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 11, Number 2, February 2019, pages 89-97

Investigation of a Dipeptidyl Peptidase-4 Inhibitor/Thiazolidinedione Combination Drug for Patients With Type 2 Diabetes and Poor Glycemic Control: Difficulty With Patient Enrollment

Figure 1. Study design (CHAT-LIO). CHAT: CHikushi Anti-Diabetes Mellitus Trial; LIO: LIOvel; DPP4I: dipeptidyl peptidase-4 inhibitor; HbA1c: hemoglobin A1c; DM: diabetes mellitus; PG: pioglitazone; AG: alogliptin.

Figure 2. Changes in BP and PR (n = 19). The changes in BP and PR during the study are presented. BP: blood pressure; SBP: systolic BP; DBP: diastolic BP; PR: pulse rate; bpm: beats per minute; NS: not significant; *: compared to the first point.

Figure 3. Specialties of doctors registered in previous studies of DPP4Is (CHAT-J, CHAT-N, and CHAT-T) and this study (CHAT-LIO). (a) Specialties of doctors registered in previous studies of DPP4Is (CHAT-J, CHAT-N, and CHAT-T) (n = 1,518). (b) Specialties of doctors registered in this study (CHAT-LIO) (n = 19).

Figure 4. Proportions of specialties of doctors prescribing DM drugs during 1 month at our hospital. (a) Percentage of doctors in each specialty prescribing DPP4Is (n = 456). (b) Percentage of doctors in each specialty prescribing SGLT2Is (n = 112). (c) Percentage of doctors in each specialty prescribing PG (n = 29). (d) Percentage of doctors in each specialty prescribing BGs (n = 236).

**Table 1.** Patient Characteristics at the First Point (n = 19)
n: number of patients; SD: standard deviation; BMI: body mass index.
Age, years, mean (SD)	61 (13)
Sex, male, n (%)	13 (68)
BMI, kg/m², mean (SD)	26.3 (4.5)
Hypertension, n (%)	12 (63)
Dyslipidemia, n (%)	9 (47)
Hyperuricemia, n (%)	2 (11)
Ischemic heart disease, n (%)	5 (26)
Cerebrovascular disease, n (%)	2 (11)
Smoking, n (%)	11 (61)
Drinking alcohol, n (%)	11 (61)
HbA1c (%)	8.2 (1.3)
Sulfonylurea, n (%)	9 (47)
Biguanide, n (%)	3 (16)
Alpha-glucosidase inhibitor, n (%)	1 (5)
Insulin, n (%)	0 (0)
Statin, n (%)	6 (32)
Fibrate, n (%)	1 (5)
Ezetimibe, n (%)	3 (16)

Table 1. Patient Characteristics at the First Point (n = 19)

n: number of patients; SD: standard deviation; BMI: body mass index.

Age, years, mean (SD)

61 (13)

Sex, male, n (%)

13 (68)

BMI, kg/m², mean (SD)

26.3 (4.5)

Hypertension, n (%)

12 (63)

Dyslipidemia, n (%)

9 (47)

Hyperuricemia, n (%)

2 (11)

Ischemic heart disease, n (%)

5 (26)

Cerebrovascular disease, n (%)

2 (11)

Smoking, n (%)

11 (61)

Drinking alcohol, n (%)

11 (61)

HbA1c (%)

8.2 (1.3)

Sulfonylurea, n (%)

9 (47)

Biguanide, n (%)

3 (16)

Alpha-glucosidase inhibitor, n (%)

1 (5)

Insulin, n (%)

0 (0)

Statin, n (%)

6 (32)

Fibrate, n (%)

1 (5)

Ezetimibe, n (%)

3 (16)

**Table 2.** DPP4Is Used by Patients at the First Point (n = 19)
	Dose (mg)	n
Alogliptin	25	4
Linagliptin	5	1
Sitagliptin	50	2
	100	3
Vildagliptin	100	9

Table 2. DPP4Is Used by Patients at the First Point (n = 19)

Dose (mg)

