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 https://jem.elmerpub.com

Original Article

Volume 15, Number 4, October 2025, pages 130-136

Effect of Imeglimin on Microalbuminuria and Serum Vitamin B12 Concentration in Japanese Patients With Type 2 Diabetes

↓ Figure 1. Changes of estimated glomerular filtration rate and urinary albumin creatinine ratio. Data are expressed as mean ± SE. *P < 0.05, **P < 0.01 vs. baseline. eGFR: estimated glomerular filtration rate; UACR: urinary albumin-to-creatinine ratio.

↓ **Table 1.** Baseline Characteristics of Enrolled Patients
Baseline characteristics	N = 21 (14 men/7 women)
Data are expressed as mean ± SE. SE: standard error; BW: body weight; BMI: body mass index; FPG: fasting plasma glucose; HbA1c: glycated hemoglobin; DPP-4: dipeptidyl peptidase-4; α-GI: α-glucosidase inhibitor; SGLT2: sodium-glucose cotransporter 2; GLP-1: glucagon-like peptide-1.
Variables
Age (years)	65.20 ± 2.43
BW (kg)	68.82 ± 1.17
BMI (kg/m²)	25.81 ± 0.70
FPG (mg/dL)	163.05 ± 7.13
HbA1c (%)	8.08 ± 0.12
Medication of anti-diabetic agents usage
No medication, n (%)	3 (14.3)
Insulin, n (%)	1 (4.7)
Metformin, n (%)	8 (38.0)
Sulfonylurea, n (%)	6 (28.6)
DPP-4 inhibitor, n (%)	17 (81.0)
Glinide, n (%)	3 (14.3)
α-GI, n (%)	3 (14.3)
SGLT2 inhibitor, n (%)	8 (38.0)
GLP-1 receptor agonist (oral), n (%)	1 (4.7)
GLP-1 receptor agonist (injection), n (%)	0 (0.0)

↓ Table 1. Baseline Characteristics of Enrolled Patients

Baseline characteristics

N = 21 (14 men/7 women)

Data are expressed as mean ± SE. SE: standard error; BW: body weight; BMI: body mass index; FPG: fasting plasma glucose; HbA1c: glycated hemoglobin; DPP-4: dipeptidyl peptidase-4; α-GI: α-glucosidase inhibitor; SGLT2: sodium-glucose cotransporter 2; GLP-1: glucagon-like peptide-1.

Variables

Age (years)

65.20 ± 2.43

BW (kg)

68.82 ± 1.17

BMI (kg/m²)

25.81 ± 0.70

FPG (mg/dL)

163.05 ± 7.13

HbA1c (%)

8.08 ± 0.12

Medication of anti-diabetic agents usage

No medication, n (%)

3 (14.3)

Insulin, n (%)

1 (4.7)

Metformin, n (%)

8 (38.0)

Sulfonylurea, n (%)

6 (28.6)

DPP-4 inhibitor, n (%)

17 (81.0)

Glinide, n (%)

3 (14.3)

α-GI, n (%)

3 (14.3)

SGLT2 inhibitor, n (%)

8 (38.0)

GLP-1 receptor agonist (oral), n (%)

1 (4.7)

GLP-1 receptor agonist (injection), n (%)

0 (0.0)

↓ **Table 2.** Changes in Metabolic Parameters
	Baseline	Week 12	P vs. baseline	Week 24	P vs. baseline
Data are expressed as mean ± SE. SE: standard error; BW: body weight; BMI: body mass index; FI: fat index; SMI: skeletal muscle index; SBP: systolic blood pressure; DBP: diastolic blood pressure; FPG: fasting plasma glucose; HbA1c: glycated hemoglobin; LDL: low-density lipoprotein; HDL: high-density lipoprotein; AST: aspartate aminotransferase; ALT: alanine aminotransferase; γ-GTP: γ-glutamyltransferase.
BW (kg)	69.02 ± 2.11	68.69 ± 2.05	0.481	68.74 ± 2.00	0.587
BMI (kg/m²)	25.81 ± 0.70	25.67 ± 0.66	0.408	25.70 ± 0.66	0.563
FI (kg/m²)	7.78 ± 0.76	7.56 ± 0.71	0.145	7.81 ± 0.73	0.960
SMI (kg/m²)	7.90 ± 0.17	8.00 ± 0.19	0.240	7.83 ± 0.19	0.272
SBP (mm Hg)	134.76 ± 2.53	135.19 ± 2.90	0.975	134.00 ± 2.69	0.925
DBP (mm Hg)	77.48 ± 2.53	76.71 ± 2.49	0.743	75.71 ± 2.59	0.242
FPG (mg/dL)	163.05 ± 7.13	146.10 ± 6.06	< 0.001	135.09 ± 5.71	< 0.001
HbA1c (%)	8.08 ± 0.12	7.25 ± 0.12	< 0.001	7.11 ± 0.15	< 0.001
LDL-cholesterol (mg/dL)	117.91 ± 5.84	116.95 ± 6.67	0.939	116.67 ± 5.18	0.901
HDL-cholesterol (mg/dL)	53.67 ± 2.59	51.95 ± 2.71	0.445	56.24 ± 2.96	0.185
Triglycerides (mg/dL)	153.43 ± 14.05	157.95 ± 17.71	0.855	126.00 ± 13.39	0.048
AST (IU/L)	24.29 ± 1.77	21.71 ± 1.40	0.084	22.09 ± 1.25	0.155
ALT (IU/L)	29.05 ± 3.32	24.48 ± 2.77	0.004	23.95 ± 2.47	0.001
γ-GTP (IU/L)	42.90 ± 7.79	36.19 ± 6.17	0.107	37.10 ± 6.70	0.177

