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 2, February 2016, pages 130-140

Efficacy and Safety of Alogliptin in Patients With Type 2 Diabetes: Analysis of the ATTAK-J Study

**Table 1.** Baseline Characteristics of the Full Analysis Set (N = 303)
Item	Male, 170 (56.1%), mean ± SD	Female, 127 (41.9%), median (range)	Unknown, 6 (2.0%), N
At the start of administration
Age (years)	67.3 ± 11.9	69.0 (29 - 91)	290
Height (cm)	160.70 ± 9.93	161.00 (137.4 - 184.0)	235
Weight (kg)	64.814 ± 14.065	63.300 (37.10 - 130.00)	281
Body mass index (kg/m²)	24.98 ± 4.10	24.66 (16.3 - 41.5)	233
Systolic blood pressure (mm Hg)	135.2 ± 18.6	132.0 (98 - 213)	297
Diastolic blood pressure (mm Hg)	76.2 ± 11.5	76.0 (48 - 124)	297
Hemoglobin A1c (%)	7.37 ± 1.21	7.10 (4.8 - 11.9)	303
Blood glucose (fasting) (mg/dL)	152.4 ± 47.7	143.5 (77 - 339)	86
Blood glucose (postprandial) (mg/dL)	184.4 ± 66.4	176.0 (66 - 516)	105
Estimated duration of diabetes (years)	10.3 ± 7.6	9.0 (0 - 40)	176
	Yes	No	Unknown/no data
Family history	49 (16.2%)	94 (31.0%)	160 (52.8%)
Smoking history	58 (19.1%)	118 (38.9%)	127 (41.9%)
Alcohol history	86 (28.4%)	98 (32.3%)	119 (39.3%)
Complications
Diabetic retinopathy	23 (7.6%)	225 (74.3%)	55 (18.2%)
Diabetic neuropathy	26 (8.6%)	222 (73.3%)	55 (18.2%)
Diabetic nephropathy	34 (11.2%)	219 (72.3%)	50 (16.5%)
Cerebrovascular accident (cerebral infarction/cerebral hemorrhage)	21 (6.9%)	224 (73.9%)	58 (19.1%)
Myocardial infarction	17 (5.6%)	228 (75.2%)	58 (19.1%)
Angina	33 (10.9%)	213 (70.3%)	57 (18.8%)
Arteriosclerosis obliterans (lower limbs)	10 (3.3%)	222 (73.3%)	71 (23.4%)
Hypertension	180 (59.4%)	83 (27.4%)	40 (13.2%)
Dyslipidemia	169 (55.8%)	90 (29.7%)	44 (14.5%)
Fatty liver	49 (16.2%)	178 (58.7%)	76 (25.1%)
Others	76 (25.1%)	153 (50.5%)	74 (24.4%)

Table 1. Baseline Characteristics of the Full Analysis Set (N = 303)

Item

Male, 170 (56.1%), mean ± SD

Female, 127 (41.9%), median (range)

Unknown, 6 (2.0%), N

At the start of administration

Age (years)

67.3 ± 11.9

69.0 (29 - 91)

290

Height (cm)

160.70 ± 9.93

161.00 (137.4 - 184.0)

235

Weight (kg)

64.814 ± 14.065

63.300 (37.10 - 130.00)

281

Body mass index (kg/m²)

24.98 ± 4.10

24.66 (16.3 - 41.5)

233

Systolic blood pressure (mm Hg)

135.2 ± 18.6

132.0 (98 - 213)

297

Diastolic blood pressure (mm Hg)

76.2 ± 11.5

76.0 (48 - 124)

297

Hemoglobin A1c (%)

7.37 ± 1.21

7.10 (4.8 - 11.9)

303

Blood glucose (fasting) (mg/dL)

152.4 ± 47.7

143.5 (77 - 339)

Blood glucose (postprandial) (mg/dL)

184.4 ± 66.4

176.0 (66 - 516)

105

Estimated duration of diabetes (years)

10.3 ± 7.6

9.0 (0 - 40)

176

Yes

Unknown/no data

Family history

49 (16.2%)

94 (31.0%)

160 (52.8%)

Smoking history

58 (19.1%)

118 (38.9%)

127 (41.9%)

Alcohol history

86 (28.4%)

98 (32.3%)

119 (39.3%)

Complications

Diabetic retinopathy

23 (7.6%)

225 (74.3%)

55 (18.2%)

Diabetic neuropathy

26 (8.6%)

222 (73.3%)

