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 9, September 2019, pages 651-663

Efficacy and Safety of Alogliptin in Elderly Patients With Type 2 Diabetes Mellitus

Figure 2. Changes in eGFR (all patients). *P < 0.05 versus 0 month, paired t-test; **P < 0.05, ANOVA. eGFR: estimated glomerular filtration rate; ANOVA: analysis of variance.

Figure 3. Changes in eGFR (patients newly receiving alogliptin). *P < 0.05 versus 0 month, paired t-test; **P < 0.05, ANOVA. eGFR: estimated glomerular filtration rate; ANOVA: analysis of variance.

**Table 1.** Baseline Characteristics
	Age < 65	Age 65 - 74	Age ≥ 75	P	Unknown
P < 0.05, Chi-square test (excluding “Unknown” cases); *P < 0.05, ANOVA. ANOVA: analysis of variance.
Male/female	75 (68.2%)/33 (30%)	46 (52.9%)/41 (47.1%)	42 (45.2%)/49 (52.7%)	0.009*	2 (1.8%)	0 (0%)	2 (2.2%)
Age	54.8 ± 7.9	69.7 ± 2.9	79.8 ± 3.8	< 0.001**	0 (0%)	0 (0%)	0 (0%)
Disease duration	7.5 ± 5.5	11.5 ± 7.9	13 ± 8.4	< 0.001**	44 (40%)	32 (36.8%)	40 (43%)
Diabetic retinopathy	6 (5.5%)	11 (12.6%)	6 (6.5%)	0.249	18 (16.4%)	14 (16.1%)	21 (22.6%)
Diabetic neuropathy	4 (3.6%)	9 (10.3%)	13 (14%)	0.089	18 (16.4%)	18 (20.7%)	17 (18.3%)
Diabetic nephropathy	12 (10.9%)	10 (11.5%)	12 (12.9%)	0.837	15 (13.6%)	16 (18.4%)	17 (18.3%)
Cerebrovascular disorders	5 (4.5%)	8 (9.2%)	8 (8.6%)	0.502	19 (17.3%)	15 (17.2%)	21 (22.6%)
Myocardial infarction	2 (1.8%)	7 (8%)	6 (6.5%)	0.223	19 (17.3%)	15 (17.2%)	21 (22.6%)
Angina pectoris	4 (3.6%)	13 (14.9%)	13 (14%)	0.029*	19 (17.3%)	14 (16.1%)	21 (22.6%)
Arteriosclerosis obliterans	2 (1.8%)	4 (4.6%)	4 (4.3%)	0.477	22 (20%)	20 (23%)	26 (28%)
Hypertension	54 (49.1%)	54 (62.1%)	60 (64.5%)	0.082	14 (12.7%)	12 (13.8%)	13 (14%)
Dyslipidemia	64 (58.2%)	54 (62.1%)	44 (47.3%)	0.327	14 (12.7%)	12 (13.8%)	16 (17.2%)
Hepatic steatosis	26 (23.6%)	16 (18.4%)	6 (6.5%)	0.016*	22 (20%)	23 (26.4%)	29 (31.2%)
Others	20 (18.2%)	27 (31%)	28 (30.1%)	0.192	30 (27.3%)	18 (20.7%)	24 (25.8%)
Smoking history	24 (21.8%)	22 (25.3%)	12 (12.9%)	0.283	42 (38.2%)	32 (36.8%)	43 (46.2%)
Drinking history	43 (39.1%)	29 (33.3%)	14 (15.1%)	0.005*	35 (31.8%)	30 (34.5%)	43 (46.2%)
Family history	29 (26.4%)	11 (12.6%)	9 (9.7%)	< 0.001*	51 (46.4%)	37 (42.5%)	61 (65.6%)
Compliance with exercise; good or fair	47 (42.7%)	48 (55.2%)	36 (38.7%)	0.232	51 (46.4%)	30 (34.5%)	46 (49.5%)
Compliance with diet therapy; good or fair	49 (44.5%)	47 (54%)	40 (43%)	0.325	49 (44.5%)	30 (34.5%)	46 (49.5%)

Table 1. Baseline Characteristics

Age < 65

Age 65 - 74

Age ≥ 75

Unknown

Age < 65

Age 65 - 74

Age ≥ 75

*P < 0.05, Chi-square test (excluding “Unknown” cases); **P < 0.05, ANOVA. ANOVA: analysis of variance.

Male/female

75 (68.2%)/33 (30%)

46 (52.9%)/41 (47.1%)

42 (45.2%)/49 (52.7%)

0.009*

2 (1.8%)

0 (0%)

2 (2.2%)

Age

54.8 ± 7.9

69.7 ± 2.9

79.8 ± 3.8

< 0.001**

0 (0%)

Disease duration

7.5 ± 5.5

11.5 ± 7.9

13 ± 8.4

< 0.001**

44 (40%)

32 (36.8%)

40 (43%)

Diabetic retinopathy

6 (5.5%)

11 (12.6%)

6 (6.5%)

0.249

18 (16.4%)

14 (16.1%)

21 (22.6%)

Diabetic neuropathy

4 (3.6%)

9 (10.3%)

13 (14%)

0.089

18 (16.4%)

18 (20.7%)

17 (18.3%)

Diabetic nephropathy

12 (10.9%)

10 (11.5%)

12 (12.9%)

0.837

15 (13.6%)

16 (18.4%)

17 (18.3%)

Cerebrovascular disorders

5 (4.5%)

8 (9.2%)

8 (8.6%)

0.502

19 (17.3%)

15 (17.2%)

21 (22.6%)

Myocardial infarction

2 (1.8%)

7 (8%)

6 (6.5%)

0.223

19 (17.3%)

