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 6, June 2016, pages 461-471

Factor Analysis of Changes in Hemoglobin A1c After 12 Months of Sitagliptin Therapy in Patients With Type 2 Diabetes

Figure 1. Changes in HbA1c. There was a significant decrease in HbA1c after 12 months of sitagliptin therapy in all three studies.

Figure 2. Changes in body weight. No significant change in body weight was seen after the start of sitagliptin therapy in all three studies.

Figure 3. Changes in eGFR. A significant decrease in eGFR was noted after the start of sitagliptin therapy in all three studies.

**Table 1.** Patient Characteristics
		1. ASSET-K specialist insulin, no	2. ASSIST-K specialist insulin, yes	3. ATTEST-K non-specialist	Comparison between groups: P value
*P < 0.05. SD: standard deviation; BMI: body mass index; HbA1c: hemoglobin A1c; NGSP: National Glycohemoglobin Standardization Program; eGFR: estimated glomerular filtration rate.
Statistical analysis set, n		1,074 (100.0%)	854 (100.0%)	411 (100.0%)
Sex	Male	605 (56.3%)	455 (53.3%)	224 (54.5%)	Chi-square test
Female	469 (43.7%)	399 (46.7%)	176 (42.8%)	0.181	0.909	0.367
Age at registration	Mean ± SD	63.1 ± 11.4	64.1 ± 11.9	68.0 ± 11.1	t-test
N	1,074	854	409	0.062	< 0.001*	< 0.001*
Complications of diabetes
Retinopathy	No	744 (69.3%)	460 (53.9%)	289 (70.3%)	Chi-square test
Yes	256 (23.8%)	294 (34.4%)	32 (7.8%)	< 0.001*	< 0.001*	< 0.001*
Neuropathy	No	686 (63.9%)	441 (51.6%)	344 (83.7%)	Chi-square test
Yes	299 (27.8%)	304 (35.6%)	30 (7.3%)	< 0.001*	< 0.001*	< 0.001*
Nephropathy	No	701 (65.3%)	410 (48.0%)	309 (75.2%)	Chi-square test
Yes	331 (30.8%)	342 (40.0%)	68 (16.5%)	< 0.001*	< 0.001*	< 0.001*
Arteriosclerotic disease
Cerebrovascular accident	No	976 (90.9%)	657 (76.9%)	361 (87.8%)	Chi-square test
Yes	64 (6.0%)	67 (7.8%)	41 (10.0%)	0.015*	0.008*	0.606
Myocardial infarction or angina	No	973 (90.6%)	585 (68.5%)	366 (89.1%)	Chi-square test
Yes	71 (6.6%)	144 (16.9%)	35 (8.5%)	< 0.001*	0.208	< 0.001*
Arteriosclerosis obliterans	No	1,020 (95.0%)	627 (73.4%)	388 (94.4%)	Chi-square test
Yes	23 (2.1%)	83 (9.7%)	10 (2.4%)	< 0.001*	0.727	< 0.001*
Other complications
Hypertension	No	548 (51.0%)	287 (33.6%)	110 (26.8%)	Chi-square test
Yes	526 (49.0%)	492 (57.6%)	297 (72.3%)	< 0.001*	< 0.001*	< 0.001*
Dyslipidemia	No	549 (51.1%)	240 (28.1%)	112 (27.3%)	Chi-square test
Yes	525 (48.9%)	543 (63.6%)	291 (70.8%)	< 0.001*	< 0.001*	0.307
Fatty liver	No	1,064 (99.1%)	383 (44.8%)	214 (52.1%)	Chi-square test
Yes	10 (0.9%)	280 (32.8%)	88 (21.4%)	< 0.001*	< 0.001*	< 0.001*
Smoking history	No	617 (57.4%)	390 (45.7%)	268 (65.2%)	Chi-square test
Yes	324 (30.2%)	216 (25.3%)	92 (22.4%)	0.625	0.002*	0.001*
Drinking history	No	562 (52.3%)	383 (44.8%)	221 (53.8%)	Chi-square test
Yes	386 (35.9%)	199 (23.3%)	137 (33.3%)	0.011*	0.420	0.205
Duration of diabetes, years	Mean ± SD	12.0 ± 7.9	17.1 ± 9.1	9.2 ± 7.4	t-test
N	987	722	242	< 0.001*	< 0.001*	< 0.001*
Body weight at the start of treatment	Mean ± SD	64.46 ± 13.86	66.17 ± 15.20	65.23 ± 13.25	t-test
N	1,062	853	387	0.011*	0.343	0.271
BMI at the start of treatment	Mean ± SD	24.66 ± 4.33	25.39 ± 4.52	25.31 ± 3.98	t-test
N	1,057	824	375	< 0.001*	0.012*	0.731
HbA1c at the start of treatment (NGSP, %)	Mean ± SD	7.99 ± 1.17	8.52 ± 1.34	7.75 ± 1.34	t-test
N	1,074	854	411	< 0.001*	0.002*	< 0.001*
eGFR at the start of treatment (mL/min/1.73 m²)	Mean ± SD	81.187 ± 22.180	75.885 ± 22.659	76.638 ± 19.555	t-test
N	792	625	348	< 0.001*	< 0.001*	0.587

Table 1. Patient Characteristics

1. ASSET-K
specialist insulin, no

2. ASSIST-K
specialist insulin, yes

3. ATTEST-K
non-specialist

Comparison between groups: P value

1 vs. 2

1 vs. 3

2 vs. 3

*P < 0.05. SD: standard deviation; BMI: body mass index; HbA1c: hemoglobin A1c; NGSP: National Glycohemoglobin Standardization Program; eGFR: estimated glomerular filtration rate.