55 (18.2%)

Diabetic nephropathy

34 (11.2%)

219 (72.3%)

50 (16.5%)

Cerebrovascular accident (cerebral infarction/cerebral hemorrhage)

21 (6.9%)

224 (73.9%)

58 (19.1%)

Myocardial infarction

17 (5.6%)

228 (75.2%)

58 (19.1%)

Angina

33 (10.9%)

213 (70.3%)

57 (18.8%)

Arteriosclerosis obliterans (lower limbs)

10 (3.3%)

222 (73.3%)

71 (23.4%)

Hypertension

180 (59.4%)

83 (27.4%)

40 (13.2%)

Dyslipidemia

169 (55.8%)

90 (29.7%)

44 (14.5%)

Fatty liver

49 (16.2%)

178 (58.7%)

76 (25.1%)

Others

76 (25.1%)

153 (50.5%)

74 (24.4%)

**Table 2.** Medications of the Full Analysis Set
	Assessment times (baseline = start of alogliptin treatment)
ACE: angiotensin-converting enzyme; ARB: angiotensin receptor blocker; DPP-4: dipeptidyl peptidase-4.
Patients receiving the study drug in the full analysis set	303 (100.0%)	303 (100.0%)	303 (100.0%)	290 (100.0%)	278 (100.0%)	275 (100.0%)
Antidiabetic drugs
Total	225 (74.3%)	303 (100.0%)	303 (100.0%)	290 (100.0%)	278 (100.0%)	275 (100.0%)
Alogliptin	-	303 (100.0%)	303 (100.0%)	290 (100.0%)	278 (100.0%)	275 (100.0%)
DPP-4 inhibitors	80 (26.4%)	0 (0.0%)	0 (0.0%)	0 (0.0%)	0 (0.0%)	0 (0.0%)
Glimepiride	94 (31.0%)	90 (29.7%)	95 (31.4%)	87 (30.0%)	81 (29.1%)	83 (30.2%)
Glibenclamide	10 (3.3%)	7 (2.3%)	7 (2.3%)	7 (2.4%)	7 (2.5%)	7 (2.5%)
Gliclazide	15 (5.0%)	13 (4.3%)	14 (4.6%)	16 (5.5%)	16 (5.8%)	17 (6.2%)
Metformin	73 (24.1%)	82 (27.1%)	91 (30.0%)	91 (31.4%)	93 (33.5%)	96 (34.9%)
Pioglitazone	59 (19.5%)	52 (17.2%)	60 (19.8%)	56 (19.3%)	50 (18.0%)	46 (16.7%)
α-Glucosidase inhibitors	75 (24.8%)	48 (15.8%)	48 (15.8%)	45 (15.5%)	40 (14.4%)	38 (13.8%)
Glinides	18 (5.9%)	1 (0.3%)	1 (0.3%)	1 (0.3%)	1 (0.4%)	1 (0.4%)
Insulin	1 (0.3%)	0 (0.0%)	0 (0.0%)	0 (0.0%)	1 (0.4%)	1 (0.4%)
Lipid-lowering agents
Total	133 (43.9%)	140 (46.2%)	145 (47.9%)	146 (50.3%)	144 (51.8%)	143 (52.0%)
Statins	116 (38.3%)	123 (40.6%)	129 (42.6%)	131 (45.2%)	130 (46.8%)	129 (46.9%)
Others	29 (9.6%)	29 (9.6%)	31 (10.2%)	31(10.7%)	31(11.2%)	32 (11.6%)
Antihypertensive agents
Total	168 (55.4%)	174 (57.4%)	177 (58.4%)	176 (60.7%)	171 (61.5%)	174 (63.3%)
ARB	122 (40.3%)	125 (41.3%)	127 (41.9%)	128 (44.1%)	124 (44.6%)	127 (46.2%)
Ca antagonists	113 (37.3%)	116 (38.3%)	119 (39.3%)	117 (40.3%)	116 (41.7%)	118 (42.9%)
Diuretics	22 (7.3%)	20 (6.6%)	23(7.6%)	23(7.9%)	21 (7.6%)	22 (8.0%)
ACE inhibitors	14 (4.6%)	15 (5.0%)	14 (4.6%)	13 (4.5%)	13 (4.7%)	13 (4.7%)
Renin inhibitors	4 (1.3%)	3 (1.0%)	0 (0.0%)	0 (0.0%)	0 (0.0%)	0 (0.0%)
α-blockers	8 (2.6%)	8 (2.6%)	10 (3.3%)	10 (3.4%)	10 (3.6%)	11 (4.0%)
β-blocker	6 (2.0%)	6 (2.0%)	7 (2.3%)	8 (2.8%)	8 (2.9%)	8 (2.9%)
αβ-blockers	11 (3.6%)	13 (4.3%)	13 (4.3%)	13 (4.5%)	12 (4.3%)	11 (4.0%)
Aldosterone blockers	3 (1.0%)	3 (1.0%)	4 (1.3%)	3(1.0%)	3 (1.1%)	3 (1.1%)
Others	0 (0.0%)	0 (0.0%)	0 (0.0%)	0 (0.0%)	0 (0.0%)	0 (0.0%)