15 (17.2%)

21 (22.6%)

Angina pectoris

4 (3.6%)

13 (14.9%)

13 (14%)

0.029*

19 (17.3%)

14 (16.1%)

21 (22.6%)

Arteriosclerosis obliterans

2 (1.8%)

4 (4.6%)

4 (4.3%)

0.477

22 (20%)

20 (23%)

26 (28%)

Hypertension

54 (49.1%)

54 (62.1%)

60 (64.5%)

0.082

14 (12.7%)

12 (13.8%)

13 (14%)

Dyslipidemia

64 (58.2%)

54 (62.1%)

44 (47.3%)

0.327

14 (12.7%)

12 (13.8%)

16 (17.2%)

Hepatic steatosis

26 (23.6%)

16 (18.4%)

6 (6.5%)

0.016*

22 (20%)

23 (26.4%)

29 (31.2%)

Others

20 (18.2%)

27 (31%)

28 (30.1%)

0.192

30 (27.3%)

18 (20.7%)

24 (25.8%)

Smoking history

24 (21.8%)

22 (25.3%)

12 (12.9%)

0.283

42 (38.2%)

32 (36.8%)

43 (46.2%)

Drinking history

43 (39.1%)

29 (33.3%)

14 (15.1%)

0.005*

35 (31.8%)

30 (34.5%)

43 (46.2%)

Family history

29 (26.4%)

11 (12.6%)

9 (9.7%)

< 0.001*

51 (46.4%)

37 (42.5%)

61 (65.6%)

Compliance with exercise; good or fair

47 (42.7%)

48 (55.2%)

36 (38.7%)

0.232

51 (46.4%)

30 (34.5%)

46 (49.5%)

Compliance with diet therapy; good or fair

49 (44.5%)

47 (54%)

40 (43%)

0.325

49 (44.5%)

30 (34.5%)

46 (49.5%)

**Table 2.** Medications of the Full Analysis Set
	Time	Age < 65	Age 65 - 74	Age ≥ 75	P*
DPP-4: dipeptidyl peptidase-4; M: month; N/A: not applicable. *P < 0.05 Chi-square test.
Number of applicable patients	0 M	110	87	93
12 M	100	79	84
DPP-4 inhibitors	Before	27 (24.5%)	28 (32.2%)	21 (22.6%)	0.302
0 M	110 (100%)	87 (100%)	93 (100%)	N/A
12 M	100 (100%)	79 (100%)	84 (100%)	N/A
Sulfonylurea	Before	38 (34.5%)	38 (43.7%)	41 (44.1%)	0.289
0 M	36 (32.7%)	38 (43.7%)	35 (37.6%)	0.289
12 M	40 (40%)	34 (43%)	32 (38.1%)	0.811
Biguanide	Before	36 (32.7%)	20 (23%)	14 (15.1%)	0.013*
0 M	39 (35.5%)	24 (27.6%)	14 (15.1%)	0.004*
12 M	50 (50%)	24 (30.4%)	17 (20.2%)	< 0.001*
Thiazolidine	Before	28 (25.5%)	12 (13.8%)	18 (19.4%)	0.125
0 M	22 (20%)	14 (16.1%)	16 (17.2%)	0.758
12M	22 (22%)	9 (11.4%)	15 (17.9%)	0.178
α-glucosidase inhibitors	Before	25 (22.7%)	20 (23%)	26 (28%)	0.639
0 M	19 (17.3%)	11 (12.6%)	15 (16.1%)	0.659
12 M	13 (13%)	10 (12.7%)	12 (14.3%)	0.948
Glinide	Before	5 (4.5%)	4 (4.6%)	7 (7.5%)	0.588
0 M	0 (0%)	0 (0%)	0 (0%)	N/A
12 M	0 (0%)	0 (0%)	0 (0%)	N/A
Insulin	Before	0 (0%)	1 (1.1%)	0 (0%)	0.310
0 M	0 (0%)	0 (0%)	0 (0%)	N/A
12 M	0 (0%)	0 (0%)	1 (1.2%)	0.343

Table 2. Medications of the Full Analysis Set

Time

Age < 65

Age 65 - 74

Age ≥ 75

DPP-4: dipeptidyl peptidase-4; M: month; N/A: not applicable. *P < 0.05 Chi-square test.

Number of applicable patients

0 M

110

12 M

100

DPP-4 inhibitors

Before

27 (24.5%)

28 (32.2%)

21 (22.6%)

0.302

0 M

110 (100%)

87 (100%)

93 (100%)

N/A

12 M

100 (100%)

79 (100%)

84 (100%)

N/A

Sulfonylurea

Before

38 (34.5%)

38 (43.7%)

41 (44.1%)

0.289

0 M

36 (32.7%)

38 (43.7%)

35 (37.6%)

0.289

12 M

40 (40%)

34 (43%)

32 (38.1%)

0.811

Biguanide

Before

36 (32.7%)

20 (23%)

14 (15.1%)

0.013*

0 M

39 (35.5%)

24 (27.6%)

14 (15.1%)

0.004*

12 M

50 (50%)

24 (30.4%)

17 (20.2%)

< 0.001*

Thiazolidine

Before

28 (25.5%)

12 (13.8%)

18 (19.4%)

0.125

0 M

22 (20%)

14 (16.1%)

16 (17.2%)

0.758

12M

22 (22%)

9 (11.4%)

15 (17.9%)

0.178

α-glucosidase inhibitors

Before

25 (22.7%)

20 (23%)

26 (28%)

0.639

0 M

19 (17.3%)

11 (12.6%)

15 (16.1%)

0.659

12 M

13 (13%)

10 (12.7%)

12 (14.3%)

