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 5, May 2019, pages 311-320

Efficacy and Safety of Adding Sitagliptin in Type 2 Diabetes Patients on Insulin: Age-Stratified Comparison at One Year in the ASSIST-K Study

**Table 1.** Baseline Demographic Factors: All Patients on Insulin Receiving Add-on Sitagliptin Versus Patients With Sufficient HbA1c Data
	All patients on insulin	Patients with HbA1c data
Men: eGFR = 194 × serum creatinine^-1.094 × age at enrollment^-0.287; Women: eGFR = 194 × serum creatinine^-1.094 × age at enrollment^-0.287 × 0.739. Data are shown as the mean ± standard deviation unless otherwise noted. BMI: body mass index; eGFR; estimated glomerular filtration rate; HbA1c: hemoglobin A1c; NGSP: National Glycohemoglobin Standardization Program.
No. of patients	937 (100.0%)	821 (100.0%)
Sex
Male	508 (54.2%)	440 (53.6%)
Female	429 (45.8%)	381 (46.4%)
Age at enrollment	63.9 ± 12.3	64.2 ± 11.9
Diabetic complications
Retinopathy	315 (33.6%)	285 (34.7%)
Neuropathy	324 (34.6%)	296 (36.1%)
Nephropathy	367 (39.2%)	336 (40.9%)
Arteriosclerotic diseases
Cerebrovascular disease	72 (7.7%)	65 (7.9%)
Myocardial infarction/angina pectoris	162 (17.3%)	142 (17.3%)
Arteriosclerosis obliterans	87 (9.3%)	81 (9.9%)
Other complications
Hypertension	531 (56.7%)	478 (58.2%)
Dyslipidemia	588 (62.8%)	523 (63.7%)
Fatty liver	308 (32.9%)	272 (33.1%)
History of smoking	238 (25.4%)	207 (25.2%)
History of alcohol intake	231 (24.7%)	192 (23.4%)
Duration of diabetes (years)	17.0 ± 9.2	17.2 ± 9.1
Weight (baseline)	66.23 ± 15.51	66.15 ± 14.99
BMI (baseline)	25.38 ± 4.61	25.38 ± 4.48
HbA1c (baseline) (NGSP, %)	8.50 ± 1.35	8.49 ± 1.34
eGFR (baseline) (mL/min/1.73 m²)	75.851 ± 22.905	75.588 ± 22.502

Table 1. Baseline Demographic Factors: All Patients on Insulin Receiving Add-on Sitagliptin Versus Patients With Sufficient HbA1c Data

All patients on insulin

Patients with HbA1c data

Men: eGFR = 194 × serum creatinine^-1.094 × age at enrollment^-0.287; Women: eGFR = 194 × serum creatinine^-1.094 × age at enrollment^-0.287 × 0.739. Data are shown as the mean ± standard deviation unless otherwise noted. BMI: body mass index; eGFR; estimated glomerular filtration rate; HbA1c: hemoglobin A1c; NGSP: National Glycohemoglobin Standardization Program.

No. of patients

937 (100.0%)

821 (100.0%)

Sex

Male

508 (54.2%)

440 (53.6%)

Female

429 (45.8%)

381 (46.4%)

Age at enrollment

63.9 ± 12.3

64.2 ± 11.9

Diabetic complications

Retinopathy

315 (33.6%)

285 (34.7%)

Neuropathy

324 (34.6%)

296 (36.1%)

Nephropathy

367 (39.2%)

336 (40.9%)

Arteriosclerotic diseases

Cerebrovascular disease

72 (7.7%)

65 (7.9%)

Myocardial infarction/angina pectoris

162 (17.3%)

142 (17.3%)

Arteriosclerosis obliterans

87 (9.3%)

81 (9.9%)

Other complications

Hypertension

531 (56.7%)

478 (58.2%)

Dyslipidemia

588 (62.8%)

523 (63.7%)

Fatty liver

308 (32.9%)

272 (33.1%)

History of smoking

238 (25.4%)

207 (25.2%)

History of alcohol intake

231 (24.7%)

192 (23.4%)

Duration of diabetes (years)

17.0 ± 9.2

17.2 ± 9.1

Weight (baseline)

66.23 ± 15.51

66.15 ± 14.99

BMI (baseline)

25.38 ± 4.61

25.38 ± 4.48

HbA1c (baseline) (NGSP, %)