Table 2. Medications of the Full Analysis Set

Assessment times (baseline = start of alogliptin treatment)

Before administration

Baseline

Month 3

Month 6

Month 9

Month 12

ACE: angiotensin-converting enzyme; ARB: angiotensin receptor blocker; DPP-4: dipeptidyl peptidase-4.

Patients receiving the study drug in the full analysis set

303 (100.0%)

290 (100.0%)

278 (100.0%)

275 (100.0%)

Antidiabetic drugs

Total

225 (74.3%)

303 (100.0%)

290 (100.0%)

278 (100.0%)

275 (100.0%)

Alogliptin

303 (100.0%)

290 (100.0%)

278 (100.0%)

275 (100.0%)

DPP-4 inhibitors

80 (26.4%)

0 (0.0%)

Glimepiride

94 (31.0%)

90 (29.7%)

95 (31.4%)

87 (30.0%)

81 (29.1%)

83 (30.2%)

Glibenclamide

10 (3.3%)

7 (2.3%)

7 (2.4%)

7 (2.5%)

Gliclazide

15 (5.0%)

13 (4.3%)

14 (4.6%)

16 (5.5%)

16 (5.8%)

17 (6.2%)

Metformin

73 (24.1%)

82 (27.1%)

91 (30.0%)

91 (31.4%)

93 (33.5%)

96 (34.9%)

Pioglitazone

59 (19.5%)

52 (17.2%)

60 (19.8%)

56 (19.3%)

50 (18.0%)

46 (16.7%)

α-Glucosidase inhibitors

75 (24.8%)

48 (15.8%)

45 (15.5%)

40 (14.4%)

38 (13.8%)

Glinides

18 (5.9%)

1 (0.3%)

1 (0.4%)

Insulin

1 (0.3%)

0 (0.0%)

1 (0.4%)

Lipid-lowering agents

Total

133 (43.9%)

140 (46.2%)

145 (47.9%)

146 (50.3%)

144 (51.8%)

143 (52.0%)

Statins

116 (38.3%)

123 (40.6%)

129 (42.6%)

131 (45.2%)

130 (46.8%)

129 (46.9%)

Others

29 (9.6%)

31 (10.2%)

31(10.7%)

31(11.2%)

32 (11.6%)

Antihypertensive agents

Total

168 (55.4%)

174 (57.4%)

177 (58.4%)

176 (60.7%)

171 (61.5%)

174 (63.3%)

ARB

122 (40.3%)

125 (41.3%)

127 (41.9%)

128 (44.1%)

124 (44.6%)

127 (46.2%)

Ca antagonists

113 (37.3%)

116 (38.3%)

119 (39.3%)

117 (40.3%)

116 (41.7%)

118 (42.9%)

Diuretics

22 (7.3%)

20 (6.6%)

23(7.6%)

23(7.9%)

21 (7.6%)

22 (8.0%)

ACE inhibitors

14 (4.6%)

15 (5.0%)

14 (4.6%)

13 (4.5%)

13 (4.7%)

Renin inhibitors

4 (1.3%)

3 (1.0%)

0 (0.0%)

α-blockers

8 (2.6%)

10 (3.3%)

10 (3.4%)

10 (3.6%)

11 (4.0%)

β-blocker

6 (2.0%)

7 (2.3%)

8 (2.8%)

8 (2.9%)

αβ-blockers

11 (3.6%)

13 (4.3%)

13 (4.5%)

12 (4.3%)

11 (4.0%)

Aldosterone blockers

3 (1.0%)

4 (1.3%)

3(1.0%)

3 (1.1%)

Others

0 (0.0%)