0.948

Glinide

Before

5 (4.5%)

4 (4.6%)

7 (7.5%)

0.588

0 M

0 (0%)

N/A

12 M

0 (0%)

N/A

Insulin

Before

0 (0%)

1 (1.1%)

0 (0%)

0.310

0 M

0 (0%)

N/A

12 M

0 (0%)

1 (1.2%)

0.343

**Table 3.** Efficacy Endpoints in the Full Analysis Set
	Age < 65	Age 65 - 74	Age ≥ 75	P (ANOVA)
SD: standard deviation; ANOVA: analysis of variance; HbA1c: hemoglobin A1c; M: month; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; TG: triglyceride; GOT: glutamate oxaloacetate transaminase; GPT: glutamate pyruvate transaminase; γ-GTP: γ-glutamyl transpeptidase; SBP: systolic blood pressure; DBP: diastolic blood pressure; BMI: body mass index. P < 0.05 versus 0 month, paired t-test; *P < 0.05, ANOVA.
HbA1c (%)	0 M	110	7.65	1.32		87	7.39	1.15		93	7.06	1.02		0.002**
3 M	105	6.94	0.86		84	6.90	0.71		82	6.84	0.86		0.722
6 M	93	6.84	0.81		81	6.82	0.61		82	6.64	0.71		0.132
9 M	92	6.92	0.98		71	6.80	0.67		79	6.68	0.77		0.186
12 M	96	6.90	1.07		76	6.82	0.68		76	6.74	0.81		0.513
Δ3 M	105	-0.73	1.02	< 0.001*	84	-0.50	0.95	< 0.001*	82	-0.30	0.90	0.004*	0.010**
Δ6 M	93	-0.82	1.18	< 0.001*	81	-0.50	0.97	< 0.001*	82	-0.49	1.05	< 0.001*	0.066
Δ9 M	92	-0.73	1.28	< 0.001*	71	-0.49	0.86	< 0.001*	79	-0.41	1.10	0.001*	0.155
Δ12 M	96	-0.74	1.45	< 0.001*	76	-0.47	1.02	< 0.001*	76	-0.42	1.11	0.002*	0.180
Blood glucose (fasting) (mg/dL)	0 M	37	162.0	57.7		27	140.1	35.9		29	142.7	35.8		0.111
3 M	32	134.7	30.8		23	151.0	48.9		20	125.6	27.3		0.073
6 M	26	126.8	30.3		23	130.1	26.8		21	132.7	22.7		0.756
9 M	29	139.3	39.7		21	138.1	39.7		21	124.1	23.0		0.287
12 M	30	132.1	48.4		19	129.8	34.0		17	134.1	35.5		0.955
Δ3 M	27	-32.9	46.6	0.001*	18	9.4	40.9	0.341	18	-15.9	30.1	0.039*	0.005**
Δ6 M	22	-23.4	37.4	0.008*	19	-16.4	30.2	0.029*	20	-18.1	22.6	0.002*	0.749
Δ9 M	24	-25.3	56.3	0.038*	18	-10.0	29.3	0.166	18	-26.9	36.8	0.006*	0.437
Δ12 M	25	-39.6	66.8	0.007*	17	-17.7	23.9	0.008*	17	-13.7	38.0	0.157	0.197
Blood glucose (postprandial) (mg/dL)	0 M	42	189.4	63.8		38	180.3	63.6		37	188.9	78.2		0.810
3 M	39	162.3	55.0		33	147.4	31.9		34	165.2	45.2		0.233
6 M	42	162.5	71.3		32	161.2	47.6		33	162.0	55.9		0.996
9 M	36	161.9	58.7		29	154.	38.5		28	176.7	61.9		0.282
12 M	40	182.8	75.5		37	160.9	44.4		36	168.9	56.5		0.278
Δ3 M	35	-20.7	50.4	0.021*	30	-29.2	63.2	0.017*	33	-7.5	51.9	0.415	0.291
Δ6 M	33	-24.4	44.0	0.003*	30	-1.7	58.6	0.872	31	-15.6	61.2	0.165	0.264
Δ9 M	31	-23.3	58.6	0.035*	26	-5.9	46.9	0.525	25	9.6	74.7	0.525	0.136
Δ12 M	36	-6.6	66.3	0.552	33	-18.1	69.6	0.145	33	-2.2	66.7	0.852	0.614
TC (mg/dL)	0 M	74	197.3	35.8		48	193.6	34.2		41	185.1	27.4		0.178
3 M	64	192.5	35.5		44	187.7	25.0		35	182.5	31.7		0.314
6 M	54	187.0	31.1		40	185.8	30.5		33	187.8	33.0		0.959
9 M	50	186.1	29.9		31	182.8	31.6		27	176.8	30.7		0.449
12 M	57	188.5	32.6		34	189.3	32.6		28	181.4	30.1		0.560
Δ3 M	63	-3.0	30.4	0.432	43	-5.8	23.2	0.111	32	0.3	28.7	0.961	0.654
Δ6 M	54	-11.4	38.4	0.033*	39	-9.4	26.1	0.031*	32	1.7	31.2	0.766	0.194
Δ9 M	49	-15.3	33.3	0.002*	31	-12.1	25.5	0.013*	26	-3.7	23.5	0.426	0.258
Δ12 M	55	-12.7	32.2	0.005*	34	-8.2	21.5	0.032*	27	-1.0	24.7	0.841	0.199
LDL-C (mg/dL)	0 M	76	119.1	30.3		68	109.9	30.5		66	108.5	24.2		0.055
3 M	65	113.8	27.0		63	107.2	28.2		46	105.1	24.3		0.187
6 M	60	109.3	28.9		54	108.1	29.3		50	104.8	25.7		0.697
9 M	50	106.3	22.8		44	103.6	24.7		41	104.3	28.1		0.865
