Table 4 Stratified analysis 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

Incident peripheral neuropathy

Two-year follow-up

Five-year follow-up

aORa

95% CI

p-value

aORa

95% CI

p-value

In female patients

 cDDD of metformin use

  DDD < 300

1.99

1.85

–

2.15

 < 0.001

1.74

1.67

–

1.81

 < 0.001

  DDD 300–500

2.21

1.77

–

2.77

 < 0.001

1.87

1.64

–

2.13

 < 0.001

  DDD > 500

1.00

0.25

–

4.03

0.996

1.28

0.68

–

2.40

0.439

 Intensity of metformin use

   < 10

1.96

1.82

–

2.12

 < 0.001

1.72

1.65

–

1.79

 < 0.001

  10–25

2.08

1.92

–

2.26

 < 0.001

1.79

1.71

–

1.88

 < 0.001

   > 25

2.16

1.73

–

2.71

 < 0.001

1.84

1.62

–

2.10

 < 0.001

In male patients

 cDDD of metformin use

  DDD < 300

1.57

1.48

–

1.67

 < 0.001

1.51

1.46

–

1.56

 < 0.001

  DDD 300–500

1.86

1.55

–

2.23

 < 0.001

1.64

1.48

–

1.83

 < 0.001

  DDD > 500

2.84

1.50

–

5.38

 < 0.001

2.36

1.58

–

3.52

 < 0.001

 Intensity of metformin use

   < 10

1.01

0.53

–

1.92

0.976

1.04

0.70

–

1.56

0.834

  10–25

1.07

0.56

–

2.03

0.842

1.06

0.71

–

1.59

0.762

   > 25

0.79

0.21

–

2.99

0.733

0.80

0.35

–

1.83

0.591

In patients aged 20–49

 cDDD of metformin use

  DDD < 300

1.85

1.68

–

2.03

 < 0.001

1.71

1.62

–

1.80

 < 0.001

  DDD 300–500

2.45

1.92

–

3.14

 < 0.001

1.89

1.64

–

2.19

 < 0.001

  DDD > 500

3.29

1.34

–

8.11

0.010

2.05

1.12

–

3.75

0.020

 Intensity of metformin use

   < 10

1.83

1.66

–

2.01

 < 0.001

1.71

1.62

–

1.80

 < 0.001

  10–25

1.88

1.69

–

2.09

 < 0.001

1.72

1.62

–

1.82

 < 0.001

   > 25

2.47

1.94

–

3.15

 < 0.001

1.90

1.64

–

2.20

 < 0.001

In patients aged 50–54

 cDDD of metformin use

  DDD < 300

1.99

1.79

–

2.22

 < 0.001

1.67

1.57

–

1.77

 < 0.001

  DDD 300–500

1.76

1.20

–

2.58

0.004

1.74

1.42

–

2.13

 < 0.001

  DDD > 500

2.97

0.72

–

12.15

0.131

3.05

1.50

–

6.19

0.002

 Intensity of metformin use

   < 10

1.17

0.28

–

4.88

0.832

0.95

0.46

–

1.94

0.882

  10–25

1.21

0.29

–

5.05

0.797

0.95

0.46

–

1.95

0.890

   > 25

0.62

0.03

–

11.84

0.747

0.56

0.13

–

2.48

0.447

In patients aged 55–59

 cDDD of metformin use

1.76

1.58

–

1.96

 < 0.001

1.66

1.56

–

1.76

 < 0.001

  DDD < 300

2.58

1.84

–

3.61

 < 0.001

2.11

1.72

–

2.59

 < 0.001

  DDD 300–500

1.00

0.14

–

7.33

1.000

1.77

0.72

–

4.34

0.213

  DDD > 500

          

 Intensity of metformin use

   < 10

4.41

0.61

–

32.05

0.143

1.96

0.80

–

4.81

0.142

  10–25

4.94

0.68

–

35.95

0.115

2.03

0.83

–

4.98

0.123

   > 25

17.19

0.31

–

951.55

0.165

3.01

0.48

–

18.89

0.240

In patients aged ≥ 65

 cDDD of metformin use

  DDD < 300

1.62

1.50

–

1.76

 < 0.001

1.47

1.40

–

1.53

 < 0.001

  DDD 300–500

1.82

1.29

–

2.58

 < 0.001

1.72

1.41

–

2.09

 < 0.001

  DDD > 500

1.40

0.34

–

5.74

0.637

1.73

0.88

–

3.37

0.110

 Intensity of metformin use

   < 10

2.05

0.49

–

8.54

0.322

1.43

0.72

–

2.82

0.304

  10–25

2.27

0.55

–

9.46

0.259

1.56

0.79

–

3.09

0.197

   > 25

3.07

0.16

–

57.84

0.454

1.70

0.42

–

7.01

0.460

In patients with DCSI score 0

 cDDD of metformin use

  DDD < 300

1.83

1.71

–

1.96

 < 0.001

1.67

1.60

–

1.73

 < 0.001

  DDD 300–500

2.39

1.98

–

2.88

 < 0.001

1.92

1.71

–

2.14

 < 0.001

  DDD > 500

3.96

1.95

–

8.05

 < 0.001

2.97

1.92

–

4.59

 < 0.001

 Intensity of metformin use

   < 10

1.81

1.69

–

1.94

 < 0.001

1.66

1.60

–

1.72

 < 0.001

  10–25

1.86

1.73

–

2.00

 < 0.001

1.67

1.60

–

1.74

 < 0.001

   > 25

2.42

2.01

–

2.92

 < 0.001

1.94

1.74

–

2.17

 < 0.001

In patients with DCSI score 1

 cDDD of metformin use

  DDD < 300

2.01

1.76

–

2.28

 < 0.001

1.98

1.84

–

2.13

 < 0.001

  DDD 300–500

2.65

1.87

–

3.74

 < 0.001

2.59

2.11

–

3.16

 < 0.001

  DDD > 500

3.13

0.97

–

10.08

0.056

2.19

0.97

–

4.95

0.060

 Intensity of metformin use

   < 10

1.68

0.52

–

5.38

0.386

2.31

1.02

–

5.23

0.045

  10–25

1.74

0.54

–

5.60

0.353

2.42

1.07

–

5.49

0.034

   > 25

1.89

0.17

–

21.00

0.606

3.61

0.68

–

19.26

0.133

In patients with DCSI score ≥ 2

 cDDD of metformin use

  DDD < 300

2.22

1.90

–

2.60

 < 0.001

1.88

1.72

–

2.05

 < 0.001

  DDD 300–500

2.58

1.73

–

3.87

 < 0.001

2.30

1.83

–

2.90

 < 0.001

  DDD > 500

1.16

0.16

–

8.57

0.885

2.25

1.08

–

4.66

0.030

 Intensity of metformin use

   < 10

4.72

0.65

–

34.44

0.126

1.89

0.92

–

3.86

0.083

  10–25

5.76

0.79

–

42.07

0.084

2.08

1.01

–

4.27

0.046

   > 25

13.09

0.23

–

740.24

0.212

2.45

0.55

–

10.84

0.238

  1. aaOR, adjusted odds ratio. Extraneous factors adjusted in the model were patients’ characteristics, DCSI, and comorbidities.
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