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Table 5 Relationship between treatment duration and laboratory parameters

From: Comparative effect of dipeptidyl-peptidase 4 inhibitors on laboratory parameters in patients with diabetes mellitus

Laboratory parameters

Drugs

Time point

N

Unadjusted

p-value

aAdjusted

p-value

LS Mean (95%CI)

LS Mean (95%CI)

HbA1c (%)

Sitagliptin

   

<.0001

 

<.0001

baseline

879

7.8 (7.7, 7.9)

reference

7.8 (7.8, 7.9)

reference

0-3 M

835

7.4 (7.3, 7.4)

*

7.4 (7.3, 7.5)

*

3-12 M

208

7.2 (7, 7.3)

*

7.2 (7.1, 7.3)

*

Vildagliptin

   

<.0001

 

<.0001

baseline

253

7.8 (7.6, 7.9)

reference

7.7 (7.6, 7.9)

reference

0-3 M

241

7.2 (7, 7.3)

*

7.1 (7, 7.3)

*

3-12 M

64

7.1 (6.9, 7.3)

*

7 (6.8, 7.2)

*

Teneligliptin

   

<.0001

 

<.0001

baseline

260

7.8 (7.7, 8)

reference

7.9 (7.7, 8)

reference

0-3 M

237

7.2 (7.1, 7.4)

*

7.2 (7.1, 7.4)

*

3-12 M

95

6.9 (6.7, 7.1)

*

6.9 (6.7, 7.1)

*

Alogliptin

   

<.0001

 

<.0001

baseline

237

7.4 (7.3, 7.5)

reference

7.4 (7.3, 7.6)

reference

0-3 M

216

7 (6.8, 7.1)

*

7 (6.9, 7.1)

*

3-12 M

61

6.8 (6.6, 7)

*

6.8 (6.6, 7)

*

Linagliptin

   

<.0001

 

<.0001

baseline

180

7.4 (7.3, 7.6)

reference

7.4 (7.3, 7.6)

reference

0-3 M

176

7 (6.8, 7.1)

*

6.9 (6.8, 7.1)

*

3-12 M

58

6.8 (6.6, 7)

*

6.8 (6.6, 7)

*

creatinine (mg/dL)

Sitagliptin

   

<.0001

 

<.0001

baseline

831

0.8 (0.78, 0.82)

reference

0.76 (0.75, 0.78)

reference

0-3 M

795

0.82 (0.8, 0.84)

*

0.79 (0.77, 0.8)

*

3-12 M

198

0.86 (0.83, 0.88)

*

0.82 (0.8, 0.85)

*

Vildagliptin

   

0.035

 

0.0375

baseline

233

0.89 (0.84, 0.94)

reference

0.84 (0.79, 0.89)

reference

0-3 M

222

0.91 (0.86, 0.97)

 

0.87 (0.81, 0.92)

 

3-12 M

60

0.93 (0.87, 0.99)

 

0.88 (0.82, 0.94)

 

Teneligliptin

   

<.0001

 

<.0001

baseline

259

0.94 (0.88, 1)

reference

0.88 (0.82, 0.94)

reference

0-3 M

239

0.98 (0.91, 1.04)

*

0.92 (0.86, 0.98)

*

3-12 M

98

1.05 (0.98, 1.12)

*

0.99 (0.92, 1.06)

*

Alogliptin

   

0.0001

 

0.0001

baseline

226

0.82 (0.79, 0.86)

reference

0.77 (0.74, 0.8)

reference

0-3 M

205

0.85 (0.82, 0.88)

*

0.8 (0.77, 0.83)

*

3-12 M

62

0.86 (0.82, 0.9)

*

0.81 (0.77, 0.85)

*

Linagliptin

   

0.002

 

0.0021

baseline

174

1.04 (0.95, 1.12)

reference

0.99 (0.91, 1.08)

reference

0-3 M

169

1.08 (1, 1.16)

*

1.03 (0.95, 1.12)

*

3-12 M

58

1.12 (1.03, 1.21)

*

1.07 (0.98, 1.17)

*

eGFR (mL/min/1.73m2)

Sitagliptin

   

<.0001

 

<.0001

baseline

831

74 (72.7, 75.4)

reference

74.4 (73.2, 75.5)

reference

0-3 M

795

72.1 (70.8, 73.5)

*

72.4 (71.3, 73.6)

*

3-12 M

198

70 (68.3, 71.7)

*

70.4 (68.8, 71.9)

*

Vildagliptin

   

<.0001

 