8.50 ± 1.35

8.49 ± 1.34

eGFR (baseline) (mL/min/1.73 m²)

75.851 ± 22.905

75.588 ± 22.502

**Table 2.** Demographic Factors of Each Age Group
	Age at enrollment	Intergroup comparison: P value
P < 0.050, P < 0.010, and **P < 0.001. Data are shown as the mean ± standard deviation unless otherwise noted. BMI: body mass index; eGFR; estimated glomerular filtration rate; HbA1c: hemoglobin A1c; NGSP: National Glycohemoglobin Standardization Program.
No. of patients analyzed	389 (100.0%)	267 (100.0%)	165 (100.0%)
Sex
Male	237 (60.9%)	126 (47.2%)	77 (46.7%)	Fisher’s exact test
Female	152 (39.1%)	141 (52.8%)	88 (53.3%)	< 0.001***	0.003**	0.921
Age at enrollment	54.0 ± 8.3	69.6 ± 2.9	79.2 ± 3.4	t-test
N	389	267	165	< 0.001***	< 0.001***	< 0.001***
Diabetic complications
Retinopathy
No	222 (57.1%)	131 (49.1%)	84 (50.9%)	Fisher’s exact test
Yes	124 (31.9%)	102 (38.2%)	59 (35.8%)	0.057	0.261	0.668
Neuropathy
No	223 (57.3%)	128 (47.9%)	68 (41.2%)	Fisher’s exact test
Yes	114 (29.3%)	108 (40.4%)	74 (44.8%)	0.004**	< 0.001***	0.244
Nephropathy
No	194 (49.9%)	124 (46.4%)	69 (41.8%)	Fisher’s exact test
Yes	146 (37.5%)	113 (42.3%)	77 (46.7%)	0.27	0.048*	0.346
Arteriosclerotic diseases
Cerebrovascular disease
No	311 (79.9%)	199 (74.5%)	121 (73.3%)	Fisher’s exact test
Yes	16 (4.1%)	32 (12.0%)	17 (10.3%)	< 0.001***	0.009**	0.752
Myocardial infarction
No	287 (73.8%)	176 (65.9%)	96 (58.2%)	Fisher’s exact test
Angina pectoris
Yes	40 (10.3%)	60 (22.5%)	42 (25.5%)	< 0.001***	< 0.001***	0.336
Arteriosclerosis
No	285 (73.3%)	199 (74.5%)	118 (71.5%)	Fisher’s exact test
Obliterans
Yes	33 (8.5%)	29 (10.9%)	19 (11.5%)	0.414	0.335	0.752
Other complications
Hypertension
No	157 (40.4%)	80 (30.0%)	35 (21.2%)	Fisher’s exact test
Yes	192 (49.4%)	167 (62.5%)	119 (72.1%)	0.002**	< 0.001***	0.041*
Dyslipidemia
No	106 (27.2%)	68 (25.5%)	57 (34.5%)	Fisher’s exact test
Yes	252 (64.8%)	178 (66.7%)	93 (56.4%)	0.648	0.076	0.035*
Fatty liver
No	152 (39.1%)	129 (48.3%)	83 (50.3%)	Fisher’s exact test
Yes	146 (37.5%)	82 (30.7%)	44 (26.7%)	0.024*	0.008**	0.486
History of smoking
No	167 (42.9%)	125 (46.8%)	84 (50.9%)	Fisher’s exact test
Yes	120 (30.8%)	59 (22.1%)	28 (17.0%)	0.041*	0.002**	0.237
History of alcohol intake
No	165 (42.4%)	113 (42.3%)	90 (54.5%)	Fisher’s exact test
Yes	114 (29.3%)	58 (21.7%)	20 (12.1%)	0.162	< 0.001***	0.004**
Duration of diabetes (years)	13.6 ± 7.2	19.8 ± 8.6	21.3 ± 10.5	t-test
N	331	227	141	< 0.001***	< 0.001***	0.123
Body weight (baseline)	72.06 ± 16.14	62.40 ± 11.30	58.23 ± 11.48	t-test
N	389	267	164	< 0.001***	< 0.001***	< 0.001*
BMI (baseline)	26.58 ± 4.81	24.55 ± 3.74	23.89 ± 4.03	t-test
N	376	256	159	< 0.001***	< 0.001***	0.089
HbA1c (baseline) (NGSP, %)	8.80 ± 1.50	8.24 ± 1.09	8.19 ± 1.13	t-test
N	389	267	165	< 0.001***	< 0.001***	0.644
eGFR (baseline) (mL/min/1.73 m²)	85.1 ± 21.7	70.0 ± 19.7	63.2 ± 18.8	t-test
N	285	176	140	< 0.001***	< 0.001***	0.002**