Statistical analysis set, n

1,074 (100.0%)

854 (100.0%)

411 (100.0%)

Sex

Male

605 (56.3%)

455 (53.3%)

224 (54.5%)

Chi-square test

Female

469 (43.7%)

399 (46.7%)

176 (42.8%)

0.181

0.909

0.367

Age at registration

Mean ± SD

63.1 ± 11.4

64.1 ± 11.9

68.0 ± 11.1

t-test

1,074

854

409

0.062

< 0.001*

Complications of diabetes

Retinopathy

744 (69.3%)

460 (53.9%)

289 (70.3%)

Chi-square test

Yes

256 (23.8%)

294 (34.4%)

32 (7.8%)

< 0.001*

Neuropathy

686 (63.9%)

441 (51.6%)

344 (83.7%)

Chi-square test

Yes

299 (27.8%)

304 (35.6%)

30 (7.3%)

< 0.001*

Nephropathy

701 (65.3%)

410 (48.0%)

309 (75.2%)

Chi-square test

Yes

331 (30.8%)

342 (40.0%)

68 (16.5%)

< 0.001*

Arteriosclerotic disease

Cerebrovascular accident

976 (90.9%)

657 (76.9%)

361 (87.8%)

Chi-square test

Yes

64 (6.0%)

67 (7.8%)

41 (10.0%)

0.015*

0.008*

0.606

Myocardial infarction or angina

973 (90.6%)

585 (68.5%)

366 (89.1%)

Chi-square test

Yes

71 (6.6%)

144 (16.9%)

35 (8.5%)

< 0.001*

0.208

< 0.001*

Arteriosclerosis obliterans

1,020 (95.0%)

627 (73.4%)

388 (94.4%)

Chi-square test

Yes

23 (2.1%)

83 (9.7%)

10 (2.4%)

< 0.001*

0.727

< 0.001*

Other complications

Hypertension

548 (51.0%)

287 (33.6%)

110 (26.8%)

Chi-square test

Yes

526 (49.0%)

492 (57.6%)

297 (72.3%)

< 0.001*

Dyslipidemia

549 (51.1%)

240 (28.1%)

112 (27.3%)

Chi-square test

Yes

525 (48.9%)

543 (63.6%)

291 (70.8%)

< 0.001*

0.307

Fatty liver

1,064 (99.1%)

383 (44.8%)

214 (52.1%)

Chi-square test

Yes

10 (0.9%)

280 (32.8%)

88 (21.4%)

< 0.001*

Smoking history

617 (57.4%)

390 (45.7%)

268 (65.2%)

Chi-square test

Yes

324 (30.2%)

216 (25.3%)

92 (22.4%)

0.625

0.002*

0.001*

Drinking history

562 (52.3%)

383 (44.8%)

221 (53.8%)

Chi-square test

Yes

386 (35.9%)

199 (23.3%)

137 (33.3%)

0.011*

0.420

0.205

Duration of diabetes, years

Mean ± SD

12.0 ± 7.9

17.1 ± 9.1

9.2 ± 7.4

t-test

987

722

242

< 0.001*

Body weight at the start of treatment

Mean ± SD

64.46 ± 13.86

66.17 ± 15.20

65.23 ± 13.25

t-test

1,062

853

387

0.011*

0.343

0.271

BMI at the start of treatment

Mean ± SD

24.66 ± 4.33

25.39 ± 4.52

25.31 ± 3.98

t-test

1,057

824

375

< 0.001*

0.012*

0.731

HbA1c at the start of treatment (NGSP, %)

Mean ± SD

7.99 ± 1.17

8.52 ± 1.34

7.75 ± 1.34

t-test

1,074

854

411

< 0.001*

0.002*

< 0.001*

eGFR at the start of treatment (mL/min/1.73 m²)