12 M	59	110.2	26.8		52	106.4	24.3		47	103.3	23.3		0.361
Δ3 M	62	-6.5	31.5	0.109	62	-3.2	21.6	0.251	44	1.4	15.8	0.570	0.270
Δ6 M	57	-11.6	33.4	0.012*	53	-3.1	20.3	0.269	49	-3.7	20.8	0.222	0.164
Δ9 M	47	-15.9	31.4	0.001*	42	-7.9	27.0	0.064	40	-3.3	21.9	0.343	0.097
Δ12 M	56	-12.7	27.3	< 0.001*	52	-6.8	29.5	0.105	44	-4.1	21.5	0.208	0.252
HDL-C (mg/dL)	0 M	90	52.0	12.4		69	56.7	13.3		74	56.0	13.6		0.046**
3 M	80	52.4	12.2		66	56.2	14.4		53	55.0	14.2		0.207
6 M	73	51.7	11.8		54	56.0	12.6		55	57.8	15.0		0.025**
9 M	67	52.0	13.4		46	55.9	15.7		46	56.2	13.8		0.209
12 M	75	53.0	12.1		51	55.0	11.9		55	57.5	15.4		0.167
Δ3 M	78	0.9	7.3	0.278	64	-0.4	5.7	0.615	51	0.2	7.9	0.860	0.561
Δ6 M	70	1.8	7.6	0.057	54	-2.1	7.4	0.043*	55	1.7	8.0	0.127	0.011**
Δ9 M	63	0.3	7.8	0.772	45	-1.6	8.6	0.208	46	0.8	7.3	0.472	0.298
Δ12 M	71	1.6	8.3	0.110	51	-2.4	6.7	0.015*	53	0.9	7.9	0.427	0.017**
TG (mg/dL)	0 M	92	195.2	193.5		77	165.5	119.8		74	128.2	70.2		0.012**
3 M	82	177.4	247.6		74	153.1	101.4		55	133.3	89.8		0.328
6 M	74	177.9	136.1		63	148.0	93.1		57	123.3	77.4		0.017**
9 M	68	164.4	100.2		55	147.2	85.4		48	122.1	64.9		0.038**
12 M	76	154.2	78.3		61	149.5	91.5		56	123.7	62.5		0.073
Δ3 M	80	-4.4	209.1	0.850	73	-11.7	95.9	0.300	53	0.7	79.2	0.948	0.893
Δ6 M	73	-37.3	144.0	0.030*	63	-10.9	104.1	0.409	57	-1.4	74.5	0.885	0.175
Δ9 M	66	-49.1	152.1	0.011*	54	-14.3	85.8	0.227	48	1.2	52.6	0.874	0.046**
Δ12 M	72	-24.0	117.8	0.089	61	-7.5	82.3	0.470	54	2.7	61.9	0.748	0.268
GOT (IU/L)	0 M	78	31.6	21.3		69	26.2	12.9		69	24.8	11.7		0.028**
3 M	67	29.2	18.0		61	26.3	13.2		48	25.7	11.0		0.377
6 M	62	28.0	16.3		56	26.1	12.4		52	23.7	8.5		0.221
9 M	53	28.9	17.6		41	26.4	11.4		38	25.6	20.7		0.623
12 M	64	28.9	18.0		50	28.5	18.0		48	24.6	11.6		0.335
Δ3 M	65	-3.1	18.0	0.164	58	-0.4	9.7	0.766	46	-0.2	5.5	0.852	0.371
Δ6 M	57	-2.3	17.2	0.324	55	0.4	11.4	0.804	51	-1.9	8.2	0.097	0.507
Δ9 M	51	-3.0	15.2	0.159	40	0.3	12.4	0.889	38	1.5	9.4	0.321	0.219
Δ12 M	58	-3.8	19.4	0.145	50	2.5	15.6	0.258	47	-1.0	11.9	0.583	0.135
GPT (IU/L)	0 M	90	38.9	31.6		76	27.3	17.9		72	21.1	15.2		< 0.001**
3 M	81	34.5	24.0		70	25.5	18.2		54	20.8	14.6		< 0.001**
6 M	72	35.9	33.5		61	26.0	15.6		56	18.3	11.1		< 0.001**
9 M	65	32.4	20.6		49	26.1	15.5		43	21.2	14.0		0.005**
12 M	78	35.2	29.3		55	28.3	20.9		50	18.5	9.2		< 0.001**
Δ3 M	78	-5.4	19.6	0.017*	67	-1.2	12.7	0.438	51	-0.9	6.7	0.330	0.139
Δ6 M	68	-3.3	31.7	0.399	61	-0.1	11.2	0.964	53	-2.5	10.7	0.097	0.680
Δ9 M	62	-6.7	23.2	0.027*	47	0.0	10.5	0.978	41	0.9	7.8	0.461	0.036**
Δ12 M	72	-5.2	26.8	0.106	55	1.9	15.1	0.348	49	-2.5	12.3	0.166	0.148
γ-GTP (IU/L)	0 M	81	56.7	51.9		65	45.0	57.2		71	40.6	69.3		0.226
3 M	69	53.5	59.9		58	45.2	61.8		50	44.3	69.2		0.670
6 M	66	54.3	49.4		49	52.4	66.1		51	37.9	52.1		0.248
9 M	57	54.3	49.6		37	61.8	90.4		42	55.0	123.5		0.915
12 M	68	49.0	42.9		45	56.2	80.2		50	36.6	61.8		0.281
Δ3 M	66	-4.5	20.3	0.076	54	-0.1	19.5	0.972	49	-0.6	16.7	0.805	0.380
Δ6 M	61	-3.8	21.9	0.178	48	2.8	46.6	0.680	51	-5.7	35.6	0.256	0.451
Δ9 M	54	-3.4	23.9	0.302	34	6.4	70.9	0.602	42	10.3	49.9	0.188	0.363
Δ12 M	62	-5.1	27.7	0.151	44	4.0	65.0	0.682	50	0.7	67.8	0.945	0.680
Serum amylase (IU/L)	0 M	30	59.9	25.3		17	67.0	19.3		11	83.6	24.7		0.022**
3 M	21	64.9	23.0		15	72.1	20.1		11	88.6	23.5		0.023**