Table 2. Demographic Factors of Each Age Group

Age at enrollment

Intergroup comparison: P value

A) ≤ 64 years

B) 65 - 74 years

C) ≥ 75 years

A vs. B

A vs. C

B vs. C

*P < 0.050, **P < 0.010, and ***P < 0.001. Data are shown as the mean ± standard deviation unless otherwise noted. BMI: body mass index; eGFR; estimated glomerular filtration rate; HbA1c: hemoglobin A1c; NGSP: National Glycohemoglobin Standardization Program.

No. of patients analyzed

389 (100.0%)

267 (100.0%)

165 (100.0%)

Sex

Male

237 (60.9%)

126 (47.2%)

77 (46.7%)

Fisher’s exact test

Female

152 (39.1%)

141 (52.8%)

88 (53.3%)

< 0.001***

0.003**

0.921

Age at enrollment

54.0 ± 8.3

69.6 ± 2.9

79.2 ± 3.4

t-test

389

267

165

< 0.001***

Diabetic complications

Retinopathy

222 (57.1%)

131 (49.1%)

84 (50.9%)

Fisher’s exact test

Yes

124 (31.9%)

102 (38.2%)

59 (35.8%)

0.057

0.261

0.668

Neuropathy

223 (57.3%)

128 (47.9%)

68 (41.2%)

Fisher’s exact test

Yes

114 (29.3%)

108 (40.4%)

74 (44.8%)

0.004**

< 0.001***

0.244

Nephropathy

194 (49.9%)

124 (46.4%)

69 (41.8%)

Fisher’s exact test

Yes

146 (37.5%)

113 (42.3%)

77 (46.7%)

0.27

0.048*

0.346

Arteriosclerotic diseases

Cerebrovascular disease

311 (79.9%)

199 (74.5%)

121 (73.3%)

Fisher’s exact test

Yes

16 (4.1%)

32 (12.0%)

17 (10.3%)

< 0.001***

0.009**

0.752

Myocardial infarction

287 (73.8%)

176 (65.9%)

96 (58.2%)

Fisher’s exact test

Angina pectoris

Yes

40 (10.3%)

60 (22.5%)

42 (25.5%)

< 0.001***

0.336

Arteriosclerosis

285 (73.3%)

199 (74.5%)

118 (71.5%)

Fisher’s exact test

Obliterans

Yes

33 (8.5%)

29 (10.9%)

19 (11.5%)

0.414

0.335

0.752

Other complications

Hypertension

157 (40.4%)

80 (30.0%)

35 (21.2%)

Fisher’s exact test

Yes

192 (49.4%)

167 (62.5%)

119 (72.1%)

0.002**

< 0.001***

0.041*

Dyslipidemia

106 (27.2%)

68 (25.5%)

57 (34.5%)

Fisher’s exact test

Yes

252 (64.8%)

178 (66.7%)

93 (56.4%)

0.648

0.076

0.035*

Fatty liver

152 (39.1%)

129 (48.3%)

83 (50.3%)

Fisher’s exact test

Yes

146 (37.5%)

82 (30.7%)

44 (26.7%)

0.024*

0.008**

0.486

History of smoking

167 (42.9%)

125 (46.8%)

84 (50.9%)

Fisher’s exact test

Yes

120 (30.8%)

59 (22.1%)

28 (17.0%)

0.041*

0.002**

0.237

History of alcohol intake

165 (42.4%)

113 (42.3%)

90 (54.5%)

Fisher’s exact test

Yes

114 (29.3%)

58 (21.7%)

20 (12.1%)

0.162

< 0.001***

0.004**

Duration of diabetes (years)

13.6 ± 7.2

19.8 ± 8.6

21.3 ± 10.5

t-test

331

227

141

< 0.001***

0.123

Body weight (baseline)

72.06 ± 16.14

62.40 ± 11.30

58.23 ± 11.48

t-test

389

267

164

< 0.001***

< 0.001*

BMI (baseline)