**Table 3.** Multiple Regression Analysis of Changes in Hemoglobin A1c After 12 Months (Full Analysis Set)
Explanatory variables	Model 1: baseline characteristics (N = 110)	Model 2: baseline characteristics + concurrent treatment (N = 76)
*P < 0.050.
Baseline characteristics
Gender (female = 0; male = 1)	0.0213	0.1683	-0.3125	0.3551	0.8996	-0.0983	0.1833	-0.4645	0.2679	0.5935
Age (years)	-0.0107	0.0083	-0.0271	0.0056	0.1963	-0.0168	0.0092	-0.0352	0.0015	0.0718
Duration of diabetes (years)	0.0366	0.0113	0.0143	0.0589	0.0015*	0.0156	0.0134	-0.0112	0.0425	0.2490
Hemoglobin A1c (%)	-0.8660	0.0729	-1.0106	-0.7214	< 0.0001*	-0.9264	0.0749	-1.0761	-0.7767	< 0.0001*
Body mass index (kg/m²)	0.0001	0.0243	-0.0481	0.0482	0.9983	-0.0207	0.0244	-0.0695	0.0281	0.4007
Use of concomitant drugs in month 12: no = 0; yes = 1
Sulfonylureas						0.4211	0.1897	0.0420	0.8001	0.0300*
Biguanides						0.2787	0.1911	-0.1030	0.6605	0.1496
Thiazolidinediones						-0.1891	0.2282	-0.6450	0.2667	0.4102
α-Glucosidase inhibitors						-0.1456	0.2218	-0.5887	0.2976	0.5140
Compliance with concurrent treatment in month 12: poor = 0; fair or good = 1
Diet therapy						-1.2210	0.3144	-1.8490	-0.5929	0.0002*
Exercise therapy						-0.4497	0.2735	-0.9961	0.0968	0.1051

Table 3. Multiple Regression Analysis of Changes in Hemoglobin A1c After 12 Months (Full Analysis Set)

Explanatory variables

Model 1: baseline characteristics (N = 110)

Model 2: baseline characteristics + concurrent treatment (N = 76)

Estimate

Standard error

95% confidence interval

P value

Estimate

Standard error

95% confidence interval

P value

Lower limit

Upper limit

Lower limit

Upper limit

*P < 0.050.

Baseline characteristics

Gender (female = 0; male = 1)

0.0213

0.1683

-0.3125

0.3551

0.8996

-0.0983

0.1833

-0.4645

0.2679

0.5935

Age (years)

-0.0107

0.0083

-0.0271

0.0056

0.1963

-0.0168

0.0092

-0.0352

0.0015

0.0718

Duration of diabetes (years)

0.0366

0.0113

0.0143

0.0589

0.0015*

0.0156

0.0134

-0.0112

0.0425

0.2490

Hemoglobin A1c (%)

-0.8660

0.0729

-1.0106

-0.7214

< 0.0001*

-0.9264

0.0749

-1.0761

-0.7767

< 0.0001*

Body mass index (kg/m²)

