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