6 M	12	67.3	25.3		13	71.4	20.3		10	86.8	24.7		0.144
9 M	5	63.6	14.9		2	80.5	3.5		4	80.0	17.4		0.250
12 M	10	55.9	16.5		9	76.0	21.2		3	113.0	29.5		0.001**
Δ3 M	19	4.5	12.1	0.121	14	6.8	20.6	0.241	9	1.6	14.7	0.759	0.746
Δ6 M	12	8.0	9.7	0.016*	11	13.4	17.2	0.028*	7	1.4	14.8	0.807	0.229
Δ9 M	4	2.3	8.3	0.624	2	1.0	4.2	0.795	4	-4.8	27.0	0.749	0.860
Δ12 M	9	1.1	11.4	0.777	8	9.9	21.7	0.238	2	-8.5	31.8	0.770	0.392
Serum creatinine (mg/dL)	0 M	89	0.70	0.16		65	0.73	0.27		72	0.73	0.20		0.458
3 M	77	0.72	0.17		60	0.75	0.27		56	0.80	0.40		0.283
6 M	73	0.73	0.17		52	0.75	0.27		58	0.76	0.19		0.556
9 M	66	0.74	0.16		46	0.75	0.32		49	0.73	0.20		0.856
12 M	77	0.76	0.17		51	0.76	0.28		56	0.75	0.18		0.961
Δ3 M	74	0.04	0.08	< 0.001*	57	0.00	0.08	0.692	54	0.03	0.13	0.093	0.160
Δ6 M	69	0.03	0.08	0.002*	52	0.02	0.10	0.122	56	0.01	0.10	0.355	0.578
Δ9 M	62	0.04	0.07	< 0.001*	42	0.03	0.08	0.012*	48	0.01	0.10	0.378	0.157
Δ12 M	70	0.06	0.08	< 0.001*	50	0.02	0.08	0.045*	54	0.01	0.10	0.319	0.016**
SBP (mm Hg)	0 M	108	133.0	17.2		86	132.3	13.3		91	137.5	21.5		0.097
3 M	103	130.1	13.7		84	131.1	14.7		87	135.2	16.4		0.050
6 M	91	131.4	13.8		81	130.8	14.1		83	136.4	17.3		0.035**
9 M	85	131.3	13.4		73	131.2	12.8		80	134.0	15.4		0.359
12 M	94	132.0	17.0		75	130.6	11.3		81	134.8	17.9		0.244
Δ3 M	101	-2.6	15.2	0.094	83	-1.0	14.5	0.551	87	-2.7	18.1	0.171	0.731
Δ6 M	91	-1.4	14.7	0.352	80	-1.4	13.7	0.359	81	-1.4	18.6	0.498	1.000
Δ9 M	85	-2.0	15.6	0.244	72	-1.1	14.3	0.501	79	-3.8	21.1	0.117	0.634
Δ12 M	94	-1.0	16.5	0.567	74	-1.7	15.2	0.331	80	-4.2	20.8	0.074	0.465
DBP (mm Hg)	0 M	108	80.0	11.4		86	73.2	10.0		91	74.0	10.4		< 0.001**
3 M	103	78.4	11.7		84	74.3	9.6		87	72.6	9.6		< 0.001**
6 M	91	78.5	11.1		81	73.4	9.8		82	72.4	8.7		< 0.001**
9 M	84	79.5	11.3		73	72.4	9.0		80	71.9	9.6		< 0.001**
12 M	94	79.6	10.8		75	73.6	8.4		81	72.6	9.8		< 0.001**
Δ3 M	101	-1.4	9.4	0.132	83	1.4	9.3	0.164	87	-1.7	12.4	0.196	0.093
Δ6 M	91	-1.5	8.0	0.075	80	0.3	8.3	0.717	80	-1.6	11.3	0.211	0.325
Δ9 M	84	-0.7	10.8	0.558	72	-0.3	9.8	0.829	79	-1.9	11.4	0.132	0.594
Δ12 M	94	-0.4	9.2	0.688	74	0.2	9.9	0.861	80	-1.5	9.1	0.148	0.524
Body weight (kg)	0 M	104	73.05	14.71		77	62.58	10.49		85	57.56	10.47		< 0.001**
3 M	87	71.73	13.60		69	61.64	10.28		65	57.11	11.50		< 0.001**
6 M	79	72.59	13.93		65	61.26	10.18		66	56.50	11.29		< 0.001**
9 M	71	73.11	13.75		55	60.90	10.54		61	57.51	11.04		< 0.001**
12 M	80	74.61	15.12		62	61.63	10.50		64	57.47	10.69		< 0.001**
Δ3 M	86	-0.05	2.02	0.822	68	0.00	2.12	1.000	64	-0.39	1.50	0.042*	0.442
Δ6 M	79	0.05	2.59	0.864	64	0.25	4.19	0.638	64	-0.33	1.62	0.112	0.538
Δ9 M	71	0.01	2.40	0.985	54	-0.29	1.90	0.274	60	0.07	2.47	0.819	0.676
Δ12 M	80	0.59	3.15	0.101	61	-0.25	2.07	0.347	63	-0.36	2.63	0.284	0.072
BMI (kg/m²)	0 M	85	26.61	4.63		68	24.58	3.18		73	23.55	3.23		< 0.001**
3 M	69	26.38	4.21		60	24.26	3.17		54	23.14	3.43		< 0.001**
6 M	62	26.72	4.14		57	24.21	3.28		54	23.16	3.30		< 0.001**
9 M	53	26.68	3.87		49	23.79	3.21		50	23.58	3.15		< 0.001**
12 M	62	27.21	4.75		55	24.07	3.27		54	23.45	3.03		< 0.001**
Δ3 M	68	0.05	0.61	0.482	60	0.00	0.89	0.981	54	-0.19	0.65	0.037*	0.166
Δ6 M	62	0.07	0.96	0.588	57	0.16	1.80	0.511	53	-0.18	0.71	0.066	0.337
Δ9 M	53	0.05	0.90	0.669	49	-0.07	0.74	0.521	50	0.07	1.05	0.648	0.713
Δ12 M	62	0.23	1.16	0.115	55	-0.09	0.80	0.402	54	-0.15	1.15	0.329	0.101