0.0001

0.0243

-0.0481

0.0482

0.9983

-0.0207

0.0244

-0.0695

0.0281

0.4007

Use of concomitant drugs in month 12: no = 0; yes = 1

Sulfonylureas

0.4211

0.1897

0.0420

0.8001

0.0300*

Biguanides

0.2787

0.1911

-0.1030

0.6605

0.1496

Thiazolidinediones

-0.1891

0.2282

-0.6450

0.2667

0.4102

α-Glucosidase inhibitors

-0.1456

0.2218

-0.5887

0.2976

0.5140

Compliance with concurrent treatment in month 12: poor = 0; fair or good = 1

Diet therapy

-1.2210

0.3144

-1.8490

-0.5929

0.0002*

Exercise therapy

-0.4497

0.2735

-0.9961

0.0968

0.1051

**Table 4.** Efficacy Endpoints in the Full Analysis Set: Blood Glucose, Body Mass Index, and Blood Pressure
Item	Time after starting alogliptin (months)	Measured values	Changes of measured values
‡Linear mixed-effects models (covariance structure = unstructured) were used and multiplicity was adjusted by the Dunnett-Hsu method. *P < 0.050. SD: standard deviation; SE: standard error.
Blood glucose (fasting) (mg/dL)	0	98	150.2	46.9	339	140.0	77	-	-	-	-	-
3	79	137.8	38.4	294	131.0	80	-11.07	5.08	-23.53	1.39	0.0954
6	71	131.4	27.9	204	130.0	72	-16.39	3.64	-25.34	-7.45	< 0.0001*
9	73	135.2	35.7	290	127.0	90	-15.26	4.77	-26.96	-3.56	0.0062*
12	68	133.6	41.9	315	123.5	84	-16.79	5.46	-30.19	-3.38	0.0092*
Blood glucose (postprandial) (mg/dL)	0	118	185.7	68.1	516	174.5	66	-	-	-	-	-
3	107	158.6	45.7	327	154.0	83	-23.27	5.50	-36.73	-9.81	0.0002*
6	108	161.7	59.5	364	147.5	71	-19.05	5.72	-33.05	-5.06	0.0040*
9	93	163.9	54.5	362	152.0	59	-14.31	6.66	-30.62	1.99	0.1009
12	114	170.6	60.9	413	155.0	76	-10.76	6.52	-26.70	5.19	0.2705
Body mass index (kg/m²)	0	230	25.04	4.08	41.5	24.67	16.3	-	-	-	-	-
3	187	24.76	4.02	39.8	24.40	15.6	-0.07	0.05	-0.20	0.07	0.5238
6	176	24.81	4.03	38.1	24.49	15.2	-0.02	0.09	-0.25	0.22	0.9992
9	155	24.71	3.80	39.2	24.47	15.0	0.04	0.08	-0.16	0.24	0.9572
12	175	25.00	4.19	43.6	24.73	15.0	0.00	0.09	-0.21	0.21	1.0000
Systolic blood pressure (mm Hg)	0	297	135.2	18.6	213	132.0	98	-	-	-	-	-
3	286	133.0	15.7	183	132.0	94	-2.15	0.94	-4.43	0.13	0.0704
6	265	133.7	16.2	197	132.0	98	-1.64	0.98	-4.02	0.74	0.2527
9	248	132.6	14.8	193	132.0	97	-2.60	1.09	-5.23	0.04	0.0546
12	261	133.0	16.1	211	132.0	90	-2.19	1.10	-4.85	0.47	0.1349
Diastolic blood pressure (mm Hg)	0	297	76.2	11.5	124	76.0	48	-	-	-	-	-
3	286	75.4	10.8	110	75.0	45	-0.64	0.63	-2.18	0.90	0.6896
6	264	74.9	10.4	112	75.0	43	-1.16	0.59	-2.60	0.27	0.1480
9	247	74.7	10.7	112	74.0	50	-1.47	0.68	-3.14	0.19	0.0994
12	261	75.4	10.4	102	75.0	50	-0.88	0.59	-2.31	0.56	0.3626

Table 4. Efficacy Endpoints in the Full Analysis Set: Blood Glucose, Body Mass Index, and Blood Pressure

Item

Time after starting alogliptin (months)

Measured values

Changes of measured values

Mean

Median

Maximum

Minimum

Point estimate

95% confidence interval

P value‡

Lower limit

Upper limit

‡Linear mixed-effects models (covariance structure = unstructured) were used and multiplicity was adjusted by the Dunnett-Hsu method. *P < 0.050. SD: standard deviation; SE: standard error.

Blood glucose (fasting) (mg/dL)

150.2

46.9

339

140.0

137.8

38.4

294

131.0

-11.07

5.08

-23.53

1.39

0.0954

131.4

27.9

204

130.0

-16.39

3.64

-25.34

-7.45

< 0.0001*

135.2

35.7

290

127.0

-15.26

4.77

-26.96

-3.56

0.0062*

133.6

41.9

315

123.5

-16.79

5.46

-30.19

-3.38

0.0092*

Blood glucose (postprandial) (mg/dL)

118

185.7

68.1

516

174.5

107

158.6

45.7

327

154.0

-23.27

5.50

-36.73

-9.81

0.0002*

108

161.7

59.5

364

147.5

-19.05

5.72

-33.05

-5.06

0.0040*

163.9

54.5

362

152.0

-14.31

6.66

-30.62

1.99

0.1009

114

170.6

60.9

413

155.0

-10.76

6.52

-26.70

5.19

0.2705

Body mass index (kg/m²)

230

25.04

4.08

41.5

24.67

16.3

187

24.76

4.02

39.8

24.40

15.6

-0.07

0.05

-0.20

0.07

0.5238

176

24.81

4.03

38.1

24.49

15.2

-0.02

0.09

-0.25

0.22

0.9992

155

24.71

3.80

39.2

24.47

15.0

0.04

0.08

-0.16

0.24

0.9572

175

25.00

4.19

43.6

24.73

15.0

0.00

0.09

-0.21

0.21

1.0000

Systolic blood pressure (mm Hg)

