Table 3 Five-year follow-up of incident peripheral neuropathy in new-onset diabetes mellitus patients with metformin.

From: Dose dependent relationship of metformin use and diabetic peripheral neuropathy risk in patients with type 2 diabetes mellitus

Variables

Five-year follow-up of incident peripheral neuropathy

Events

p-value

Model 1

Model 2

N

%

OR

95% CI

p-value

OR

95% CI

p-value

Total

68,024

7.62

           

cDDD of metformin use

 < 0.001

          

 Non-users

24,020

5.79

 

1

    

–

 

–

 

–

  < 300

43,256

9.20

 

1.66

1.61

–

1.71

 < 0.001

–

 

–

 

–

 300–500

713

10.12

 

1.86

1.70

–

2.04

 < 0.001

–

 

–

 

–

  > 500

35

12.41

 

2.07

1.47

–

2.92

 < 0.001

–

 

–

 

–

Intensity of metformin use

 < 0.001

          

 Non-users

24,020

5.79

 

–

 

–

 

–

1

    

  < 10

31,219

9.14

 

–

 

–

 

–

1.64

1.59

–

1.70

 < 0.001

 10–25

12,037

9.34

 

–

 

–

 

–

1.69

1.63

–

1.75

 < 0.001

  > 25

748

10.21

 

–

 

–

 

–

1.87

1.71

–

2.05

 < 0.001

Gender

0.018

          

 Female

32,429

7.69

 

1

    

1

    

 Male

35,595

7.56

 

1.03

1.01

–

1.06

0.013

1.03

1.01

–

1.06

0.014

Age (year)

 < 0.001

          

 20–49

18,448

7.01

 

1

    

1

    

 50–54

11,415

7.79

 

1.18

1.15

–

1.21

 < 0.001

1.18

1.15

–

1.21

 < 0.001

 55–59

10,583

7.46

 

1.16

1.13

–

1.19

 < 0.001

1.16

1.13

–

1.19

 < 0.001

 66–64

8,693

7.70

 

1.20

1.16

–

1.24

 < 0.001

1.20

1.16

–

1.24

 < 0.001

  ≥ 65

18,885

8.26

 

1.27

1.22

–

1.31

 < 0.001

1.27

1.22

–

1.31

 < 0.001

Income level (NTD)a

 < 0.001

          

  ≤ 21,000

40,274

8.91

 

1

    

1

    

 21,001–33,000

13,180

6.23

 

0.69

0.68

–

0.71

 < 0.001

0.69

0.68

–

0.71

 < 0.001

  ≥ 33,001

14,570

6.35

 

0.73

0.72

–

0.74

 < 0.001

0.73

0.72

–

0.74

 < 0.001

Urbanizationb

 < 0.001

          

 Level 1

18,119

7.29

 

1

    

1

    

 Level 2

21,590

7.39

 

0.97

0.95

–

0.99

0.006

0.97

0.95

–

0.99

0.006

 Level 3

11,203

7.84

 

1.01

0.99

–

1.04

0.256

1.01

0.99

–

1.04

0.253

 Level 4

9,911

8.22

 

1.03

1.01

–

1.06

0.018

1.03

1.01

–

1.06

0.016

 Level 5

1,673

8.75

 

1.05

0.99

–

1.10

0.083

1.05

1.00

–

1.10

0.078

 Level 6

2,842

7.81

 

0.92

0.88

–

0.96

 < 0.001

0.92

0.88

–

0.96

 < 0.001

 Level 7

2,686

8.06

 

0.96

0.93

–

1.00

0.075

0.96

0.93

–

1.00

0.076

DCSI scorec

 < 0.001

          

 0

43,926

7.30

 

1

    

1

    

 1

13,248

8.15

 

1.07

1.04

–

1.10

 < 0.001

1.07

1.04

–

1.10

 < 0.001

  ≥ 2

10,850

8.43

 

1.03

0.99

–

1.07

0.130

1.03

0.99

–

1.07

0.138

Hyperuricemia

 < 0.001

          

 No

67,546

7.63

 

1

    

1

    

 Yes

478

6.41

 