Alogliptin

Linagliptin

Sitagliptin

100

Vildagliptin

100

**Table 3.** Changes in BW and Laboratory Data (n = 19)
	First point	SD, IQR	Second point	SD, IQR	P value	Final point	SD, IQR	P value
BW: body weight; WBC: white blood cell count; Hb: hemoglobin; PLT: platelet count; Alb: albumin; T-bil: total bilirubin; AST: aspartate aminotransferase; ALT: alanine aminotransferase; LDH: lactate dehydrogenase; ALP: alkaline phosphatase; γ-GTP: γ-glutamyl transpeptidase; CK: creatine kinase; eGFR: estimated glomerular filtration rate; FBG: fasting blood glucose; HbA1c: hemoglobin A1c; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; TG: triglycerides; UA: uric acid; IQR: interquartile range; FIB-4: fibrosis-4.
BW, kg, mean (SD)	68.4	13.1	69.0	13.1	NS	68.0	13.2	NS
WBC, 10³/µL, mean (SD)	6,460	1,236	5,420	1,264	< 0.05	5,580	992	< 0.05
Hb, g/dL, mean (SD)	14.2	1.1	13.6	1.0	0.06	13.5	1.1	< 0.05
PLT, 10⁴/µL, mean (SD)	21.5	5.8	20.3	4.6	NS	21.6	5.8	NS
Alb, g/dL, mean (SD)	4.3	0.2	4.2	0.2	NS	4.2	0.3	NS
T-bil, mg/dL, mean (SD)	0.7	0.2	0.7	0.2	NS	0.6	0.2	< 0.05
AST, U/L, median (IQR)	36	26 - 51	30	23 - 35	< 0.05	29	23 - 31	< 0.01
ALT, U/L, median (IQR)	33	26 - 58	26	20 - 33	< 0.05	27	22 - 30	< 0.01
LDH, U/L, mean (SD)	200	34	220	29	< 0.005	216	31	NS
ALP, U/L, mean (SD)	230	48	202	43	0.09	190	32	0.07
γ-GTP, U/L, median (IQR)	43	25 - 71	24	20 - 48	< 0.05	23	19 - 44	< 0.01
CK, U/L, mean (SD)	116	42	146	75	NS	146	82	NS
eGFR, mL/min/1.73 m², mean (SD)	95	18	88	16	NS	76	16	0.096
FBG, mg/dL, mean (SD)	195	74	148	43	< 0.01	146	48	< 0.05
HbA1c, %, mean (SD)	8.2	1.3	7.4	1.1	< 0.05	7.3	1.1	0.06
LDL-C, mg/dL, mean (SD)	78	35	86	23	NS	80	20	NS
HDL-C, mg/dL, mean (SD)	54	14	60	13	< 0.01	54	13	NS
TG, mg/dL, median (IQR)	122	94 - 396	115	82 - 174	0.07	111	75 - 227	0.051
UA, mg/dL, mean (SD)	4.8	1.0	4.4	1.2	0.08	5.3	1.4	NS
FIB-4 index, mean (SD)	1.77	0.55	1.70	0.64	NS	1.81	0.82	NS

Table 3. Changes in BW and Laboratory Data (n = 19)

First point

SD, IQR

Second point

SD, IQR

P value

Final point

SD, IQR

P value

BW: body weight; WBC: white blood cell count; Hb: hemoglobin; PLT: platelet count; Alb: albumin; T-bil: total bilirubin; AST: aspartate aminotransferase; ALT: alanine aminotransferase; LDH: lactate dehydrogenase; ALP: alkaline phosphatase; γ-GTP: γ-glutamyl transpeptidase; CK: creatine kinase; eGFR: estimated glomerular filtration rate; FBG: fasting blood glucose; HbA1c: hemoglobin A1c; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; TG: triglycerides; UA: uric acid; IQR: interquartile range; FIB-4: fibrosis-4.

BW, kg, mean (SD)

68.4

13.1

69.0

13.1

68.0

13.2

WBC, 10³/µL, mean (SD)

6,460

1,236

5,420

1,264

< 0.05

5,580

992

< 0.05

Hb, g/dL, mean (SD)

14.2

1.1

13.6

1.0

0.06

13.5

1.1

< 0.05

PLT, 10⁴/µL, mean (SD)

21.5

5.8

20.3

4.6

21.6

5.8

Alb, g/dL, mean (SD)

4.3

0.2

4.2

0.2

4.2

0.3

T-bil, mg/dL, mean (SD)

0.7

0.2

0.7

0.2

0.6

0.2

< 0.05

AST, U/L, median (IQR)

26 - 51

23 - 35

< 0.05

23 - 31

< 0.01

ALT, U/L, median (IQR)

26 - 58

20 - 33

< 0.05

22 - 30

< 0.01

LDH, U/L, mean (SD)

200

220

< 0.005

216

ALP, U/L, mean (SD)

230

202

0.09

190

0.07

γ-GTP, U/L, median (IQR)

25 - 71

20 - 48

< 0.05

19 - 44

< 0.01

CK, U/L, mean (SD)

116

146

eGFR, mL/min/1.73 m², mean (SD)

0.096

FBG, mg/dL, mean (SD)

195

148

< 0.01

146

< 0.05

HbA1c, %, mean (SD)

8.2

1.3

7.4

1.1

< 0.05

7.3

1.1

0.06

LDL-C, mg/dL, mean (SD)

HDL-C, mg/dL, mean (SD)

< 0.01

TG, mg/dL, median (IQR)

122

94 - 396

115

82 - 174

0.07

111

75 - 227

0.051

UA, mg/dL, mean (SD)

4.8

1.0

4.4

1.2

0.08

5.3

1.4

FIB-4 index, mean (SD)

1.77

0.55

1.70

0.64

1.81

0.82

**Table 4.** Changes in Adherence to Medication (n = 19)
	First point	Second point	Final point	Wilcoxon singed-rank test among each point
NS: not significant.
Adherence (%)	82	94	78	NS

Table 4. Changes in Adherence to Medication (n = 19)

First point

Second point

Final point

Wilcoxon singed-rank test among each point

NS: not significant.

Adherence (%)