Mean ± SD

81.187 ± 22.180

75.885 ± 22.659

76.638 ± 19.555

t-test

792

625

348

< 0.001*

0.587

**Table 2.** Use of Antidiabetic Drugs
	Antidiabetic drugs		1. ASSET-K specialist insulin, no	2. ASSIST-K specialist insulin, yes	3. ATTEST-K non-specialist	Comparison between groups: P value
*P < 0.05. SD: standard deviation.
Statistical analysis set, n			1,074 (100.0%)	854 (100.0%)	411 (100.0%)
Before administration of sitagliptin						Chi-square test
Insulin	Yes	0 (0.0%)	854 (100.0%)	9 (2.2%)	< 0.001*	< 0.001*	< 0.001*
Sulfonylureas	Yes	701 (65.3%)	191 (22.4%)	146 (35.5%)	< 0.001*	< 0.001*	< 0.001*
Biguanides	Yes	548 (51.0%)	354 (41.5%)	89 (21.7%)	< 0.001*	< 0.001*	< 0.001*
Thiazolidinediones	Yes	289 (26.9%)	92 (10.8%)	79 (19.2%)	< 0.001*	0.002*	< 0.001*
α-Glucosidase inhibitors	Yes	293 (27.3%)	227 (26.6%)	77 (18.7%)	0.731	< 0.001*	0.002*
Glinides	Yes	85 (7.9%)	15 (1.8%)	23 (5.6%)	< 0.001*	0.124	< 0.001*
Number of drugs	0	134 (12.5%)	0 (0.0%)	143 (34.8%)	Wilcoxon test
1	282 (26.3%)	300 (35.1%)	149 (36.3%)	< 0.001*	< 0.001*	< 0.001*
2	390 (36.3%)	298 (34.9%)	84 (20.4%)
3 or more	268 (25.0%)	256 (30.0%)	35 (8.5%)
Mean ± SD	1.8 ± 1.1	2.0 ± 1.0	1.0 ± 1.0
At the start of sitagliptin therapy	Sitagliptin dose (mg)	Mean ± SD	49.52 ± 6.60	46.42 ± 11.19	49.20 ± 14.34	Wilcoxon test
N	1,074	853	404	< 0.001*	< 0.001*	0.004*
					Chi-square test
Insulin	Yes	0 (0.0%)	853 (99.9%)	10 (2.4%)	< 0.001*	< 0.001*	< 0.001*
Sulfonylureas	Yes	688 (64.1%)	184 (21.5%)	153 (37.2%)	< 0.001*	< 0.001*	< 0.001*
Biguanides	Yes	521 (48.5%)	338 (39.6%)	93 (22.6%)	< 0.001*	< 0.001*	< 0.001*
Thiazolidinediones	Yes	255 (23.7%)	57 (6.7%)	53 (12.9%)	< 0.001*	< 0.001*	< 0.001*
α-Glucosidase inhibitors	Yes	102 (9.5%)	174 (20.4%)	41 (10.0%)	< 0.001*	0.78	< 0.001*
Glinides	Yes	24 (2.2%)	1 (0.1%)	0 (0.0%)	< 0.001*	0.002*	0.488
Number of concomitant medications	0	194 (18.1%)	1 (0.1%)	164 (39.9%)	Wilcoxon test
1	356 (33.1%)	350 (41.0%)	166 (40.4%)	< 0.001*	< 0.001*	< 0.001*
2	360 (33.5%)	289 (33.8%)	60 (14.6%)
3 or more	164 (15.3%)	214 (25.1%)	21 (5.1%)
Mean ± SD	1.5 ± 1.0	1.9 ± 0.9	0.9 ± 0.9
After 12 months of sitagliptin therapy	Sitagliptin dose (mg)	Mean ± SD	56.98 ± 18.66	52.22 ± 15.85	51.91 ± 15.55	Wilcoxon test
N	1,025	843	399	< 0.001*	< 0.001*	0.737
					Chi-square test
Insulin	Yes	0 (0.0%)	847 (99.2%)	11 (2.7%)	< 0.001*	< 0.001*	< 0.001*
Sulfonylureas	Yes	702 (65.4%)	165 (19.3%)	166 (40.4%)	< 0.001*	< 0.001*	< 0.001*
Biguanides	Yes	578 (53.8%)	285 (33.4%)	107 (26.0%)	< 0.001*	< 0.001*	0.008*
Thiazolidinediones	Yes	238 (22.2%)	61 (7.1%)	53 (12.9%)	< 0.001*	< 0.001*	< 0.001*
α-Glucosidase inhibitors	Yes	99 (9.2%)	174 (20.4%)	46 (11.2%)	< 0.001*	0.251	< 0.001*
Glinides	Yes	20 (1.9%)	0 (0.0%)	0 (0.0%)	< 0.001*	0.005*	Not testable
Number of concomitant medications	0	168 (15.6%)	5 (0.6%)	153 (37.2%)	Wilcoxon test
	1	355 (33.1%)	390 (45.7%)	161 (39.2%)	< 0.001*	< 0.001*	< 0.001*
	2	387 (36.0%)	262 (30.7%)	72 (17.5%)
	3 or more	164 (15.3%)	197 (23.1%)	25 (6.1%)
	Mean ± SD	1.5 ± 1.0	1.8 ± 0.9	0.9 ± 0.9

Table 2. Use of Antidiabetic Drugs

Antidiabetic drugs

1. ASSET-K
specialist insulin, no

2. ASSIST-K
specialist insulin, yes

3. ATTEST-K
non-specialist

Comparison between groups: P value

1 vs. 2

1 vs. 3

2 vs. 3

*P < 0.05. SD: standard deviation.

Statistical analysis set, n

1,074 (100.0%)

854 (100.0%)

411 (100.0%)

Before administration of sitagliptin

Chi-square test

Insulin

Yes

0 (0.0%)

854 (100.0%)

9 (2.2%)

< 0.001*

Sulfonylureas

Yes

701 (65.3%)

191 (22.4%)

146 (35.5%)

< 0.001*

Biguanides

Yes

548 (51.0%)

354 (41.5%)

89 (21.7%)

< 0.001*

Thiazolidinediones

Yes

289 (26.9%)

92 (10.8%)

79 (19.2%)

< 0.001*

0.002*

< 0.001*

α-Glucosidase inhibitors

Yes

293 (27.3%)

227 (26.6%)

77 (18.7%)

0.731

< 0.001*

0.002*

Glinides

Yes

85 (7.9%)

15 (1.8%)

23 (5.6%)

< 0.001*

0.124

< 0.001*

Number of drugs

134 (12.5%)

0 (0.0%)

143 (34.8%)

Wilcoxon test

282 (26.3%)

300 (35.1%)

149 (36.3%)

< 0.001*

390 (36.3%)

298 (34.9%)

84 (20.4%)

3 or more

268 (25.0%)

256 (30.0%)

35 (8.5%)

Mean ± SD

1.8 ± 1.1

2.0 ± 1.0

1.0 ± 1.0

At the start of sitagliptin therapy

Sitagliptin dose (mg)