↓ Table 2. Changes in Metabolic Parameters

Baseline

Week 12

P vs. baseline

Week 24

P vs. baseline

Data are expressed as mean ± SE. SE: standard error; BW: body weight; BMI: body mass index; FI: fat index; SMI: skeletal muscle index; SBP: systolic blood pressure; DBP: diastolic blood pressure; FPG: fasting plasma glucose; HbA1c: glycated hemoglobin; LDL: low-density lipoprotein; HDL: high-density lipoprotein; AST: aspartate aminotransferase; ALT: alanine aminotransferase; γ-GTP: γ-glutamyltransferase.

BW (kg)

69.02 ± 2.11

68.69 ± 2.05

0.481

68.74 ± 2.00

0.587

BMI (kg/m²)

25.81 ± 0.70

25.67 ± 0.66

0.408

25.70 ± 0.66

0.563

FI (kg/m²)

7.78 ± 0.76

7.56 ± 0.71

0.145

7.81 ± 0.73

0.960

SMI (kg/m²)

7.90 ± 0.17

8.00 ± 0.19

0.240

7.83 ± 0.19

0.272

SBP (mm Hg)

134.76 ± 2.53

135.19 ± 2.90

0.975

134.00 ± 2.69

0.925

DBP (mm Hg)

77.48 ± 2.53

76.71 ± 2.49

0.743

75.71 ± 2.59

0.242

FPG (mg/dL)

163.05 ± 7.13

146.10 ± 6.06

< 0.001

135.09 ± 5.71

< 0.001

HbA1c (%)

8.08 ± 0.12

7.25 ± 0.12

< 0.001

7.11 ± 0.15

< 0.001

LDL-cholesterol (mg/dL)

117.91 ± 5.84

116.95 ± 6.67

0.939

116.67 ± 5.18

0.901

HDL-cholesterol (mg/dL)

53.67 ± 2.59

51.95 ± 2.71

0.445

56.24 ± 2.96

0.185

Triglycerides (mg/dL)

153.43 ± 14.05

157.95 ± 17.71

0.855

126.00 ± 13.39

0.048

AST (IU/L)

24.29 ± 1.77

21.71 ± 1.40

0.084

22.09 ± 1.25

0.155

ALT (IU/L)

29.05 ± 3.32

24.48 ± 2.77

0.004

23.95 ± 2.47

0.001

γ-GTP (IU/L)

