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 http://www.jocmr.org

Original Article

Volume 8, Number 8, August 2016, pages 585-590

The Influences of Withdrawal and Daily Dose Reduction of Pioglitazone on Metabolic Parameters in Patients With Type 2 Diabetes: A Retrospective Longitudinal Observational Study

**Table 1.** Baseline Characteristics of the Study Subjects Who Had Undergone the Withdrawal of Pioglitazone (n = 20)
Age	68 ± 12
Sex (male/female)	13/7
Body height (cm)	157 ± 10
Body weight (kg)	73.1 ± 12.2
Body mass index (kg/m²)	28.5 ± 3.5
Plasma glucose (mg/dL)	172 ± 63
Hemoglobin A1c (%)	6.9 ± 0.9
Daily dose of pioglitazone (mg)	23 ± 10

Table 1. Baseline Characteristics of the Study Subjects Who Had Undergone the Withdrawal of Pioglitazone (n = 20)

Age

68 ± 12

Sex (male/female)

13/7

Body height (cm)

157 ± 10

Body weight (kg)

73.1 ± 12.2

Body mass index (kg/m²)

28.5 ± 3.5

Plasma glucose (mg/dL)

172 ± 63

Hemoglobin A1c (%)

6.9 ± 0.9

Daily dose of pioglitazone (mg)

23 ± 10

**Table 2.** Baseline Characteristics of the Study Subjects Who Had Undergone the Daily Dose Reduction of Pioglitazone (n = 51)
Age	63 ± 12
Sex (male/female)	29/22
Body height (cm)	163 ± 9
Body weight (kg)	72.5 ± 20.5
Body mass index (kg/m²)	27.7 ± 5.8
Plasma glucose (mg/dL)	163 ± 66
Hemoglobin A1c (%)	7.2 ± 1.3
Daily dose of pioglitazone (mg)	30 ± 10

Table 2. Baseline Characteristics of the Study Subjects Who Had Undergone the Daily Dose Reduction of Pioglitazone (n = 51)

Age

63 ± 12

Sex (male/female)

29/22

Body height (cm)

163 ± 9

Body weight (kg)

72.5 ± 20.5

Body mass index (kg/m²)

27.7 ± 5.8

Plasma glucose (mg/dL)

163 ± 66

Hemoglobin A1c (%)

7.2 ± 1.3

Daily dose of pioglitazone (mg)

30 ± 10

**Table 3.** Other Hypoglycemic or Lipid Modifying Agents Which Subjects Had Taken Before and After the Withdrawal of Pioglitazone (n = 20)
Hypoglycemic and lipid modifying agents	Before withdrawal	3 months after withdrawal	6 months after withdrawal
Metformin	8 (40%)	9 (45%)	9 (45%)
Metformin at high dose (≥ 1,000 mg)	0 (0%)	4 (20%)	4 (20%)
Sulfonylureas	3 (15%)	3 (15%)	5 (25%)
Dipeptidyl peptidase-4 inhibitors	1 (5%)	11 (55%)	12 (60%)
α-glucosidase inhibitors	7 (35%)	6 (30%)	6 (30%)
Glinides	0 (0%)	0 (0%)	0 (0%)
Insulin	2 (10%)	2 (10%)	2 (10%)
Statins	6 (30%)	6 (30%)	6 (30%)
Fibrates	1 (5%)	0 (0%)	0 (0%)

Table 3. Other Hypoglycemic or Lipid Modifying Agents Which Subjects Had Taken Before and After the Withdrawal of Pioglitazone (n = 20)

Hypoglycemic and lipid modifying agents

Before withdrawal

3 months after withdrawal

6 months after withdrawal

Metformin

8 (40%)

9 (45%)

Metformin at high dose (≥ 1,000 mg)

0 (0%)

4 (20%)

Sulfonylureas

3 (15%)

5 (25%)

Dipeptidyl peptidase-4 inhibitors

1 (5%)

11 (55%)

12 (60%)

α-glucosidase inhibitors

7 (35%)

6 (30%)

Glinides

0 (0%)

Insulin

2 (10%)

Statins

6 (30%)

Fibrates

1 (5%)

0 (0%)