Mean ± SD

49.52 ± 6.60

46.42 ± 11.19

49.20 ± 14.34

Wilcoxon test

1,074

853

404

< 0.001*

0.004*

Chi-square test

Insulin

Yes

0 (0.0%)

853 (99.9%)

10 (2.4%)

< 0.001*

Sulfonylureas

Yes

688 (64.1%)

184 (21.5%)

153 (37.2%)

< 0.001*

Biguanides

Yes

521 (48.5%)

338 (39.6%)

93 (22.6%)

< 0.001*

Thiazolidinediones

Yes

255 (23.7%)

57 (6.7%)

53 (12.9%)

< 0.001*

α-Glucosidase inhibitors

Yes

102 (9.5%)

174 (20.4%)

41 (10.0%)

< 0.001*

0.78

< 0.001*

Glinides

Yes

24 (2.2%)

1 (0.1%)

0 (0.0%)

< 0.001*

0.002*

0.488

Number of concomitant medications

194 (18.1%)

1 (0.1%)

164 (39.9%)

Wilcoxon test

356 (33.1%)

350 (41.0%)

166 (40.4%)

< 0.001*

360 (33.5%)

289 (33.8%)

60 (14.6%)

3 or more

164 (15.3%)

214 (25.1%)

21 (5.1%)

Mean ± SD

1.5 ± 1.0

1.9 ± 0.9

0.9 ± 0.9

After 12 months of sitagliptin therapy

Sitagliptin dose (mg)

Mean ± SD

56.98 ± 18.66

52.22 ± 15.85

51.91 ± 15.55

Wilcoxon test

1,025

843

399

< 0.001*

0.737

Chi-square test

Insulin

Yes

0 (0.0%)

847 (99.2%)

11 (2.7%)

< 0.001*

Sulfonylureas

Yes

702 (65.4%)

165 (19.3%)

166 (40.4%)

< 0.001*

Biguanides

Yes

578 (53.8%)

285 (33.4%)

107 (26.0%)

< 0.001*

0.008*

Thiazolidinediones

Yes

238 (22.2%)

61 (7.1%)

53 (12.9%)

< 0.001*

α-Glucosidase inhibitors

Yes

99 (9.2%)

174 (20.4%)

46 (11.2%)

< 0.001*

0.251

< 0.001*

Glinides

Yes

20 (1.9%)

0 (0.0%)

< 0.001*

0.005*

Not testable

Number of concomitant medications

168 (15.6%)

5 (0.6%)

153 (37.2%)

Wilcoxon test

355 (33.1%)

390 (45.7%)

161 (39.2%)

< 0.001*

387 (36.0%)

262 (30.7%)

72 (17.5%)

3 or more

164 (15.3%)

197 (23.1%)

25 (6.1%)

Mean ± SD

1.5 ± 1.0

1.8 ± 0.9

0.9 ± 0.9

**Table 3.** Factor Analysis of Changes in HbA1c After 12 Months
Explanatory variable	12-month change in HbA1c	Univariate model	Initial multivariate model (P < 0.05 in univariate model)	Final multivariate model (step-down method, P < 0.05)
*P < 0.05. Factors: study, sex, age (at registration), complications of diabetes (retinopathy, neuropathy, nephropathy), arteriosclerotic disease (cerebrovascular accident, myocardial infarction, angina, arteriosclerosis obliterans), smoking history, drinking history, duration of diabetes, body weight (at the start of treatment), BMI (at the start of treatment), HbA1c (at the start of treatment), and eGFR (at the start of treatment). HbA1c: hemoglobin A1c; SD: standard deviation; CI: confidence interval; NGSP: National Glycohemoglobin Standardization Program; eGFR: estimated glomerular filtration rate.
Intercept	2,339	-0.68	1.13	-	-	-	0.013	-0.155, 0.182	0.876	0.021	-0.111, 0.152	0.757
Study
ASSET-K	1,074	-0.68	1.08	Reference	-	(0.003*)	Reference	-	(< 0.001*)	Reference	-	(< 0.001*)
ASSIST-K	854	-0.61	1.20	0.070	-0.032, 0.171	0.178	0.284	0.190, 0.378	< 0.001*	0.286	0.193, 0.379	< 0.001*
ATTEST-K	411	-0.84	1.10	-0.165	-0.293, -0.036	0.012*	-0.182	-0.304, -0.060	0.003*	-0.193	-0.315, -0.071	0.002*
Age at registration
56 or younger	542	-0.71	1.43	Reference	-	(0.007*)	Reference	-	(< 0.001*)	Reference	-	(< 0.001*)
57 - 64	560	-0.79	1.09	-0.076	-0.209, 0.058	0.266	-0.236	-0.356, -0.116	< 0.001*	-0.234	-0.353, -0.115	< 0.001*
65 - 72	617	-0.65	0.93	0.067	-0.063, 0.197	0.315	-0.261	-0.384, -0.137	< 0.001*	-0.252	-0.371, -0.132	< 0.001*
73 or older	618	-0.60	1.02	0.115	-0.015, 0.245	0.082	-0.220	-0.351, -0.088	0.001*	-0.219	-0.342, -0.095	< 0.001*
Unknown	2	-2.40	2.55	-1.688	-3.253, -0.123	0.035*	-1.547	-2.919, -0.175	0.027*	-1.436	-2.806, -0.065	0.040*
Duration of diabetes (years)
Less than 10 years	713	-0.77	1.26	Reference	-	(< 0.001*)	Reference	-	(0.007*)	Reference	-	(0.007*)
10 - 19 years	758	-0.60	1.08	0.170	0.055, 0.285	0.004*	0.180	0.075, 0.285	< 0.001*	0.181	0.076, 0.286	< 0.001*
20 years or longer	480	-0.59	0.88	0.174	0.044, 0.304	0.009*	0.122	-0.004, 0.248	0.058	0.124	-0.002, 0.251	0.053
Unknown	388	-0.82	1.21	-0.055	-0.194, 0.084	0.438	0.039	-0.089, 0.167	0.547	0.046	-0.082, 0.174	0.482
HbA1c at the start of treatment (NGSP, %)
Less than 7.20	473	-0.11	0.72	Reference	-	(< 0.001*)	Reference	-	(< 0.001*)	Reference	-	(< 0.001*)
7.20 - 7.84	696	-0.40	0.67	-0.283	-0.401, -0.165	< 0.001*	-0.391	-0.509, -0.273	< 0.001*	-0.380	-0.498, -0.262	< 0.001*
7.85 - 8.79	577	-0.65	0.87	-0.533	-0.655, -0.411	< 0.001*	-0.697	-0.822, -0.572	< 0.001*	-0.691	-0.816, -0.567	< 0.001*
8.80 or higher	593	-1.51	1.53	-1.395	-1.516, -1.273	< 0.001*	-1.582	-1.708, -1.455	< 0.001*	-1.583	-1.709, -1.458	< 0.001*
eGFR at the start of treatment (mL/min/1.73 m²)
Less than 63.56	441	-0.66	1.03	Reference	-	(< 0.001*)	Reference	-	(0.094)
63.56 - 77.51	441	-0.64	0.88	0.017	-0.132, 0.165	0.827	-0.035	-0.166, 0.097	0.607
77.52 - 91.43	440	-0.67	1.04	-0.013	-0.162, 0.135	0.861	0.027	-0.107, 0.161	0.694
91.44 or higher	443	-0.91	1.56	-0.258	-0.406, -0.109	< 0.001*	-0.047	-0.189, 0.094	0.513
Unknown	574	-0.57	1.02	0.086	-0.053, 0.226	0.226	0.107	-0.020, 0.235	0.099