26.58 ± 4.81

24.55 ± 3.74

23.89 ± 4.03

t-test

376

256

159

< 0.001***

0.089

HbA1c (baseline) (NGSP, %)

8.80 ± 1.50

8.24 ± 1.09

8.19 ± 1.13

t-test

389

267

165

< 0.001***

0.644

eGFR (baseline) (mL/min/1.73 m²)

85.1 ± 21.7

70.0 ± 19.7

63.2 ± 18.8

t-test

285

176

140

< 0.001***

0.002**

**Table 3.** Antidiabetic Agents
	Age at enrollment	Intergroup comparison: P value
P < 0.050, P < 0.010, and **P < 0.001. Data are shown as the mean ± standard deviation unless otherwise noted. NA: not applicable; OHA: oral hypoglycemic agent.
No. of patients analyzed	389 (100.0%)	267 (100.0%)	165 (100.0%)
Before sitagliptin therapy
Daily no. of insulin doses
0	0 (0.0%)	0 (0.0%)	0 (0.0%)	Wilcoxon test
1	71 (18.3%)	53 (19.9%)	39 (23.6%)	0.266	0.002**	0.031*
2	81 (20.8%)	55 (20.6%)	53 (32.1%)
3	103 (26.5%)	83 (31.1%)	33 (20.0%)
4	134 (34.4%)	76 (28.5%)	40 (24.2%)
Mean	2.8	2.7	2.4
OHAs				Fisher’s exact test
Sulfonylureas	76 (19.5%)	60 (22.5%)	34 (20.6%)	0.379	0.816	0.719
Biguanides	200 (51.4%)	98 (36.7%)	39 (23.6%)	< 0.001***	< 0.001***	0.006**
Thiazolidinediones	54 (13.9%)	24 (9.0%)	12 (7.3%)	0.065	0.031*	0.594
Alpha-glucosidase inhibitors	102 (26.2%)	71 (26.6%)	43 (26.1%)	0.928	1	1
Glinides	6 (1.5%)	4 (1.5%)	5 (3.0%)	1	0.317	0.312
Number of OHAs
0	122 (31.4%)	107 (40.1%)	69 (41.8%)	Wilcoxon test
1	138 (35.5%)	80 (30.0%)	66 (40.0%)	0.036*	< 0.001***	0.127
2	90 (23.1%)	65 (24.3%)	24 (14.5%)
3	39 (10.0%)	15 (5.6%)	6 (3.6%)
Mean	1.1	1	0.8
At the start of sitagliptin therapy
Sitagliptin dose	47.1 ± 9.7	45.1 ± 11.3	45.0 ± 10.0	Wilcoxon test
N	388	267	165	0.009**	0.027*	0.927
Daily no. of insulin doses
0	1 (0.3%)	1 (0.4%)	0 (0.0%)	Wilcoxon test
1	71 (18.3%)	56 (21.0%)	41 (24.8%)	0.19	0.003**	0.064
2	85 (21.9%)	56 (21.0%)	50 (30.3%)
3	100 (25.7%)	80 (30.0%)	35 (21.2%)
4	132 (33.9%)	74 (27.7%)	39 (23.6%)
Mean	2.7	2.6	2.4
OHAs				Fisher’s exact test
Sulfonylureas	74 (19.0%)	60 (22.5%)	31 (18.8%)	0.324	1	0.397
Biguanides	196 (50.4%)	94 (35.2%)	31 (18.8%)	< 0.001***	< 0.001***	< 0.001***
Thiazolidinediones	33 (8.5%)	13 (4.9%)	9 (5.5%)	0.087	0.292	0.824
Alpha-glucosidase inhibitors	74 (19.0%)	57 (21.3%)	30 (18.2%)	0.487	0.905	0.46
Glinides	1 (0.3%)	0 (0.0%)	0 (0.0%)	NA	NA	NA
No. of concomitant OHAs
0	137 (35.2%)	122 (45.7%)	90 (54.5%)	Wilcoxon test
1	145 (37.3%)	76 (28.5%)	54 (32.7%)	0.040*	< 0.001***	0.010*
2	88 (22.6%)	59 (22.1%)	17 (10.3%)
3	19 (4.9%)	10 (3.7%)	4 (2.4%)
Mean	1	0.8	0.6
After 12 months of sitagliptin therapy
Sitagliptin dose	52.8 ± 15.6	51.7 ± 17.2	50.3 ± 11.8	Wilcoxon test
N	384	264	162	0.148	0.121	0.898
Daily no. of insulin doses
0	7 (1.8%)	3 (1.1%)	3 (1.8%)	Wilcoxon test
1	70 (18.0%)	60 (22.5%)	43 (26.1%)	0.039*	0.007**	0.287
2	77 (19.8%)	55 (20.6%)	45 (27.3%)
3	102 (26.2%)	83 (31.1%)	28 (17.0%)
4	133 (34.2%)	66 (24.7%)	46 (27.9%)
Mean	2.7	2.6	2.4
OHAs				Fisher’s exact test
Sulfonylureas	66 (17.0%)	47 (17.6%)	36 (21.8%)	0.834	0.188	0.315
Biguanides	172 (44.2%)	74 (27.7%)	25 (15.2%)	< 0.001***	< 0.001***	0.003**
Thiazolidinediones	35 (9.0%)	15 (5.6%)	8 (4.8%)	0.134	0.118	0.828
Alpha-glucosidase inhibitors	75 (19.3%)	51 (19.1%)	34 (20.6%)	1	0.727	0.71
Glinides	0 (0.0%)	0 (0.0%)	0 (0.0%)	NA	NA	NA
Number of concomitant OHAs
0	160 (41.1%)	137 (51.3%)	90 (54.5%)	Wilcoxon test
1	125 (32.1%)	79 (29.6%)	51 (30.9%)	0.005**	< 0.001***	0.366
2	89 (22.9%)	45 (16.9%)	20 (12.1%)
3	15 (3.9%)	6 (2.2%)	4 (2.4%)
Mean	0.9	0.7	0.6

