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://www.jofem.org

Original Article

Volume 10, Number 6, December 2020, pages 167-172

Combination Therapy of Alpha-Glucosidase Inhibitor, Thiazolidinedione and Sodium Glucose Co-Transporter-2 Inhibitor in Japanese Type 2 Diabetes Patients

**Table 1.** Dose Levels of Drugs
Name of drug	Dose level (mg/day)
α-GI, α-glucosidase inhibitor; TZD, thiazolidinedione; SGLT2, sodium glucose co-transporter-2.
α-GI
Voglibose	0.9
Miglitol	150
TZD
Pioglitazone	30
SGLT2 inhibitor
Luseogliflozin	2.5
Dapagliflozin	5
Tofogliflozin	20
Empagliflozin	10
Canagliflozin	100

Table 1. Dose Levels of Drugs

Name of drug

Dose level (mg/day)

α-GI, α-glucosidase inhibitor; TZD, thiazolidinedione; SGLT2, sodium glucose co-transporter-2.

α-GI

Voglibose

0.9

Miglitol

150

TZD

Pioglitazone

SGLT2 inhibitor

Luseogliflozin

2.5

Dapagliflozin

Tofogliflozin

Empagliflozin

Canagliflozin

100

**Table 2.** Efficacy of Combined Therapy With α-GI, TZD and SGLT2 Inhibitor in Type 2 Diabetic, Japanese Patients
	Additional SGLT2 inhibitor treatment group (n = 14, eight males, six females)	α-GI + SGLT2 inhibitor treatment group (n = 17, 11 males, six females)	TZD + SGLT2 inhibitor group (n = 5, five males, 0 females)	α-GI + TZD + SGLT2 inhibitor group (n = 24, 18 males, six females)
Data are expressed as mean ± standard deviation. P < 0.05, *P < 0.01 vs. ”Before“ data. α-GI, α-glucosidase inhibitor; TZD, thiazolidinedione; SGLT2, sodium glucose co-transporter-2; BMI, body mass index; HbA1c, hemoglobin A1c; AST, aspartate aminotransferase; ALT, alanine aminotransferase; γ-GTP, γ-glutamyl transpeptidase; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.
Age (years)	55 ± 12	53 ± 11	55 ± 6	54 ± 10
Duration of diabetes mellitus (years)	12 ± 8	14 ± 8	5 ± 2	14 ± 6
Body weight (kg)	70.7 ± 13.5	69.2 ± 12.8	68.8 ± 13.0*	67.8 ± 12.2**	77.8 ± 13.6	73.4 ± 12.5**	72.8 ± 12.5**	72.6 ± 12.5**	87.7 ± 25.7	85.1 ± 25.6	81.0 ± 20.9	82.5 ± 20.9	79.0 ± 14.0	76.1 ± 13.9**	75.6 ± 14.1**	75.1 ± 14.2**
