDL-C (mg/dL)

51.3 ± 15.8

54.9 ± 17.0

51.1 ± 15.6

48.6 ± 12.0

51.1 ± 15.6

51.5 ± 13.0

50.8 ± 15.1

48.8 ± 12.9

LDL-C (mg/dL)

105.1 ± 32.0

101.5 ± 24.0

105.9 ± 32.0

96.7 ± 21.7*

105.9 ± 32.0

96.4 ± 26.1

105.6 ± 31.7

96.4 ± 28.3

Non-HDL-C (mg/dL)

122.6 ± 39.4

112.0 ± 37.0

124.3 ± 40.2

108.6 ± 34.9*

124.3 ± 40.2

107.6 ± 34.0*

127.1 ± 38.4

113.1 ± 32.4

eGFR (mL/min/1.73 m²)

58.6 ± 17.9

55.8 ± 14.1

57.6 ± 18.6

55.0 ± 16.0

57.6 ± 18.6

53.9 ± 14.5

56.4 ± 17.5

51.4 ± 14.7*

UACR (/creatinine)

276.1 ± 471.7

181.3 ± 435.5

323.7 ± 584.1

338.1 ± 649.2

269.2 ± 484.2

195.0 ± 397.0

252.9 ± 486.7

125.9 ± 256.8*

↓ **Table 5.** Changes in Metabolic Parameters at 6, 12, 18, and 24 Months After Starting Dotinurad in Patients Who Switched From XO Inhibitors
	N	Baseline	After 6 months	N	Baseline	After 12 months	N	Baseline	After 18 months	N	Baseline	After 24 months
Presented values indicate mean ± SD. *P < 0.05 vs. baseline values. ALT: alanine aminotransferase; AST: aspartate aminotransferase; BP: blood pressure; eGFR: estimated glomerular filtration rate; GGT: gamma-glutamyl transferase; HbA1c: hemoglobin A1c; HDL-C: high-density lipoprotein-cholesterol; LDL-C: low-density lipoprotein-cholesterol; Non-HDL-C: non-high-density lipoprotein-cholesterol; TG: triglyceride; UA: uric acid; UACR: urine albumin/creatinine ratio; XO: xanthine oxidase.
Body weight (kg)	30	81.3 ± 15.9	80.1 ± 15.2	29	80.8 ± 16.0	80.0 ± 16.1	30	82.0 ± 16.5	81.3 ± 17.1	31	82.0 ± 16.2	80.8 ± 16.6
Systolic BP (mm Hg)	31	132.7 ± 19.6	130.8 ± 12.3	30	132.1 ± 19.6	130.7 ± 16.5	30	132.3 ± 19.8	130.6 ± 13.5	31	132.7 ± 19.6	127.8 ± 15.1
Diastolic BP (mm Hg)	31	77.1 ± 11.5	76.2 ± 10.7	30	76.7 ± 11.4	75.0 ± 12.4	30	77.2 ± 11.7	75.3 ± 14.0	31	77.1 ± 11.5	74.8 ± 15.0
Serum UA (mg/dL)	33	5.7 ± 1.2	5.8 ± 1.3	33	5.7 ± 1.2	5.6 ± 1.2	33	5.7 ± 1.2	5.5 ± 1.4	33	5.7 ± 1.2	5.5 ± 1.3
Urine UA (/creatinine)	25	0.28 ± 0.11	0.47 ± 0.28*	25	0.28 ± 0.11	0.47 ± 0.27*	23	0.28 ± 0.12	0.49 ± 0.19*	24	0.28 ± 0.11	0.53 ± 0.23*
HbA1c (%)	30	6.5 ± 1.0	6.6 ± 1.0	31	6.5 ± 1.0	6.6 ± 0.9*	31	6.5 ± 1.0	6.6 ± 1.0	30	6.5 ± 1.0	6.6 ± 0.8
AST (IU/L)	33	27.0 ± 11.2	25.5 ± 12.1	33	27.0 ± 11.2	26.5 ± 11.8	33	27.0 ± 11.2	28.2 ± 16.0	33	27.0 ± 11.2	26.2 ± 9.4
ALT (IU/L)	33	31.2 ± 22.8	29.6 ± 26.3	33	31.2 ± 28.7	28.7 ± 19.2	33	31.2 ± 22.8	30.7 ± 29.0	33	31.2 ± 22.8	27.0 ± 14.9
GGT (IU/L)	29	59.3 ± 62.7	60.9 ± 84.9	30	59.0 ± 61.6	50.4 ± 59.0*	30	59.0 ± 61.6	56.6 ± 80.6	30	59.0 ± 61.6	45.6 ± 38.3*
TG (mg/dL)	33	171.8 ± 86.2	148.8 ± 76.2	33	171.8 ± 86.2	147.5 ± 69.5	33	171.8 ± 86.2	150.2 ± 88.6	32	171.8 ± 87.6	135.0 ± 75.1*
HDL-C (mg/dL)	33	56.7 ± 15.7	58.5 ± 14.7	33	56.7 ± 15.7	59.0 ± 18.2	33	56.7 ± 15.7	58.1 ± 17.9	32	55.9 ± 15.2	57.2 ± 14.2
LDL-C (mg/dL)	31	97.5 ± 26.9	100.1 ± 26.8	31	97.5 ± 26.9	97.5 ± 26.1	31	97.5 ± 26.9	95.0 ± 26.6	30	98.6 ± 26.6	96.3 ± 23.9
Non-HDL-C (mg/dL)	30	127.0 ± 26.9	122.9 ± 27.1	30	127.0 ± 26.9	118.2 ± 25.6	30	127.0 ± 26.9	119.4 ± 24.6	29	128.4 ± 27.4	118.3 ± 25.4*
eGFR (mL/min/1.73 m²)	33	63.7 ± 19.8	63.1 ± 20.0	33	63.7 ± 19.8	61.9 ± 19.2	33	63.7 ± 19.8	60.8 ± 18.4*	33	63.7 ± 19.8	61.3 ± 20.0
UACR (/creatinine)	19	173.6 ± 404.0	50.7 ± 76.4*	17	257.9 ± 485.7	330.5 ± 757.5	18	246.9 ± 473.5	212.7 ± 418.4	15	288.8 ± 510.8	243.3 ± 629.1