**Table 4.** Other Hypoglycemic or Lipid Modifying Agents Which Subjects Had Taken Before and After the Daily Dose Reduction of Pioglitazone (n = 51)
Hypoglycemic and lipid modifying agents	Before reduction	3 months after reduction	6 months after reduction
Metformin	29 (57%)	32 (63%)	33 (65%)
Metformin at high dose (≥ 1,000 mg)	15 (29%)	21 (41%)	25 (49%)
Sulfonylureas	15 (29%)	14 (27%)	14 (27%)
Dipeptidyl peptidase-4 inhibitors	19 (37%)	24 (47%)	24 (47%)
α-glucosidase inhibitors	26 (51%)	24 (47%)	25 (49%)
Glinides	3 (6%)	6 (12%)	6 (12%)
Insulin	3 (6%)	3 (6%)	4 (8%)
Statins	26 (51%)	28 (55%)	29 (57%)
Fibrates	1 (2%)	1 (2%)	1 (2%)

Table 4. Other Hypoglycemic or Lipid Modifying Agents Which Subjects Had Taken Before and After the Daily Dose Reduction of Pioglitazone (n = 51)

Hypoglycemic and lipid modifying agents

Before reduction

3 months after reduction

6 months after reduction

Metformin

29 (57%)

32 (63%)

33 (65%)

Metformin at high dose (≥ 1,000 mg)

15 (29%)

21 (41%)

25 (49%)

Sulfonylureas

15 (29%)

14 (27%)

Dipeptidyl peptidase-4 inhibitors

19 (37%)

24 (47%)

α-glucosidase inhibitors

26 (51%)

24 (47%)

25 (49%)

Glinides

3 (6%)

6 (12%)

Insulin

3 (6%)

4 (8%)

Statins

26 (51%)

28 (55%)

29 (57%)

Fibrates

1 (2%)

**Table 5.** Changes of Clinical Parameters 3 Months After the Withdrawal of Pioglitazone
	n	Before withdrawal	3 months after withdrawal	P values
Body weight (kg)	6	72.2 ± 13.8	70.0 ± 14.0	0.193
Plasma glucose (mg/dL)	17	172 ± 66	142 ± 49	0.184
Hemoglobin A1c (%)	14	6.7 ± 0.9	6.7 ± 0.7	0.790
HDL-cholesterol (mg/dL)	17	53 ± 16	48 ± 16	0.004
LDL-cholesterol (mg/dL)	14	91 ± 26	88 ± 19	0.608
Triglyceride (mg/dL)	18	166 ± 123	137 ± 69	0.336
Aspartate aminotransferase (IU/L)	18	22 ± 8	24 ± 9	0.193
Alanine aminotransferase (IU/L)	18	19 ± 11	24 ± 14	0.008
Creatinine (mg/dL)	18	0.86 ± 0.21	0.84 ± 0.22	0.663

Table 5. Changes of Clinical Parameters 3 Months After the Withdrawal of Pioglitazone

Before withdrawal

3 months after withdrawal

P values

Body weight (kg)

72.2 ± 13.8

70.0 ± 14.0

0.193

Plasma glucose (mg/dL)

172 ± 66

142 ± 49

0.184

Hemoglobin A1c (%)

6.7 ± 0.9

6.7 ± 0.7

0.790

HDL-cholesterol (mg/dL)

53 ± 16

48 ± 16

0.004

LDL-cholesterol (mg/dL)

91 ± 26

88 ± 19

0.608

Triglyceride (mg/dL)

166 ± 123

137 ± 69

0.336

Aspartate aminotransferase (IU/L)

22 ± 8

24 ± 9

0.193

Alanine aminotransferase (IU/L)

19 ± 11

24 ± 14

0.008

Creatinine (mg/dL)

0.86 ± 0.21

0.84 ± 0.22

0.663

**Table 6.** Changes of Clinical Parameters 6 Months After the Withdrawal of Pioglitazone
	n	Before withdrawal	6 months after withdrawal	P values
Body weight (kg)	10	73.5 ± 12.8	71.4 ± 12.4	0.101
Plasma glucose (mg/dL)	17	172 ± 66	158 ± 62	0.421
Hemoglobin A1c (%)	14	6.7 ± 1.0	6.7 ± 0.8	0.849
HDL-cholesterol (mg/dL)	17	53 ± 16	48 ± 15	0.006
LDL-cholesterol (mg/dL)	14	91 ± 26	86 ± 20	0.603
Triglyceride (mg/dL)	17	160 ± 124	133 ± 71	0.304
Aspartate aminotransferase (IU/L)	18	22 ± 8	23 ± 9	0.759
Alanine aminotransferase (IU/L)	18	19 ± 11	21 ± 16	0.318
Creatinine (mg/dL)	18	0.86 ± 0.21	0.84 ± 0.20	0.659

Table 6. Changes of Clinical Parameters 6 Months After the Withdrawal of Pioglitazone

Before withdrawal

6 months after withdrawal

P values

Body weight (kg)

73.5 ± 12.8

71.4 ± 12.4

0.101

Plasma glucose (mg/dL)