Table 3. Efficacy Endpoints in the Full Analysis Set

Age < 65

Age 65 - 74

Age ≥ 75

P (ANOVA)

Mean

SD: standard deviation; ANOVA: analysis of variance; HbA1c: hemoglobin A1c; M: month; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; TG: triglyceride; GOT: glutamate oxaloacetate transaminase; GPT: glutamate pyruvate transaminase; γ-GTP: γ-glutamyl transpeptidase; SBP: systolic blood pressure; DBP: diastolic blood pressure; BMI: body mass index. *P < 0.05 versus 0 month, paired t-test; **P < 0.05, ANOVA.

HbA1c (%)

0 M

110

7.65

1.32

7.39

1.15

7.06

1.02

0.002**

3 M

105

6.94

0.86

6.90

0.71

6.84

0.86

0.722

6 M

6.84

0.81

6.82

0.61

6.64

0.71

0.132

9 M

6.92

0.98

6.80

0.67

6.68

0.77

0.186

12 M

6.90

1.07

6.82

0.68

6.74

0.81

0.513

Δ3 M

105

-0.73

1.02

< 0.001*

-0.50

0.95

< 0.001*

-0.30

0.90

0.004*

0.010**

Δ6 M

-0.82

1.18

< 0.001*

-0.50

0.97

< 0.001*

-0.49

1.05

< 0.001*

0.066

Δ9 M

-0.73

1.28

< 0.001*

-0.49

0.86

< 0.001*

-0.41

1.10

0.001*

0.155

Δ12 M

-0.74

1.45

< 0.001*

-0.47

1.02

< 0.001*

-0.42

1.11

0.002*

0.180

Blood glucose (fasting) (mg/dL)

0 M

162.0

57.7

140.1

35.9

142.7

35.8

0.111

3 M

134.7

30.8

151.0

48.9

125.6

27.3

0.073

6 M

126.8

30.3

130.1

26.8

132.7

22.7

0.756

9 M

139.3

39.7

138.1

39.7

124.1

23.0

0.287

12 M

132.1

48.4

129.8

34.0

134.1

35.5

0.955

Δ3 M

-32.9

46.6

0.001*

9.4

40.9

0.341

-15.9

30.1

0.039*

0.005**

Δ6 M

-23.4

37.4

0.008*

-16.4

30.2

0.029*

-18.1

22.6

0.002*

0.749

Δ9 M

-25.3

56.3

0.038*

-10.0

29.3

0.166

-26.9

36.8

0.006*

0.437

Δ12 M

-39.6

66.8

0.007*

-17.7

23.9

0.008*

-13.7

38.0

0.157

0.197

Blood glucose (postprandial) (mg/dL)

0 M

189.4

63.8

180.3

63.6

188.9

78.2

0.810

3 M

162.3

55.0

147.4

31.9

165.2

45.2

0.233

6 M

162.5

71.3

161.2

47.6

162.0

55.9

0.996

9 M

161.9

58.7

154.

38.5

176.7

61.9

0.282

12 M

182.8

75.5

160.9

44.4

168.9

56.5

0.278

Δ3 M

-20.7

50.4

0.021*

-29.2

63.2

0.017*

-7.5

51.9

0.415

0.291

Δ6 M

-24.4

44.0

0.003*

-1.7

58.6

0.872

-15.6

61.2

0.165

0.264

Δ9 M

-23.3

58.6

0.035*

-5.9

46.9

0.525

9.6

74.7

0.525

0.136

Δ12 M

-6.6

66.3

0.552

-18.1

69.6

0.145

-2.2

66.7

0.852

0.614

TC (mg/dL)

0 M

197.3

35.8

193.6

34.2

185.1

27.4

0.178

3 M

192.5

35.5

187.7

25.0

182.5

31.7

0.314

6 M

187.0

31.1

185.8

30.5

187.8

33.0

0.959

9 M

186.1

29.9

182.8

31.6

176.8

30.7

0.449

12 M

188.5

32.6

189.3

32.6

181.4

30.1

0.560

Δ3 M

-3.0

30.4

0.432

-5.8

23.2

0.111

0.3

28.7

0.961

0.654

Δ6 M

-11.4

38.4

0.033*

-9.4

26.1

0.031*

1.7

31.2

0.766

0.194

Δ9 M

-15.3

33.3

0.002*

-12.1

25.5

0.013*

-3.7

23.5

0.426

0.258

Δ12 M

-12.7

32.2

0.005*

-8.2

21.5

0.032*

-1.0

24.7

0.841

0.199

LDL-C (mg/dL)