↓ Table 5. Changes in Metabolic Parameters at 6, 12, 18, and 24 Months After Starting Dotinurad in Patients Who Switched From XO Inhibitors

Baseline

After 6 months

Baseline

After 12 months

Baseline

After 18 months

Baseline

After 24 months

Body weight (kg)

81.3 ± 15.9

80.1 ± 15.2

80.8 ± 16.0

80.0 ± 16.1

82.0 ± 16.5

81.3 ± 17.1

82.0 ± 16.2

80.8 ± 16.6

Systolic BP (mm Hg)

132.7 ± 19.6

130.8 ± 12.3

132.1 ± 19.6

130.7 ± 16.5

132.3 ± 19.8

130.6 ± 13.5

132.7 ± 19.6

127.8 ± 15.1

Diastolic BP (mm Hg)

77.1 ± 11.5

76.2 ± 10.7

76.7 ± 11.4

75.0 ± 12.4

77.2 ± 11.7

75.3 ± 14.0

77.1 ± 11.5

74.8 ± 15.0

Serum UA (mg/dL)

5.7 ± 1.2

5.8 ± 1.3

5.7 ± 1.2

5.6 ± 1.2

5.7 ± 1.2

5.5 ± 1.4

5.7 ± 1.2

5.5 ± 1.3

Urine UA (/creatinine)

0.28 ± 0.11

0.47 ± 0.28*

0.28 ± 0.11

0.47 ± 0.27*

0.28 ± 0.12

0.49 ± 0.19*

0.28 ± 0.11

0.53 ± 0.23*

HbA1c (%)

6.5 ± 1.0

6.6 ± 1.0

6.5 ± 1.0

6.6 ± 0.9*

6.5 ± 1.0

6.6 ± 1.0

6.5 ± 1.0

6.6 ± 0.8

AST (IU/L)

27.0 ± 11.2

25.5 ± 12.1

27.0 ± 11.2

26.5 ± 11.8

27.0 ± 11.2

28.2 ± 16.0

27.0 ± 11.2

26.2 ± 9.4

ALT (IU/L)

31.2 ± 22.8

29.6 ± 26.3

31.2 ± 28.7

28.7 ± 19.2

31.2 ± 22.8

30.7 ± 29.0

31.2 ± 22.8

27.0 ± 14.9

GGT (IU/L)

59.3 ± 62.7

60.9 ± 84.9

59.0 ± 61.6

50.4 ± 59.0*

59.0 ± 61.6

56.6 ± 80.6

59.0 ± 61.6

45.6 ± 38.3*

TG (mg/dL)

171.8 ± 86.2

148.8 ± 76.2

171.8 ± 86.2

147.5 ± 69.5

171.8 ± 86.2

150.2 ± 88.6

171.8 ± 87.6

135.0 ± 75.1*

HDL-C (mg/dL)

56.7 ± 15.7

58.5 ± 14.7

56.7 ± 15.7

59.0 ± 18.2

56.7 ± 15.7

58.1 ± 17.9

55.9 ± 15.2

57.2 ± 14.2

LDL-C (mg/dL)

97.5 ± 26.9

100.1 ± 26.8

97.5 ± 26.9

97.5 ± 26.1

97.5 ± 26.9

95.0 ± 26.6

98.6 ± 26.6

96.3 ± 23.9

Non-HDL-C (mg/dL)

127.0 ± 26.9

122.9 ± 27.1

127.0 ± 26.9

118.2 ± 25.6

127.0 ± 26.9

119.4 ± 24.6

128.4 ± 27.4

118.3 ± 25.4*

eGFR (mL/min/1.73 m²)

63.7 ± 19.8

63.1 ± 20.0

63.7 ± 19.8

61.9 ± 19.2

63.7 ± 19.8

60.8 ± 18.4*

63.7 ± 19.8

61.3 ± 20.0

UACR (/creatinine)

173.6 ± 404.0

50.7 ± 76.4*

257.9 ± 485.7

330.5 ± 757.5

246.9 ± 473.5

212.7 ± 418.4

288.8 ± 510.8

243.3 ± 629.1