0.73

0.72

–

0.75

 < 0.001

0.73

0.72

–

0.75

 < 0.001

CVDc

 < 0.001

          

 No

65,011

7.58

 

1

    

1

    

 Yes

3,013

8.51

 

1.05

1.01

–

1.09

0.024

1.05

1.01

–

1.09

0.026

Alcoholism

0.336

          

 No

67,974

7.62

 

1

    

1

    

 Yes

50

6.62

 

0.88

0.67

–

1.16

0.366

0.88

0.67

–

1.16

0.367

RAc

0.249

          

 No

67,508

7.62

 

1

    

1

    

 Yes

516

8.00

 

1.06

0.97

–

1.16

0.198

1.06

0.97

–

1.16

0.194

Sleep disturbance

0.013

          

 No

54,634

7.58

 

1

    

1

    

 Yes

13,390

7.76

 

1.01

0.99

–

1.03

0.207

1.01

0.99

–

1.03

0.184

SLEc

0.226

          

 No

67,989

7.62

 

1

    

1

    

 Yes

35

6.26

 

0.88

0.63

–

1.22

0.436

0.88

0.63

–

1.22

0.433

Migraine

0.117

          

 No

67,662

7.62

 

1

    

1

    

 Yes

362

8.25

 

1.10

0.99

–

1.22

0.078

1.10

0.99

–

1.22

0.077

CADc

0.661

          

 No

63,358

7.62

 

1

    

1

    

 Yes

4,666

7.57

 

0.94

0.91

–

0.97

 < 0.001

0.94

0.91

–

0.97

 < 0.001

PADc

0.297

          

 No

67,627

7.62

 

1

    

1

    

 Yes

397

8.01

 

0.98

0.89

–

1.08

0.686

0.98

0.89

–

1.08

0.690

Depression

0.648

          

 No

67,382

7.62

 

1

    

1

    

 Yes

642

7.49

 

1.00

0.92

–

1.08

0.955

1.00

0.92

–

1.08

0.956

Sarcopenia

0.538

          

 No

67,986

7.62

 

1

    

1

    

 Yes

38

6.92

 

0.88

0.64

–

1.21

0.434

0.88

0.64

–

1.21

0.435

Obesity

 < 0.001

          

 No

67,691

7.63

 

1

    

1

    

 Yes

333

5.89

 

0.83

0.75

–

0.93

 < 0.001

0.83

0.75

–

0.93

 < 0.001

Diabetic retinopathy

0.307

          

 No

67,087

7.62

 

1

    

1

    

 Yes

937

7.87

 

1.01

0.95

–

1.08

0.808

1.01

0.95

–

1.08

0.812

CKDc

 < 0.001

          

 No

67,710

7.63

 

1

    

1

    

 Yes

314

5.40

 

0.76

0.68

–

0.85

 < 0.001

0.76

0.68

–

0.85

 < 0.001

cDDD of metformin use*Gender

–

–

 

0.94

0.91

–

0.97

 < 0.001

–

 

–

 

–

cDDD of metformin use*Age

–

–

 

0.98

0.97

–

0.99

 < 0.001

–

 

–

 

–

cDDD of metformin use*DCSI

–

–

 

1.12

1.10

–

1.15

 < 0.001

–

 

–

 

–

Intensity of metformin use*Gender

–

–

 

–

 

–

 

–

0.94

0.91

–

0.97

 < 0.001

Intensity of metformin use*Age

–

–

 

–

 

–

 

–

0.98

0.97

–

0.99

 < 0.001

Intensity of metformin use*DCSI

–

–

 

–

 

–

 

–

1.12

1.10

–

1.15

 < 0.001

  1. aThe premium-based salary of the patient which is according to the payroll bracket table of the National Health Insurance Administration Taiwan. NTD is New Taiwan Dollar. NTD 1 ≈ USD 0.034).
  2. bLevel 1 denoted the highest degree of urbanization, whereas level 7 denoted the lowest degree of urbanization.
  3. cDCSI, diabetes complications severity index; CVD, cerebrovascular disease; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; CAD, coronary artery disease; PAD, peripheral arterial disease; CKD, chronic kidney disease.
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