Table 3. Factor Analysis of Changes in HbA1c After 12 Months

Explanatory variable

12-month change in HbA1c

Univariate model

Initial multivariate model (P < 0.05 in univariate model)

Final multivariate model (step-down method, P < 0.05)

Mean

Point estimate

95% CI

Category P value (variable P value)

Point estimate

95% CI

Category P value (variable P value)

Point estimate

95% CI

Category P value (variable P value)

*P < 0.05. Factors: study, sex, age (at registration), complications of diabetes (retinopathy, neuropathy, nephropathy), arteriosclerotic disease (cerebrovascular accident, myocardial infarction, angina, arteriosclerosis obliterans), smoking history, drinking history, duration of diabetes, body weight (at the start of treatment), BMI (at the start of treatment), HbA1c (at the start of treatment), and eGFR (at the start of treatment). HbA1c: hemoglobin A1c; SD: standard deviation; CI: confidence interval; NGSP: National Glycohemoglobin Standardization Program; eGFR: estimated glomerular filtration rate.

Intercept

2,339

-0.68

1.13

0.013

-0.155, 0.182

0.876

0.021

-0.111, 0.152

0.757

Study

ASSET-K

1,074

-0.68

1.08

Reference

(0.003*)

Reference

(< 0.001*)

Reference

(< 0.001*)

ASSIST-K

854

-0.61

1.20

0.070

-0.032, 0.171

0.178

0.284

0.190, 0.378

< 0.001*

0.286

0.193, 0.379

< 0.001*

ATTEST-K

411

-0.84

1.10

-0.165

-0.293, -0.036

0.012*

-0.182

-0.304, -0.060

0.003*

-0.193

-0.315, -0.071

0.002*

Age at registration

56 or younger

542

-0.71

1.43

Reference

(0.007*)

Reference

(< 0.001*)

Reference

(< 0.001*)

57 - 64

560

-0.79

1.09

-0.076

-0.209, 0.058

0.266

-0.236

-0.356, -0.116

< 0.001*

-0.234

-0.353, -0.115

< 0.001*

65 - 72

617

-0.65

0.93

0.067

-0.063, 0.197

0.315

-0.261

-0.384, -0.137

< 0.001*

-0.252

-0.371, -0.132

< 0.001*

73 or older

618

-0.60

1.02

0.115

-0.015, 0.245

0.082

-0.220

-0.351, -0.088

0.001*

-0.219

-0.342, -0.095

< 0.001*

Unknown

-2.40

2.55

-1.688

-3.253, -0.123

0.035*

-1.547

-2.919, -0.175

0.027*

-1.436

-2.806, -0.065

0.040*

Duration of diabetes (years)

Less than 10 years

713

-0.77

1.26

Reference

(< 0.001*)

Reference

(0.007*)

Reference

(0.007*)

10 - 19 years

758

-0.60

1.08

0.170

0.055, 0.285

0.004*

0.180

0.075, 0.285

< 0.001*

0.181

0.076, 0.286

< 0.001*

20 years or longer

480

-0.59

0.88

0.174

0.044, 0.304

0.009*

0.122

-0.004, 0.248

0.058

0.124

-0.002, 0.251

0.053

Unknown

388

-0.82

1.21

-0.055

-0.194, 0.084

0.438

0.039

-0.089, 0.167

0.547

0.046

-0.082, 0.174

0.482

HbA1c at the start of treatment (NGSP, %)