Table 3. Antidiabetic Agents

Age at enrollment

Intergroup comparison: P value

A) ≤ 64 years

B) 65 - 74 years

C) ≥ 75 years

A vs. B

A vs. C

B vs. C

*P < 0.050, **P < 0.010, and ***P < 0.001. Data are shown as the mean ± standard deviation unless otherwise noted. NA: not applicable; OHA: oral hypoglycemic agent.

No. of patients analyzed

389 (100.0%)

267 (100.0%)

165 (100.0%)

Before sitagliptin therapy

Daily no. of insulin doses

0 (0.0%)

Wilcoxon test

71 (18.3%)

53 (19.9%)

39 (23.6%)

0.266

0.002**

0.031*

81 (20.8%)

55 (20.6%)

53 (32.1%)

103 (26.5%)

83 (31.1%)

33 (20.0%)

134 (34.4%)

76 (28.5%)

40 (24.2%)

Mean

2.8

2.7

2.4

OHAs

Fisher’s exact test

Sulfonylureas

76 (19.5%)

60 (22.5%)

34 (20.6%)

0.379

0.816

0.719

Biguanides

200 (51.4%)

98 (36.7%)

39 (23.6%)

< 0.001***

0.006**

Thiazolidinediones

54 (13.9%)

24 (9.0%)

12 (7.3%)

0.065

0.031*

0.594

Alpha-glucosidase inhibitors

102 (26.2%)

71 (26.6%)

43 (26.1%)

0.928

Glinides

6 (1.5%)

4 (1.5%)

5 (3.0%)

0.317

0.312

Number of OHAs

122 (31.4%)

107 (40.1%)

69 (41.8%)

Wilcoxon test

138 (35.5%)

80 (30.0%)

66 (40.0%)

0.036*

< 0.001***

0.127

90 (23.1%)

65 (24.3%)

24 (14.5%)

39 (10.0%)

15 (5.6%)

6 (3.6%)

Mean

1.1

0.8

At the start of sitagliptin therapy

Sitagliptin dose

47.1 ± 9.7

45.1 ± 11.3

45.0 ± 10.0

Wilcoxon test

388

267

165

0.009**

0.027*

0.927

Daily no. of insulin doses

1 (0.3%)

1 (0.4%)

0 (0.0%)

Wilcoxon test

71 (18.3%)

56 (21.0%)

41 (24.8%)

0.19

0.003**

0.064

85 (21.9%)

56 (21.0%)

50 (30.3%)

100 (25.7%)

80 (30.0%)

35 (21.2%)

132 (33.9%)

74 (27.7%)

39 (23.6%)