BMI (kg/m²)	26.3 ± 3.4	25.7 ± 3.2	25.6 ± 3.1*	25.2 ± 3.1**	27.9 ± 3.7	26.3 ± 3.7**	26.1 ± 3.7**	26.1 ± 3.8**	29.2 ± 7.4	28.3 ± 7.4	27.0 ± 6.3	27.5 ± 6.3	28.4 ± 5.3	27.5 ± 5.1**	27.4 ± 5.2**	27.2 ± 5.2**
HbA1c (%)	7.4 ± 0.7	7.2 ± 0.7	7.1 ± 0.7	7.5 ± 1.1	7.3 ± 0.9	7.1 ± 1.0	7.2 ± 1.2	7.2 ± 1.0	6.7 ± 0.1	6.4 ± 0.2	6.5 ± 0.4	6.7 ± 0.4	7.1 ± 0.6	6.7 ± 0.7**	6.7 ± 0.6**	6.8 ± 0.8*
AST (U/L)	29 ± 21	20 ± 6	20 ± 6	22 ± 8	28 ± 18	20 ± 7	21 ± 9	22 ± 8	24 ± 13	21 ± 8	35 ± 29	23 ± 13	26 ± 15	20 ± 6**	21 ± 7*	24 ± 11
ALT (U/L)	24 ± 13	25 ± 18	22 ± 15	24 ± 18	31 ± 13	26 ± 11	27 ± 14*	31 ± 25	29 ± 17	24 ± 12	35 ± 24	26 ± 20	28 ± 21	20 ± 12**	21 ± 13*	22 ± 15*
γ-GTP (U/L)	42 ± 30	35 ± 22	34 ± 23	36 ± 29	29 ± 23	25 ± 17	27 ± 25	26 ± 27	66 ± 51	36 ± 17	38 ± 17	57 ± 43	28 ± 21	28 ± 23	28 ± 22	33 ± 38
Uric acid (mg/dL)	5.3 ± 1.9	4.5 ± 1.3**	4.5 ± 1.4**	4.7 ± 1.5*	5.0 ± 0.9	4.5 ± 1.1**	4.5 ± 1.2**	4.8 ± 1.2	5.9 ± 1.5	4.9 ± 1.4*	4.9 ± 1.0*	5.3 ± 1.3	5.1 ± 1.1	4.6 ± 1.2**	4.7 ± 1.0	4.5 ± 1.1**
Total cholesterol (mg/dL)	171 ± 20	173 ± 17	173 ± 19	175 ± 36	166 ± 16	169 ± 22	165 ± 19	169 ± 22	186 ± 47	197 ± 37	199 ± 37	194 ± 52	171 ± 31	177 ± 30	188 ± 36**	178 ± 31
HDL-C (mg/dL)	58 ± 13	60 ± 15	62 ± 14	60 ± 16	53 ± 11	54 ± 14	55 ± 12	56 ± 14	61 ± 15	66 ± 18	72 ± 21	67 ± 19	62 ± 15	65 ± 20	67 ± 17*	67 ± 17*
LDL-C (mg/dL)	94 ± 19	98 ± 15	94 ± 16	93 ± 25	93 ± 18	92 ± 20	91 ± 17	93 ± 21	109 ± 31	114 ± 25	114 ± 18	112 ± 34	89 ± 25	89 ± 25	102 ± 31*	92 ± 26
LDL-C/HDL-C ratio	1.72 ± 0.58	1.75 ± 0.62	1.62 ± 0.51	1.64 ± 0.61	1.82 ± 0.55	1.83 ± 0.57	1.75 ± 0.54	1.79 ± 0.66	1.76 ± 0.26	1.76 ± 0.32	1.66 ± 0.41	1.68 ± 0.15	1.50 ± 0.42	1.47 ± 0.51	1.64 ± 0.78	1.46 ± 0.52
Triglyceride (mg/dL)	132 ± 47	128 ± 73	141 ± 72	111 ± 57	131 ± 54	146 ± 70	134 ± 62	126 ± 60	157 ± 85	121 ± 41	112 ± 36	112 ± 47	111 ± 51	134 ± 60	114 ± 74	108 ± 62