42.90 ± 7.79

36.19 ± 6.17

0.107

37.10 ± 6.70

0.177

↓ **Table 3.** Effect of Imeglimin on RBC Parameters and Serum VB12
	Baseline	Week 12	P vs. baseline	Week 24	P vs. baseline
Data are expressed as mean ± SE. SE: standard error; RBC: red blood cell; Hb: hemoglobin; MCV: mean corpuscular volume; VB: vitamin B.
RBC (10⁶/mm³)
Total	498.86 ± 11.08	476.52 ± 10.35	< 0.001	477.86 ± 10.81	< 0.001
With metformin	524.13 ± 21.45	503.13 ± 20.45	0.028	497.25 ± 20.79	0.006
Without metformin	483.31 ± 10.61	460.15 ± 8.93	0.010	465.92 ± 11.32	0.056
Hb (g/dL)
Total	14.60 ± 0.30	13.98 ± 0.28	< 0.001	14.25 ± 0.32	0.042
With metformin	15.15 ± 0.58	14.54 ± 0.57	0.006	14.60 ± 0.62	0.013
Without metformin	14.27 ± 0.31	13.64 ± 0.25	0.014	14.04 ± 0.36	0.465
MCV (fL)
Total	89.57 ± 0.84	90.79 ± 0.77	< 0.001	92.49 ± 0.70	< 0.001
With metformin	88.68 ± 1.59	89.41 ± 1.46	0.248	91.01 ± 1.19	< 0.001
Without metformin	90.12 ± 0.97	91.63 ± 0.81	< 0.001	93.39 ± 0.79	< 0.001
VB12 (pg/mL)
Total	291.94 ± 26.39	251.61 ± 22.38	0.039	264.00 ± 23.59	0.180
With metformin	323.25 ± 51.75	262.75 ± 40.96	0.017	249.75 ± 41.28	0.004
Without metformin	266.90 ± 23.32	242.71 ± 25.27	0.484	275.40 ± 28.27	0.906

↓ Table 3. Effect of Imeglimin on RBC Parameters and Serum VB12

Baseline

Week 12

P vs. baseline

Week 24

P vs. baseline

Data are expressed as mean ± SE. SE: standard error; RBC: red blood cell; Hb: hemoglobin; MCV: mean corpuscular volume; VB: vitamin B.

RBC (10⁶/mm³)

Total

498.86 ± 11.08

476.52 ± 10.35

< 0.001

477.86 ± 10.81

< 0.001

With metformin

524.13 ± 21.45

503.13 ± 20.45

0.028

497.25 ± 20.79

0.006

Without metformin

483.31 ± 10.61

460.15 ± 8.93

0.010

465.92 ± 11.32

0.056

Hb (g/dL)

Total

14.60 ± 0.30

13.98 ± 0.28

< 0.001

14.25 ± 0.32

0.042

With metformin

15.15 ± 0.58

14.54 ± 0.57

0.006

14.60 ± 0.62

0.013

Without metformin

14.27 ± 0.31

13.64 ± 0.25

0.014

14.04 ± 0.36

0.465

MCV (fL)

Total

89.57 ± 0.84

90.79 ± 0.77

< 0.001

92.49 ± 0.70

< 0.001

With metformin

88.68 ± 1.59

89.41 ± 1.46

0.248

91.01 ± 1.19

< 0.001

Without metformin

90.12 ± 0.97

91.63 ± 0.81

< 0.001

93.39 ± 0.79

< 0.001

VB12 (pg/mL)

Total

291.94 ± 26.39

251.61 ± 22.38

0.039

264.00 ± 23.59

0.180

With metformin

323.25 ± 51.75

262.75 ± 40.96

0.017

249.75 ± 41.28

0.004

Without metformin

266.90 ± 23.32

242.71 ± 25.27

0.484

275.40 ± 28.27

0.906

↓ **Table 4.** Baseline Characteristics of Subgroups With and Without Metformin
	Group with metformin	Group without metformin	P
Data are expressed as mean ± SE. SE: standard error; BMI: body mass index; HbA1c: glycated hemoglobin; eGFR: estimated glomerular filtration rate; UACR: urinary albumin-to-creatinine ratio.
N (men/women)	8 (6/2)	13 (8/5)
Age (years)	63.32 ± 4.175	66.41 ± 2.919	0.281
BMI (kg/m²)	26.83 ± 1.081	25.19 ± 0.835	0.132
HbA1c (%)	8.19 ± 0.263	8.11 ± 0.143	0.263
eGFR (mL/min/1.73m²)	70.5 ± 4.09	67.2 ± 3.23	0.275
UACR (mg/gCre)	84.5 ± 16.7	110.1 ± 16.6	0.195

↓ Table 4. Baseline Characteristics of Subgroups With and Without Metformin

Group with metformin

Group without metformin

Data are expressed as mean ± SE. SE: standard error; BMI: body mass index; HbA1c: glycated hemoglobin; eGFR: estimated glomerular filtration rate; UACR: urinary albumin-to-creatinine ratio.

N (men/women)

8 (6/2)

13 (8/5)

Age (years)

63.32 ± 4.175

66.41 ± 2.919

0.281

BMI (kg/m²)

26.83 ± 1.081

25.19 ± 0.835

0.132

HbA1c (%)

8.19 ± 0.263

8.11 ± 0.143

0.263

eGFR (mL/min/1.73m²)

70.5 ± 4.09

67.2 ± 3.23

0.275

UACR (mg/gCre)

84.5 ± 16.7

110.1 ± 16.6

0.195