Mean

2.7

2.6

2.4

OHAs

Fisher’s exact test

Sulfonylureas

74 (19.0%)

60 (22.5%)

31 (18.8%)

0.324

0.397

Biguanides

196 (50.4%)

94 (35.2%)

31 (18.8%)

< 0.001***

Thiazolidinediones

33 (8.5%)

13 (4.9%)

9 (5.5%)

0.087

0.292

0.824

Alpha-glucosidase inhibitors

74 (19.0%)

57 (21.3%)

30 (18.2%)

0.487

0.905

0.46

Glinides

1 (0.3%)

0 (0.0%)

No. of concomitant OHAs

137 (35.2%)

122 (45.7%)

90 (54.5%)

Wilcoxon test

145 (37.3%)

76 (28.5%)

54 (32.7%)

0.040*

< 0.001***

0.010*

88 (22.6%)

59 (22.1%)

17 (10.3%)

19 (4.9%)

10 (3.7%)

4 (2.4%)

Mean

0.8

0.6

After 12 months of sitagliptin therapy

Sitagliptin dose

52.8 ± 15.6

51.7 ± 17.2

50.3 ± 11.8

Wilcoxon test

384

264

162

0.148

0.121

0.898

Daily no. of insulin doses

7 (1.8%)

3 (1.1%)

3 (1.8%)

Wilcoxon test

70 (18.0%)

60 (22.5%)

43 (26.1%)

0.039*

0.007**

0.287

77 (19.8%)

55 (20.6%)

45 (27.3%)

102 (26.2%)

83 (31.1%)

28 (17.0%)

133 (34.2%)

66 (24.7%)

46 (27.9%)

Mean

2.7

2.6

2.4

OHAs

Fisher’s exact test

Sulfonylureas

66 (17.0%)

47 (17.6%)

36 (21.8%)

0.834

0.188

0.315

Biguanides

172 (44.2%)

74 (27.7%)

25 (15.2%)

< 0.001***

0.003**

Thiazolidinediones

35 (9.0%)

15 (5.6%)

8 (4.8%)

0.134

0.118

0.828

Alpha-glucosidase inhibitors

75 (19.3%)

51 (19.1%)

34 (20.6%)

0.727

0.71

Glinides

0 (0.0%)

Number of concomitant OHAs

160 (41.1%)

137 (51.3%)

90 (54.5%)

Wilcoxon test

125 (32.1%)

79 (29.6%)

51 (30.9%)

0.005**

< 0.001***

0.366

89 (22.9%)

45 (16.9%)

20 (12.1%)

15 (3.9%)

6 (2.2%)

4 (2.4%)

Mean

0.9

0.7

0.6

**Table 4.** Adverse Events
	All patients	Age at enrollment	Intergroup comparison: P value
No. of patients analyzed	821 (100.0%)	389 (100.0%)	267 (100.0%)	165 (100.0%)	Fisher’s exact test
Severe hypoglycemia	24 (2.9%)	12 (3.1%)	8 (3.0%)	4 (2.4%)	1.000	0.787	1.000
Gastrointestinal symptoms	9 (1.1%)	5 (1.3%)	3 (1.1%)	1 (0.6%)	1.000	0.675	1.000
Constipation	20 (2.4%)	9 (2.3%)	4 (1.5%)	7 (4.2%)	0.575	0.266	0.114
Others	20 (2.4%)	5 (1.3%)	9 (3.4%)	6 (3.6%)	0.097	0.093	1.000

Table 4. Adverse Events

All patients

Age at enrollment

Intergroup comparison: P value

A) ≤ 64 years

B) 65 - 74 years

C) ≥ 75 years

A vs. B

A vs. C

B vs. C

No. of patients analyzed

821 (100.0%)

389 (100.0%)

267 (100.0%)

165 (100.0%)

Fisher’s exact test

Severe hypoglycemia

24 (2.9%)

12 (3.1%)

8 (3.0%)

4 (2.4%)

1.000

0.787

1.000

Gastrointestinal symptoms

9 (1.1%)

5 (1.3%)

3 (1.1%)

1 (0.6%)

1.000

0.675

1.000

Constipation

20 (2.4%)

9 (2.3%)

4 (1.5%)

7 (4.2%)

0.575

0.266

0.114

Others

20 (2.4%)

5 (1.3%)

9 (3.4%)

6 (3.6%)

0.097

0.093

1.000