Table 2. Efficacy of Combined Therapy With α-GI, TZD and SGLT2 Inhibitor in Type 2 Diabetic, Japanese Patients

Additional SGLT2 inhibitor treatment group (n = 14, eight males, six females)

α-GI + SGLT2 inhibitor treatment group (n = 17, 11 males, six females)

TZD + SGLT2 inhibitor group (n = 5, five males, 0 females)

α-GI + TZD + SGLT2 inhibitor group (n = 24, 18 males, six females)

Before

1 year

2 years

3 years

Before

1 year

2 years

3 years

Before

1 year

2 years

3 years

Before

1 year

2 years

3 years

Data are expressed as mean ± standard deviation. *P < 0.05, **P < 0.01 vs. ”Before“ data. α-GI, α-glucosidase inhibitor; TZD, thiazolidinedione; SGLT2, sodium glucose co-transporter-2; BMI, body mass index; HbA1c, hemoglobin A1c; AST, aspartate aminotransferase; ALT, alanine aminotransferase; γ-GTP, γ-glutamyl transpeptidase; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.

Age (years)

55 ± 12

53 ± 11

55 ± 6

54 ± 10

Duration of diabetes mellitus (years)

12 ± 8

14 ± 8

5 ± 2

14 ± 6

Body weight (kg)

70.7 ± 13.5

69.2 ± 12.8

68.8 ± 13.0*

67.8 ± 12.2**

77.8 ± 13.6

73.4 ± 12.5**

72.8 ± 12.5**

72.6 ± 12.5**

87.7 ± 25.7

85.1 ± 25.6

81.0 ± 20.9

82.5 ± 20.9

79.0 ± 14.0

76.1 ± 13.9**

75.6 ± 14.1**

75.1 ± 14.2**

BMI (kg/m²)

26.3 ± 3.4

25.7 ± 3.2

25.6 ± 3.1*

25.2 ± 3.1**

27.9 ± 3.7

26.3 ± 3.7**

26.1 ± 3.7**

26.1 ± 3.8**

29.2 ± 7.4

28.3 ± 7.4

27.0 ± 6.3

27.5 ± 6.3

28.4 ± 5.3

27.5 ± 5.1**

27.4 ± 5.2**

27.2 ± 5.2**

HbA1c (%)

7.4 ± 0.7

7.2 ± 0.7

7.1 ± 0.7

7.5 ± 1.1

7.3 ± 0.9

7.1 ± 1.0

7.2 ± 1.2

7.2 ± 1.0

6.7 ± 0.1

6.4 ± 0.2

6.5 ± 0.4

6.7 ± 0.4

7.1 ± 0.6

6.7 ± 0.7**

6.7 ± 0.6**

6.8 ± 0.8*

AST (U/L)

29 ± 21

20 ± 6

22 ± 8

28 ± 18

20 ± 7

21 ± 9

22 ± 8

24 ± 13

21 ± 8

35 ± 29

23 ± 13

26 ± 15

20 ± 6**

21 ± 7*

24 ± 11

ALT (U/L)

24 ± 13

25 ± 18

22 ± 15

24 ± 18

31 ± 13

26 ± 11

27 ± 14*

31 ± 25

29 ± 17

24 ± 12

35 ± 24

26 ± 20

28 ± 21

20 ± 12**

21 ± 13*

22 ± 15*

γ-GTP (U/L)

42 ± 30

35 ± 22

34 ± 23

36 ± 29

29 ± 23

25 ± 17

27 ± 25

26 ± 27

66 ± 51

36 ± 17

38 ± 17

57 ± 43

28 ± 21

28 ± 23

28 ± 22

33 ± 38

Uric acid (mg/dL)

5.3 ± 1.9

4.5 ± 1.3**

4.5 ± 1.4**

4.7 ± 1.5*

5.0 ± 0.9

4.5 ± 1.1**

4.5 ± 1.2**

4.8 ± 1.2

5.9 ± 1.5

4.9 ± 1.4*

4.9 ± 1.0*

5.3 ± 1.3

5.1 ± 1.1

4.6 ± 1.2**

4.7 ± 1.0

4.5 ± 1.1**

Total cholesterol (mg/dL)

171 ± 20

173 ± 17

173 ± 19

175 ± 36

166 ± 16

169 ± 22

165 ± 19

169 ± 22

186 ± 47

197 ± 37

199 ± 37

194 ± 52

171 ± 31

177 ± 30

188 ± 36**

178 ± 31

HDL-C (mg/dL)

58 ± 13

60 ± 15

62 ± 14

60 ± 16

53 ± 11

54 ± 14

55 ± 12

56 ± 14

61 ± 15

66 ± 18

72 ± 21

67 ± 19

62 ± 15

65 ± 20

67 ± 17*

LDL-C (mg/dL)

94 ± 19

98 ± 15

94 ± 16

93 ± 25

93 ± 18

92 ± 20

91 ± 17

93 ± 21

109 ± 31

114 ± 25

114 ± 18

112 ± 34

89 ± 25

102 ± 31*

92 ± 26

LDL-C/HDL-C ratio

1.72 ± 0.58

1.75 ± 0.62

1.62 ± 0.51

1.64 ± 0.61

1.82 ± 0.55

1.83 ± 0.57

1.75 ± 0.54

1.79 ± 0.66

1.76 ± 0.26

1.76 ± 0.32

1.66 ± 0.41

1.68 ± 0.15

1.50 ± 0.42

1.47 ± 0.51

1.64 ± 0.78

1.46 ± 0.52

Triglyceride (mg/dL)

132 ± 47

128 ± 73

141 ± 72

111 ± 57

131 ± 54

146 ± 70

134 ± 62

126 ± 60

157 ± 85

121 ± 41

112 ± 36

112 ± 47

111 ± 51

134 ± 60

114 ± 74

108 ± 62