0 M

119.1

30.3

109.9

30.5

108.5

24.2

0.055

3 M

113.8

27.0

107.2

28.2

105.1

24.3

0.187

6 M

109.3

28.9

108.1

29.3

104.8

25.7

0.697

9 M

106.3

22.8

103.6

24.7

104.3

28.1

0.865

12 M

110.2

26.8

106.4

24.3

103.3

23.3

0.361

Δ3 M

-6.5

31.5

0.109

-3.2

21.6

0.251

1.4

15.8

0.570

0.270

Δ6 M

-11.6

33.4

0.012*

-3.1

20.3

0.269

-3.7

20.8

0.222

0.164

Δ9 M

-15.9

31.4

0.001*

-7.9

27.0

0.064

-3.3

21.9

0.343

0.097

Δ12 M

-12.7

27.3

< 0.001*

-6.8

29.5

0.105

-4.1

21.5

0.208

0.252

HDL-C (mg/dL)

0 M

52.0

12.4

56.7

13.3

56.0

13.6

0.046**

3 M

52.4

12.2

56.2

14.4

55.0

14.2

0.207

6 M

51.7

11.8

56.0

12.6

57.8

15.0

0.025**

9 M

52.0

13.4

55.9

15.7

56.2

13.8

0.209

12 M

53.0

12.1

55.0

11.9

57.5

15.4

0.167

Δ3 M

0.9

7.3

0.278

-0.4

5.7

0.615

0.2

7.9

0.860

0.561

Δ6 M

1.8

7.6

0.057

-2.1

7.4

0.043*

1.7

8.0

0.127

0.011**

Δ9 M

0.3

7.8

0.772

-1.6

8.6

0.208

0.8

7.3

0.472

0.298

Δ12 M

1.6

8.3

0.110

-2.4

6.7

0.015*

0.9

7.9

0.427

0.017**

TG (mg/dL)

0 M

195.2

193.5

165.5

119.8

128.2

70.2

0.012**

3 M

177.4

247.6

153.1

101.4

133.3

89.8

0.328

6 M

177.9

136.1

148.0

93.1

123.3

77.4

0.017**

9 M

164.4

100.2

147.2

85.4

122.1

64.9

0.038**

12 M

154.2

78.3

149.5

91.5

123.7

62.5

0.073

Δ3 M

-4.4

209.1

0.850

-11.7

95.9

0.300

0.7

79.2

0.948

0.893

Δ6 M

-37.3

144.0

0.030*

-10.9

104.1

0.409

-1.4

74.5

0.885

0.175

Δ9 M

-49.1

152.1

0.011*

-14.3

85.8

0.227

1.2

52.6

0.874

0.046**

Δ12 M

-24.0

117.8

0.089

-7.5

82.3

0.470

2.7

61.9

0.748

0.268

GOT (IU/L)

0 M

31.6

21.3

26.2

12.9

24.8

11.7

0.028**

3 M

29.2

18.0

26.3

13.2

25.7

11.0

0.377

6 M

28.0

16.3

26.1

12.4

23.7

8.5

0.221

9 M

28.9

17.6

26.4

11.4

25.6

20.7

0.623

12 M

28.9

18.0

28.5

18.0

24.6

11.6

0.335

Δ3 M

-3.1

18.0

0.164

-0.4

9.7

0.766

-0.2

5.5

0.852

0.371

Δ6 M

-2.3

17.2

0.324

0.4

11.4

0.804

-1.9

8.2

0.097

0.507

Δ9 M

-3.0

15.2

0.159

0.3

12.4

0.889

1.5

9.4

0.321

0.219

Δ12 M

-3.8

19.4

0.145

2.5

15.6

0.258

-1.0

11.9

0.583

0.135

GPT (IU/L)

0 M

38.9

31.6

27.3

17.9

21.1

15.2

< 0.001**

3 M

34.5

24.0

25.5

18.2

20.8

14.6

< 0.001**

6 M

35.9

33.5

26.0

15.6

18.3

11.1

< 0.001**

9 M

32.4

20.6

26.1

15.5

21.2

14.0

0.005**

12 M

35.2

29.3

28.3

20.9

18.5

9.2

< 0.001**

Δ3 M

-5.4

19.6

0.017*

-1.2

12.7

0.438

-0.9

6.7

0.330

0.139

Δ6 M

-3.3

31.7

0.399

-0.1

11.2

0.964

-2.5

10.7

0.097

0.680

Δ9 M

-6.7

23.2

0.027*

0.0

10.5

0.978

0.9

7.8

0.461

0.036**

Δ12 M

-5.2

26.8

0.106

1.9

15.1

0.348

-2.5

12.3

0.166

0.148

γ-GTP (IU/L)

0 M

56.7

51.9

45.0

57.2

40.6

69.3

0.226

3 M

53.5

59.9

45.2

61.8

44.3

69.2

0.670

6 M

54.3

49.4

52.4

66.1

37.9

52.1

0.248

9 M

54.3

49.6

61.8

90.4

55.0

123.5

0.915

12 M

49.0

42.9

56.2

80.2

36.6

61.8

0.281

Δ3 M

-4.5

20.3

0.076

-0.1

19.5

0.972

-0.6

16.7

0.805

0.380

Δ6 M

-3.8

21.9

0.178

2.8

46.6

0.680

-5.7

35.6

0.256

0.451

Δ9 M

-3.4

23.9

0.302

6.4

70.9

0.602

10.3

49.9

0.188

0.363

Δ12 M

-5.1

27.7

0.151

4.0

65.0

0.682

0.7

67.8

0.945

0.680

Serum amylase (IU/L)