297

135.2

18.6

213

132.0

286

133.0

15.7

183

132.0

-2.15

0.94

-4.43

0.13

0.0704

265

133.7

16.2

197

132.0

-1.64

0.98

-4.02

0.74

0.2527

248

132.6

14.8

193

132.0

-2.60

1.09

-5.23

0.04

0.0546

261

133.0

16.1

211

132.0

-2.19

1.10

-4.85

0.47

0.1349

Diastolic blood pressure (mm Hg)

297

76.2

11.5

124

76.0

286

75.4

10.8

110

75.0

-0.64

0.63

-2.18

0.90

0.6896

264

74.9

10.4

112

75.0

-1.16

0.59

-2.60

0.27

0.1480

247

74.7

10.7

112

74.0

-1.47

0.68

-3.14

0.19

0.0994

261

75.4

10.4

102

75.0

-0.88

0.59

-2.31

0.56

0.3626

**Table 5.** Efficacy Endpoints in the Full Analysis Set: Liver Function and Kidney Function
Item	Time after starting alogliptin (months)	Measured values	Changes of measured values
‡Linear mixed-effects models (covariance structure = unstructured) were used and multiplicity was adjusted by the Dunnett-Hsu method. *P < 0.050. eGFR: estimated glomerular filtration rate; γ-GTP: γ-glutamyl transpeptidase; GOT: glutamate oxaloacetate transaminase; GTP: glutamate pyruvate transaminase; SD: standard deviation; SE: standard error.
GOT (IU/L)	0	217	27.8	16.4	136	22.0	11	-	-	-	-	-
3	176	27.2	14.8	112	22.0	12	-1.32	0.86	-3.41	0.77	0.3332
6	171	26.1	13.1	97	21.0	11	-1.21	1.01	-3.68	1.26	0.5509
9	132	27.2	16.9	143	23.0	11	-0.06	1.03	-2.58	2.47	1.0000
12	164	27.5	16.3	122	23.0	12	0.16	1.21	-2.79	3.12	0.9997
GPT (IU/L)	0	239	29.8	24.5	179	21.0	6	-	-	-	-	-
3	205	27.8	20.7	138	20.0	6	-2.48	0.99	-4.91	-0.06	0.0432*
6	190	27.5	24.2	237	20.0	5	-2.27	1.48	-5.90	1.36	0.3482
9	157	27.4	17.9	109	21.0	8	-2.04	1.13	-4.82	0.74	0.2160
12	185	28.5	23.6	188	21.0	8	-1.77	1.37	-5.14	1.60	0.5063
γ-GTP (IU/L)	0	218	47.9	59.6	467	30.0	9	-	-	-	-	-
3	177	48.2	63.1	407	29.0	8	-1.83	1.40	-5.28	1.62	0.5098
6	166	48.7	55.8	365	30.0	8	-2.70	2.45	-8.75	3.34	0.6536
9	136	56.5	88.5	754	29.0	9	1.58	3.88	-8.00	11.17	0.9842
12	164	47.1	60.8	497	30.0	7	-1.55	3.83	-11.02	7.92	0.9846
Serum creatinine (mg/dL)	0	227	0.719	0.208	1.970	0.69	0.33	-	-	-	-	-
3	193	0.753	0.283	3.23	0.730	0.31	0.023	0.007	0.006	0.041	0.0052*
6	184	0.747	0.211	1.83	0.720	0.40	0.025	0.007	0.009	0.042	0.0008*
9	161	0.738	0.228	2.10	0.720	0.33	0.025	0.007	0.009	0.042	0.0005*
12	186	0.759	0.207	1.99	0.730	0.34	0.031	0.006	0.015	0.047	< 0.0001*
eGFR (mL/min/1.73 m²)	0	224	79.94	20.22	150.3	78.67	23.5	-	-	-	-	-
3	192	77.79	22.5	220.1	76.09	15.6	-2.16	0.87	-4.28	-0.03	0.0451*
6	181	76.48	18.66	129.4	74.24	29.2	-3.06	0.76	-4.92	-1.20	0.0003*
9	160	78.96	19.89	159.7	78.60	25.1	-2.16	0.80	-4.12	-0.19	0.0263*
12	183	75.78	18.95	155.5	74.16	26.7	-3.50	0.77	-5.41	-1.60	< 0.0001*

Table 5. Efficacy Endpoints in the Full Analysis Set: Liver Function and Kidney Function

Item

Time after starting alogliptin (months)

Measured values

Changes of measured values

Mean

Median

Maximum

Minimum

Point estimate

95% confidence interval

P value‡

Lower limit

Upper limit

‡Linear mixed-effects models (covariance structure = unstructured) were used and multiplicity was adjusted by the Dunnett-Hsu method. *P < 0.050. eGFR: estimated glomerular filtration rate; γ-GTP: γ-glutamyl transpeptidase; GOT: glutamate oxaloacetate transaminase; GTP: glutamate pyruvate transaminase; SD: standard deviation; SE: standard error.