Less than 7.20

473

-0.11

0.72

Reference

(< 0.001*)

Reference

(< 0.001*)

Reference

(< 0.001*)

7.20 - 7.84

696

-0.40

0.67

-0.283

-0.401, -0.165

< 0.001*

-0.391

-0.509, -0.273

< 0.001*

-0.380

-0.498, -0.262

< 0.001*

7.85 - 8.79

577

-0.65

0.87

-0.533

-0.655, -0.411

< 0.001*

-0.697

-0.822, -0.572

< 0.001*

-0.691

-0.816, -0.567

< 0.001*

8.80 or higher

593

-1.51

1.53

-1.395

-1.516, -1.273

< 0.001*

-1.582

-1.708, -1.455

< 0.001*

-1.583

-1.709, -1.458

< 0.001*

eGFR at the start of treatment (mL/min/1.73 m²)

Less than 63.56

441

-0.66

1.03

Reference

(< 0.001*)

Reference

(0.094)

63.56 - 77.51

441

-0.64

0.88

0.017

-0.132, 0.165

0.827

-0.035

-0.166, 0.097

0.607

77.52 - 91.43

440

-0.67

1.04

-0.013

-0.162, 0.135

0.861

0.027

-0.107, 0.161

0.694

91.44 or higher

443

-0.91

1.56

-0.258

-0.406, -0.109

< 0.001*

-0.047

-0.189, 0.094

0.513

Unknown

574

-0.57

1.02

0.086

-0.053, 0.226

0.226

0.107

-0.020, 0.235

0.099

**Table 4.** Factor Analysis of Changes in Body Weight After 12 Months
Explanatory variable	12-month change in body weight	Univariate model	Initial multivariate model (P < 0.05 in univariate model)	Final multivariate model (step-down method, P < 0.05)
*P < 0.05. Factors: study, sex, age (at registration), complications of diabetes (retinopathy, neuropathy, nephropathy), arteriosclerotic disease (cerebrovascular accident, myocardial infarction, angina, arteriosclerosis obliterans), smoking history, drinking history, duration of diabetes, body weight (at the start of treatment), BMI (at the start of treatment), HbA1c (at the start of treatment), and eGFR (at the start of treatment). SD: standard deviation; CI: confidence interval; BMI: body mass index; HbA1c: hemoglobin A1c; NGSP: National Glycohemoglobin Standardization Program.
Intercept	2,065	-0.01	3.54	-	-	-	0.623	0.181, 1.064	0.006*	0.640	0.201, 1.080	0.004*
Study
ASSET-K	980	0.11	2.94	Reference	-	(0.271)	Reference	-	(0.822)	Reference	-	(0.460)
ASSIST-K	832	-0.09	4.26	-0.208	-0.535, 0.119	0.212	-0.125	-0.519, 0.269	0.532	-0.209	-0.547, 0.129	0.226
ATTEST-K	253	-0.23	2.98	-0.339	-0.828, 0.150	0.174	-0.081	-0.620, 0.457	0.767	-0.161	-0.654, 0.332	0.522
Hypertension
No	827	0.35	3.16	Reference	-	(< 0.001*)	Reference	-	(0.030*)	Reference	-	(0.029*)
Yes	1,162	-0.30	3.80	-0.653	-0.967, -0.339	< 0.001*	-0.382	-0.703, -0.060	0.020*	-0.390	-0.710, -0.070	0.017*
Unknown	76	0.38	2.65	0.030	-0.799, 0.858	0.944	0.323	-0.661, 1.307	0.520	0.271	-0.614, 1.157	0.548
Fatty liver
No	1,466	0.11	2.91	Reference	-	(0.023*)	Reference	-	(0.713)
Yes	345	-0.46	5.47	-0.571	-0.985, -0.156	0.007*	-0.199	-0.686, 0.288	0.423
Unknown	254	-0.11	3.48	-0.225	-0.695, 0.246	0.349	-0.133	-0.724, 0.459	0.660
BMI at the start of treatment
Less than 22.0	491	0.68	2.52	Reference	-	(< 0.001*)	Reference	-	(< 0.001*)	Reference	-	(< 0.001*)
22.0 - 24.4	518	0.21	2.61	-0.466	-0.897, -0.034	0.034*	-0.435	-0.867, -0.002	0.049*	-0.443	-0.875, -0.011	0.044*
24.5 - 27.3	502	0.06	2.83	-0.620	-1.054, -0.185	0.005*	-0.569	-1.009, -0.128	0.011*	-0.586	-1.024, -0.147	0.009*
27.4 or higher	513	-0.94	5.24	-1.618	-2.050, -1.186	< 0.001*	-1.595	-2.048, -1.141	< 0.001*	-1.632	-2.076, -1.188	< 0.001*
Unknown	41	-0.29	3.00	-0.966	-2.079, 0.147	0.089	-1.051	-2.224, 0.122	0.079	-1.069	-2.236, 0.099	0.073
HbA1c at the start of treatment (NGSP, %)
Less than 7.30	489	-0.22	2.50	Reference	-	(< 0.001*)	Reference		(< 0.001*)	Reference	-	(< 0.001*)
7.30 - 7.89	520	0.13	2.88	0.353	-0.083, 0.788	0.112	0.412	-0.022, 0.846	0.063	0.417	-0.017, 0.851	0.060
7.90 - 8.79	517	-0.41	4.54	-0.188	-0.624, 0.248	0.398	-0.017	-0.460, 0.426	0.940	-0.019	-0.461, 0.424	0.935
8.80 or higher	539	0.42	3.76	0.635	0.204, 1.067	0.004*	0.933	0.488, 1.378	< 0.001*	0.923	0.479, 1.367	< 0.001*