172 ± 66

158 ± 62

0.421

Hemoglobin A1c (%)

6.7 ± 1.0

6.7 ± 0.8

0.849

HDL-cholesterol (mg/dL)

53 ± 16

48 ± 15

0.006

LDL-cholesterol (mg/dL)

91 ± 26

86 ± 20

0.603

Triglyceride (mg/dL)

160 ± 124

133 ± 71

0.304

Aspartate aminotransferase (IU/L)

22 ± 8

23 ± 9

0.759

Alanine aminotransferase (IU/L)

19 ± 11

21 ± 16

0.318

Creatinine (mg/dL)

0.86 ± 0.21

0.84 ± 0.20

0.659

**Table 7.** Changes of Clinical Parameters 3 Months After the Daily Dose Reduction of Pioglitazone
	n	Before dose reduction	3 months after dose reduction	P values
Body weight (kg)	34	75.0 ± 2.10	74.1 ± 20.1	0.030
Plasma glucose (mg/dL)	41	162 ± 69	150 ± 57	0.144
Hemoglobin A1c (%)	35	7.2 ± 1.3	7.3 ±1.5	0.245
HDL-cholesterol (mg/dL)	41	54 ± 16	55 ± 16	0.411
LDL-cholesterol (mg/dL)	26	99 ± 21	103 ± 27	0.427
Triglyceride (mg/dL)	41	155 ± 141	137 ± 107	0.217
Aspartate aminotransferase (IU/L)	42	27 ± 18	26 ± 12	0.716
Alanine aminotransferase (IU/L)	42	27 ± 23	26 ± 18	0.713
Creatinine (mg/dL)	41	0.76 ± 0.25	0.75 ± 0.23	0.480

Table 7. Changes of Clinical Parameters 3 Months After the Daily Dose Reduction of Pioglitazone

Before dose reduction

3 months after dose reduction

P values

Body weight (kg)

75.0 ± 2.10

74.1 ± 20.1

0.030

Plasma glucose (mg/dL)

162 ± 69

150 ± 57

0.144

Hemoglobin A1c (%)

7.2 ± 1.3

7.3 ±1.5

0.245

HDL-cholesterol (mg/dL)

54 ± 16

55 ± 16

0.411

LDL-cholesterol (mg/dL)

99 ± 21

103 ± 27

0.427

Triglyceride (mg/dL)

155 ± 141

137 ± 107

0.217

Aspartate aminotransferase (IU/L)

27 ± 18

26 ± 12

0.716

Alanine aminotransferase (IU/L)

27 ± 23

26 ± 18

0.713

Creatinine (mg/dL)

0.76 ± 0.25

0.75 ± 0.23

0.480

**Table 8.** Changes of Clinical Parameters 6 Months After the Daily Dose Reduction of Pioglitazone
	n	Before dose reduction	6 months after dose reduction	P values
Body weight (kg)	27	77.6 ± 21.5	76.3 ± 20.9	0.015
Plasma glucose (mg/dL)	39	161 ± 71	163 ± 60	0.823
Hemoglobin A1c (%)	35	7.3 ± 1.5	7.4 ± 1.3	0.470
HDL-cholesterol (mg/dL)	39	54 ± 16	54 ± 14	0.744
LDL-cholesterol (mg/dL)	24	97 ± 23	101 ± 23	0.366
Triglyceride (mg/dL)	39	148 ± 142	149 ± 128	0.932
Aspartate aminotransferase (IU/L)	39	26 ± 19	24 ± 7	0.272
Alanine aminotransferase (IU/L)	38	27 ± 23	25 ± 12	0.457
Creatinine (mg/dL)	39	0.76 ± 0.25	0.76 ± 0.25	0.966

Table 8. Changes of Clinical Parameters 6 Months After the Daily Dose Reduction of Pioglitazone

Before dose reduction

6 months after dose reduction

P values

Body weight (kg)

77.6 ± 21.5

76.3 ± 20.9

0.015

Plasma glucose (mg/dL)

161 ± 71

163 ± 60

0.823

Hemoglobin A1c (%)

7.3 ± 1.5

7.4 ± 1.3

0.470

HDL-cholesterol (mg/dL)

54 ± 16

54 ± 14

0.744

LDL-cholesterol (mg/dL)

97 ± 23

101 ± 23

0.366

Triglyceride (mg/dL)

148 ± 142

149 ± 128

0.932

Aspartate aminotransferase (IU/L)

26 ± 19

24 ± 7

0.272

Alanine aminotransferase (IU/L)

27 ± 23

25 ± 12

0.457

Creatinine (mg/dL)

0.76 ± 0.25

0.966