GOT (IU/L)

217

27.8

16.4

136

22.0

176

27.2

14.8

112

22.0

-1.32

0.86

-3.41

0.77

0.3332

171

26.1

13.1

21.0

-1.21

1.01

-3.68

1.26

0.5509

132

27.2

16.9

143

23.0

-0.06

1.03

-2.58

2.47

1.0000

164

27.5

16.3

122

23.0

0.16

1.21

-2.79

3.12

0.9997

GPT (IU/L)

239

29.8

24.5

179

21.0

205

27.8

20.7

138

20.0

-2.48

0.99

-4.91

-0.06

0.0432*

190

27.5

24.2

237

20.0

-2.27

1.48

-5.90

1.36

0.3482

157

27.4

17.9

109

21.0

-2.04

1.13

-4.82

0.74

0.2160

185

28.5

23.6

188

21.0

-1.77

1.37

-5.14

1.60

0.5063

γ-GTP (IU/L)

218

47.9

59.6

467

30.0

177

48.2

63.1

407

29.0

-1.83

1.40

-5.28

1.62

0.5098

166

48.7

55.8

365

30.0

-2.70

2.45

-8.75

3.34

0.6536

136

56.5

88.5

754

29.0

1.58

3.88

-8.00

11.17

0.9842

164

47.1

60.8

497

30.0

-1.55

3.83

-11.02

7.92

0.9846

Serum creatinine (mg/dL)

227

0.719

0.208

1.970

0.69

0.33

193

0.753

0.283

3.23

0.730

0.31

0.023

0.007

0.006

0.041

0.0052*

184

0.747

0.211

1.83

0.720

0.40

0.025

0.007

0.009

0.042

0.0008*

161

0.738

0.228

2.10

0.720

0.33

0.025

0.007

0.009

0.042

0.0005*

186

0.759

0.207

1.99

0.730

0.34

0.031

0.006

0.015

0.047

< 0.0001*

eGFR (mL/min/1.73 m²)