Table 4. Factor Analysis of Changes in Body Weight After 12 Months

Explanatory variable

12-month change in body weight

Univariate model

Initial multivariate model (P < 0.05 in univariate model)

Final multivariate model (step-down method, P < 0.05)

Mean

Point estimate

95% CI

Category P value (variable P value)

Point estimate

95% CI

Category P value (variable P value)

Point estimate

95% CI

Category P value (variable P value)

*P < 0.05. Factors: study, sex, age (at registration), complications of diabetes (retinopathy, neuropathy, nephropathy), arteriosclerotic disease (cerebrovascular accident, myocardial infarction, angina, arteriosclerosis obliterans), smoking history, drinking history, duration of diabetes, body weight (at the start of treatment), BMI (at the start of treatment), HbA1c (at the start of treatment), and eGFR (at the start of treatment). SD: standard deviation; CI: confidence interval; BMI: body mass index; HbA1c: hemoglobin A1c; NGSP: National Glycohemoglobin Standardization Program.

Intercept

2,065

-0.01

3.54

0.623

0.181, 1.064

0.006*

0.640

0.201, 1.080

0.004*

Study

ASSET-K

980

0.11

2.94

Reference

(0.271)

Reference

(0.822)

Reference

(0.460)

ASSIST-K

832

-0.09

4.26

-0.208

-0.535, 0.119

0.212

-0.125

-0.519, 0.269

0.532

-0.209

-0.547, 0.129

0.226

ATTEST-K

253

-0.23

2.98

-0.339

-0.828, 0.150

0.174

-0.081

-0.620, 0.457

0.767

-0.161

-0.654, 0.332

0.522

Hypertension

827

0.35

3.16

Reference

(< 0.001*)

Reference

(0.030*)

Reference

(0.029*)

Yes

1,162

-0.30

3.80

-0.653

-0.967, -0.339

< 0.001*

-0.382

-0.703, -0.060

0.020*

-0.390

-0.710, -0.070

0.017*

Unknown

0.38

2.65

0.030

-0.799, 0.858

0.944

0.323

-0.661, 1.307

0.520

0.271

-0.614, 1.157

0.548

Fatty liver

1,466

0.11

2.91

Reference

(0.023*)

Reference

(0.713)

Yes

345

-0.46

5.47

-0.571

-0.985, -0.156

0.007*

-0.199

-0.686, 0.288

0.423

Unknown

254

-0.11

3.48

-0.225

-0.695, 0.246

0.349

-0.133

-0.724, 0.459

0.660

BMI at the start of treatment

Less than 22.0

491

0.68

2.52

Reference

(< 0.001*)

Reference

(< 0.001*)

Reference

(< 0.001*)

22.0 - 24.4

518

0.21

2.61

-0.466

-0.897, -0.034

0.034*

-0.435

-0.867, -0.002

0.049*

-0.443

-0.875, -0.011

0.044*

24.5 - 27.3

502

0.06

2.83

-0.620

-1.054, -0.185

0.005*

-0.569

-1.009, -0.128

0.011*

-0.586

-1.024, -0.147

0.009*

27.4 or higher

513

-0.94

5.24

-1.618

-2.050, -1.186

< 0.001*

-1.595

-2.048, -1.141

< 0.001*

-1.632

-2.076, -1.188

< 0.001*

Unknown

-0.29

3.00

-0.966

-2.079, 0.147

0.089

-1.051

-2.224, 0.122

0.079

-1.069

-2.236, 0.099

0.073

HbA1c at the start of treatment (NGSP, %)

Less than 7.30

489

-0.22

2.50

Reference

(< 0.001*)

Reference

(< 0.001*)

Reference

(< 0.001*)