0 M

59.9

25.3

67.0

19.3

83.6

24.7

0.022**

3 M

64.9

23.0

72.1

20.1

88.6

23.5

0.023**

6 M

67.3

25.3

71.4

20.3

86.8

24.7

0.144

9 M

63.6

14.9

80.5

3.5

80.0

17.4

0.250

12 M

55.9

16.5

76.0

21.2

113.0

29.5

0.001**

Δ3 M

4.5

12.1

0.121

6.8

20.6

0.241

1.6

14.7

0.759

0.746

Δ6 M

8.0

9.7

0.016*

13.4

17.2

0.028*

1.4

14.8

0.807

0.229

Δ9 M

2.3

8.3

0.624

1.0

4.2

0.795

-4.8

27.0

0.749

0.860

Δ12 M

1.1

11.4

0.777

9.9

21.7

0.238

-8.5

31.8

0.770

0.392

Serum creatinine (mg/dL)

0 M

0.70

0.16

0.73

0.27

0.73

0.20

0.458

3 M

0.72

0.17

0.75

0.27

0.80

0.40

0.283

6 M

0.73

0.17

0.75

0.27

0.76

0.19

0.556

9 M

0.74

0.16

0.75

0.32

0.73

0.20

0.856

12 M

0.76

0.17

0.76

0.28

0.75

0.18

0.961

Δ3 M

0.04

0.08

< 0.001*

0.00

0.08

0.692

0.03

0.13

0.093

0.160

Δ6 M

0.03

0.08

0.002*

0.02

0.10

0.122

0.01

0.10

0.355

0.578

Δ9 M

0.04

0.07

< 0.001*

0.03

0.08

0.012*

0.01

0.10

0.378

0.157

Δ12 M

0.06

0.08

< 0.001*

0.02

0.08

0.045*

0.01

0.10

0.319

0.016**

SBP (mm Hg)

0 M

108

133.0

17.2

132.3

13.3

137.5

21.5

0.097

3 M

103

130.1

13.7

131.1

14.7

135.2

16.4

0.050

6 M

131.4

13.8

130.8

14.1

136.4

17.3

0.035**

9 M

131.3

13.4

131.2

12.8

134.0

15.4

0.359

12 M

132.0

17.0

130.6

11.3

134.8

17.9

0.244

Δ3 M

101

-2.6

15.2

0.094

-1.0

14.5

0.551

-2.7

18.1

0.171

0.731

Δ6 M

-1.4

14.7

0.352

-1.4

13.7

0.359

-1.4

18.6

0.498

1.000

Δ9 M

-2.0

15.6

0.244

-1.1

14.3

0.501

-3.8

21.1

0.117

0.634

Δ12 M

-1.0

16.5

0.567

-1.7

15.2

0.331

-4.2

20.8

0.074

0.465

DBP (mm Hg)

0 M

108

80.0

11.4

73.2

10.0

74.0

10.4

< 0.001**

3 M

103

78.4

11.7

74.3

9.6

72.6

9.6

< 0.001**

6 M

78.5

11.1

73.4

9.8

72.4

8.7

< 0.001**

9 M

79.5

11.3

72.4

9.0

71.9

9.6

< 0.001**

12 M

79.6

10.8

73.6

8.4

72.6

9.8

< 0.001**

Δ3 M

101

-1.4

9.4

0.132

1.4

9.3

0.164

-1.7

12.4

0.196

0.093

Δ6 M

-1.5

8.0

0.075

0.3

8.3

0.717

-1.6

11.3

0.211

0.325

Δ9 M

-0.7

10.8

0.558

-0.3

9.8

0.829

-1.9

11.4

0.132

0.594

Δ12 M

-0.4

9.2

0.688

0.2

9.9

0.861

-1.5

9.1

0.148

0.524

Body weight (kg)

0 M

104

73.05

14.71

62.58

10.49

57.56

10.47

< 0.001**

3 M

71.73

13.60

61.64

10.28

57.11

11.50

< 0.001**

6 M

72.59

13.93

61.26

10.18

56.50

11.29

< 0.001**

9 M

73.11

13.75

60.90

10.54

57.51

11.04

< 0.001**

12 M

74.61

15.12

61.63

10.50

57.47

10.69

< 0.001**

Δ3 M

-0.05

2.02

0.822

0.00

2.12

1.000

-0.39

1.50

0.042*

0.442

Δ6 M

0.05

2.59

0.864

0.25

4.19

0.638

-0.33

1.62

0.112

0.538

Δ9 M

0.01

2.40

0.985

-0.29

1.90

0.274

0.07

2.47

0.819

0.676

Δ12 M

0.59

3.15

0.101

-0.25

2.07

0.347

-0.36

2.63

0.284

0.072

BMI (kg/m²)

0 M

26.61

4.63

24.58

3.18

23.55

3.23

< 0.001**

3 M

26.38

4.21

24.26

3.17

23.14

3.43

< 0.001**

6 M

26.72

4.14

24.21

3.28

23.16

3.30

< 0.001**

9 M

26.68

3.87

23.79

3.21

23.58

3.15

< 0.001**

12 M

27.21

4.75

24.07

3.27

23.45

3.03

< 0.001**

Δ3 M

0.05

0.61

0.482

0.00

0.89

0.981

-0.19

0.65

0.037*

0.166

Δ6 M

0.07

0.96

0.588

0.16

1.80

0.511

-0.18

0.71

0.066

0.337

Δ9 M

0.05

0.90

0.669

-0.07

0.74

0.521

0.07

1.05

0.648

0.713

Δ12 M

0.23

1.16

0.115

-0.09

0.80

0.402

-0.15

1.15

0.329

0.101