224

79.94

20.22

150.3

78.67

23.5

192

77.79

22.5

220.1

76.09

15.6

-2.16

0.87

-4.28

-0.03

0.0451*

181

76.48

18.66

129.4

74.24

29.2

-3.06

0.76

-4.92

-1.20

0.0003*

160

78.96

19.89

159.7

78.60

25.1

-2.16

0.80

-4.12

-0.19

0.0263*

183

75.78

18.95

155.5

74.16

26.7

-3.50

0.77

-5.41

-1.60

< 0.0001*

**Table 6.** Efficacy Endpoints in the Full Analysis Set: Lipids and Serum Amylase
Item	Time after starting alogliptin (months)	Measured values	Changes of measured values
‡Linear mixed-effects models (covariance structure = unstructured) were used and multiplicity was adjusted by the Dunnett-Hsu method. *P < 0.050. HDL: high-density lipoprotein; LDL: low-density lipoprotein; SD: standard deviation; SE: standard error.
Total cholesterol (mg/dL)	0	163	193.2	33.6	301	191.0	127	-	-	-	-	-
3	143	188.6	31.7	326	186.0	113	-3.90	2.28	-9.49	1.69	0.2498
6	127	186.8	31.2	283	186.0	114	-5.98	2.81	-12.88	0.92	0.1082
9	108	182.8	30.5	252	182.5	105	-10.86	2.58	-17.20	-4.52	0.0002*
12	119	187.1	31.9	289	186.0	104	-6.84	2.48	-12.93	-0.74	0.0227*
LDL cholesterol (mg/dL)	0	211	112.91	28.85	208.0	113.00	50	-	-	-	-	-
3	174	109.13	26.88	198.0	108.00	47	-2.93	1.77	-7.26	1.40	0.2716
6	165	107.62	27.95	198.0	110.00	56	-5.56	1.91	-10.21	-0.91	0.0136*
9	135	104.84	24.95	163.0	104.00	48	-8.76	2.03	-13.70	-3.82	< 0.0001*
12	159	107.04	24.97	186.0	107.00	57	-7.22	1.95	-11.99	-2.46	0.0010*
HDL cholesterol (mg/dL)	0	234	54.60	13.15	96.0	53.00	29	-	-	-	-	-
3	199	54.34	13.52	100.0	52.00	27	0.20	0.49	-0.99	1.40	0.9826
6	183	54.73	13.26	96.0	53.00	26	0.45	0.56	-0.93	1.84	0.8432
9	159	54.31	14.26	98.0	52.00	26	0.06	0.61	-1.43	1.56	0.9999
12	182	54.90	13.16	96.0	53.00	31	0.46	0.57	-0.94	1.87	0.8413
Triglycerides (mg/dL)	0	244	165.3	144.1	1520	136.5	34	-	-	-	-	-
3	211	157.4	172.1	2190	124.0	32	-4.61	10.07	-29.23	20.00	0.9693
6	195	152.2	109.4	951	127.0	28	-15.25	7.45	-33.46	2.97	0.1288
9	171	147.0	87.9	619	124.0	27	-20.17	7.01	-37.31	-3.03	0.0151*
12	194	144.2	79.3	528	125.0	35	-16.50	7.20	-34.10	1.09	0.0730
Serum amylase (IU/L)	0	58	66.5	24.9	121	60.0	31	-	-	-	-	-
3	47	72.7	23.7	119	70.0	33	-	-	-	-	-
6	36	74.5	23.8	121	72.5	24	-	-	-	-	-
9	11	72.6	16.0	106	72.0	51	-	-	-	-	-
12	22	71.9	27.2	131	70.0	33	-	-	-	-	-

Table 6. Efficacy Endpoints in the Full Analysis Set: Lipids and Serum Amylase

Item

Time after starting alogliptin (months)

Measured values

Changes of measured values

Mean

Median

Maximum

Minimum

Point estimate

95% confidence interval

P value‡

Lower limit

Upper limit

‡Linear mixed-effects models (covariance structure = unstructured) were used and multiplicity was adjusted by the Dunnett-Hsu method. *P < 0.050. HDL: high-density lipoprotein; LDL: low-density lipoprotein; SD: standard deviation; SE: standard error.

Total cholesterol (mg/dL)

163

193.2

33.6

301

191.0

127

143

188.6

31.7

326

186.0

113

-3.90

2.28

-9.49

1.69

0.2498

127

186.8

31.2

283

186.0

114

-5.98

2.81

-12.88

0.92

0.1082

108

182.8

30.5

252

182.5

105

-10.86

2.58

-17.20

-4.52

0.0002*

119

187.1

31.9

289

186.0

104

-6.84

2.48

-12.93

-0.74

0.0227*

LDL cholesterol (mg/dL)

211

112.91

28.85

208.0

113.00

174

109.13

26.88

198.0

108.00

-2.93

1.77

-7.26

1.40

0.2716

165

107.62

27.95

198.0

110.00

-5.56

1.91

-10.21

-0.91

0.0136*

135

104.84

24.95

163.0

104.00

-8.76

2.03

-13.70

-3.82

< 0.0001*

159

107.04

24.97

186.0

107.00

-7.22

1.95

-11.99

-2.46

0.0010*

HDL cholesterol (mg/dL)

234

54.60

13.15

96.0

53.00

199

54.34

13.52

100.0

52.00

0.20

0.49

-0.99

1.40

0.9826

183

54.73

13.26

96.0

53.00

0.45

0.56

-0.93

1.84

0.8432

159

54.31

14.26

98.0

52.00

0.06

0.61

-1.43

1.56

0.9999

182

54.90

13.16

96.0

53.00

0.46

0.57

-0.94

1.87

0.8413

Triglycerides (mg/dL)

244

165.3

144.1

1520

136.5

211

157.4

172.1

2190

124.0

-4.61

10.07

-29.23

20.00

0.9693

195

152.2

109.4

951

127.0

-15.25

7.45

-33.46

2.97

0.1288

171

147.0

87.9

619

124.0

-20.17

7.01

-37.31

-3.03

0.0151*

194

144.2

79.3

528

125.0

-16.50

7.20

-34.10

1.09

0.0730

Serum amylase (IU/L)

66.5

24.9

121

60.0

72.7

23.7

119

70.0

74.5

23.8

121

72.5

72.6

16.0

106

72.0

71.9

27.2

131

70.0