7.30 - 7.89

520

0.13

2.88

0.353

-0.083, 0.788

0.112

0.412

-0.022, 0.846

0.063

0.417

-0.017, 0.851

0.060

7.90 - 8.79

517

-0.41

4.54

-0.188

-0.624, 0.248

0.398

-0.017

-0.460, 0.426

0.940

-0.019

-0.461, 0.424

0.935

8.80 or higher

539

0.42

3.76

0.635

0.204, 1.067

0.004*

0.933

0.488, 1.378

< 0.001*

0.923

0.479, 1.367

< 0.001*

**Table 5.** Factor Analysis of Changes in eGFR After 12 Months
Explanatory variable	12-month change in eGFR	Univariate model	Initial multivariate model (P < 0.05 in univariate model)	Final multivariate model (step-down method, P < 0.05)
*P < 0.05. Factors: study, sex, age (at registration), complications of diabetes (retinopathy, neuropathy, nephropathy), arteriosclerotic disease (cerebrovascular accident, myocardial infarction, angina, arteriosclerosis obliterans), smoking history, drinking history, duration of diabetes, body weight (at the start of treatment), BMI (at the start of treatment), HbA1c (at the start of treatment), and eGFR (at the start of treatment). eGFR: estimated glomerular filtration rate; SD: standard deviation; CI: confidence interval.
Intercept	1,418	-4.04	13.45	-	-	-	4.436	2.144, 6.728	< 0.001*	4.436	2.144, 6.728	< 0.001*
Study
ASSET-K	673	-3.88	14.94	Reference	-	(0.885)	Reference	-	(0.760)	Reference	-	(0.760)
ASSIST-K	426	-4.29	13.08	-0.413	-2.047, 1.222	0.621	-0.404	-2.009, 1.201	0.622	-0.404	-2.009, 1.201	0.622
ATTEST-K	319	-4.03	10.27	-0.152	-1.947, 1.643	0.868	0.291	-1.474, 2.056	0.746	0.291	-1.474, 2.056	0.746
Age (at registration)
57 or younger	335	-2.55	13.91	Reference	-	(0.064)	Reference	-	(< 0.001*)	Reference	-	(< 0.001*)
58 - 65	354	-4.34	13.78	-1.792	-3.800, 0.216	0.080	-4.279	-6.254, -2.305	< 0.001*	-4.279	-6.254, -2.305	< 0.001*
66 - 73	359	-3.90	10.75	-1.344	-3.345, 0.657	0.188	-5.059	-7.090, -3.028	< 0.001*	-5.059	-7.090, -3.028	< 0.001*
74 or older	370	-5.24	14.90	-2.685	-4.672, -0.698	0.008*	-7.530	-9.640, -5.420	< 0.001*	-7.530	-9.640, -5.420	< 0.001*
eGFR (at the start of treatment) (mL/min/1.73 m²)
Less than 63.00	338	-1.39	8.56	Reference	-	(< 0.001*)	Reference	-	(< 0.001*)	Reference	-	(< 0.001*)
63.00 - 77.16	339	-2.16	10.07	-0.767	-2.739, 1.206	0.446	-1.749	-3.717, 0.218	0.081	-1.749	-3.717, 0.218	0.081
77.17 - 91.54	338	-3.79	9.88	-2.402	-4.377, -0.428	0.017*	-3.983	-5.987, -1.980	< 0.001*	-3.983	-5.987, -1.980	< 0.001**
91.55 or higher	340	-9.47	17.38	-8.079	-10.051, -6.108	< 0.001*	-11.299	-13.441, -9.156	< 0.001*	-11.299	-13.441, -9.156	< 0.001*
Unknown	63	-0.37	27.71	1.021	-2.501, 4.543	0.570	-0.672	-4.284, 2.940	0.715	-0.672	-4.284, 2.940	0.715

Table 5. Factor Analysis of Changes in eGFR After 12 Months

Explanatory variable

12-month change in eGFR

Univariate model

Initial multivariate model (P < 0.05 in univariate model)

Final multivariate model (step-down method, P < 0.05)

Mean

Point estimate

95% CI

Category P value (variable P value)

Point estimate

95% CI

Category P value (variable P value)

Point estimate

95% CI

Category P value (variable P value)

*P < 0.05. Factors: study, sex, age (at registration), complications of diabetes (retinopathy, neuropathy, nephropathy), arteriosclerotic disease (cerebrovascular accident, myocardial infarction, angina, arteriosclerosis obliterans), smoking history, drinking history, duration of diabetes, body weight (at the start of treatment), BMI (at the start of treatment), HbA1c (at the start of treatment), and eGFR (at the start of treatment). eGFR: estimated glomerular filtration rate; SD: standard deviation; CI: confidence interval.

Intercept

1,418

-4.04

13.45

4.436

2.144, 6.728

< 0.001*

4.436

2.144, 6.728

< 0.001*

Study

ASSET-K

673

-3.88

14.94

Reference

(0.885)

Reference

(0.760)

Reference

(0.760)

ASSIST-K

426

-4.29

13.08

-0.413

-2.047, 1.222

0.621

-0.404

-2.009, 1.201

0.622

-0.404

-2.009, 1.201

0.622

ATTEST-K

319

-4.03

10.27

-0.152

-1.947, 1.643

0.868

0.291

-1.474, 2.056

0.746

0.291

-1.474, 2.056

0.746

Age (at registration)

57 or younger

335

-2.55

13.91

Reference

(0.064)

Reference

(< 0.001*)

Reference

(< 0.001*)

58 - 65

354

-4.34

13.78

-1.792

-3.800, 0.216

0.080

-4.279

-6.254, -2.305

< 0.001*

-4.279

-6.254, -2.305

< 0.001*

66 - 73

359

-3.90

10.75

-1.344

-3.345, 0.657

0.188

-5.059

-7.090, -3.028

< 0.001*

-5.059

-7.090, -3.028

< 0.001*

74 or older

370

-5.24

14.90

-2.685

-4.672, -0.698

0.008*

-7.530

-9.640, -5.420

< 0.001*

-7.530

-9.640, -5.420

< 0.001*

eGFR (at the start of treatment) (mL/min/1.73 m²)

Less than 63.00

338

-1.39

8.56

Reference

(< 0.001*)

Reference

(< 0.001*)

Reference

(< 0.001*)

63.00 - 77.16

339

-2.16

10.07

-0.767

-2.739, 1.206

0.446

-1.749

-3.717, 0.218

0.081

-1.749

-3.717, 0.218

0.081

77.17 - 91.54

338

-3.79

9.88

-2.402

-4.377, -0.428

0.017*

-3.983

-5.987, -1.980

< 0.001*

-3.983

-5.987, -1.980

< 0.001**

91.55 or higher

340

-9.47

17.38

-8.079

-10.051, -6.108

< 0.001*

-11.299

-13.441, -9.156

< 0.001*

-11.299

-13.441, -9.156

< 0.001*

Unknown

-0.37

27.71

1.021

-2.501, 4.543

0.570

-0.672

-4.284, 2.940

0.715

-0.672

-4.284, 2.940

0.715