<.0001

baseline

233

70.3 (67.3, 73.3)

reference

70.6 (67.7, 73.6)

reference

0-3 M

222

67.5 (64.5, 70.6)

*

67.8 (64.9, 70.8)

*

3-12 M

60

69 (65.6, 72.4)

 

69.3 (66, 72.7)

 

Teneligliptin

   

<.0001

 

<.0001

baseline

259

66.3 (63.6, 69)

reference

67 (64.4, 69.5)

reference

0-3 M

239

63.6 (60.8, 66.3)

*

64.2 (61.7, 66.8)

*

3-12 M

98

63 (60, 66)

*

63.7 (60.8, 66.5)

*

Alogliptin

   

0.0009

 

0.0009

baseline

226

72.5 (70, 75)

reference

73.2 (70.8, 75.7)

reference

0-3 M

205

70.6 (68, 73.1)

*

71.3 (68.8, 73.8)

*

3-12 M

62

70.4 (67.5, 73.3)

 

71.2 (68.3, 74.1)

 

Linagliptin

   

0.001

 

0.001

baseline

174

61.8 (58, 65.7)

reference

62.2 (58.3, 66.1)

reference

0-3 M

169

59.8 (56, 63.7)

*

60.2 (56.3, 64.1)

*

3-12 M

58

59.5 (55.4, 63.6)

*

59.9 (55.7, 64)

*

HDL (mg/dL)

Sitagliptin

   

0.0037

 

0.0033

baseline

726

51.3 (50.3, 52.3)

reference

52.2 (51.2, 53.2)

reference

0-3 M

685

50.5 (49.4, 51.5)

*

51.4 (50.3, 52.4)

*

3-12 M

141

50 (48.6, 51.5)

 

50.9 (49.5, 52.3)

*

Vildagliptin

   

0.0007

 

0.0008

baseline

203

47.3 (45.6, 49)

reference

48.6 (46.9, 50.3)

reference

0-3 M

194

46.1 (44.4, 47.8)

*

47.4 (45.7, 49.1)

*

3-12 M

50

44.5 (42.3, 46.6)

*

45.8 (43.7, 48)

*

Teneligliptin

   

0.427

 

0.4293

baseline

212

50.1 (48.3, 52)

reference

51.8 (49.9, 53.6)

reference

0-3 M

188

50.2 (48.4, 52.1)

 

51.8 (50, 53.7)

 

3-12 M

78

49.3 (47.1, 51.4)

 

50.9 (48.7, 53)

 

Alogliptin

   

0.5739

 

0.5798

baseline

183

47.5 (45.6, 49.5)

reference

48.6 (46.5, 50.7)

reference

0-3 M

163

47.1 (45.1, 49)

 

48.1 (46, 50.2)

 

3-12 M

47

46.7 (44.2, 49.3)

 

47.8 (45.1, 50.4)

 

Linagliptin

   

0.3891

 

0.3894

baseline

144

48.9 (46.8, 51)

reference

49.7 (47.5, 51.9)

reference

0-3 M

140

48.3 (46.2, 50.4)

 

49.1 (46.9, 51.3)

 

3-12 M

43

49.7 (47, 52.3)

 

50.4 (47.7, 53.2)

 

TC (mg/dL)

Sitagliptin

   

0.0004

 

0.0004

baseline

728

192.3 (189.8, 194.8)

reference

194 (191.5, 196.5)

reference

0-3 M

682

188.9 (186.3, 191.4)

*

190.6 (188, 193.2)

*

3-12 M

161

194.3 (190.4, 198.3)

 

196 (192.1, 200)

 

Vildagliptin

   

0.0071

 

0.0024

baseline

204

188.7 (183.6, 193.8)

reference

190.9 (185.6, 196.2)

reference

0-3 M

194

183.4 (178.2, 188.6)

*

185.5 (180.2, 190.9)

*

3-12 M

50

183.7 (176.5, 190.9)

 

186 (178.7, 193.4)

 

Teneligliptin

   

0.0668

 

0.0764

baseline

217

190.1 (185.2, 195)

reference

193.6 (188.7, 198.5)

reference

0-3 M

196

186.5 (181.5, 191.5)

 

189.9 (184.9, 194.9)

 

3-12 M

76

185 (178.5, 191.4)

 

188.9 (182.4, 195.3)

 

Alogliptin

   

0.043*

 

0.0372

baseline

176

188 (182.5, 193.5)

reference

189.5 (183.6, 195.4)

reference

0-3 M

153

183.4 (177.8, 189)

*

184.8 (178.8, 190.8)

*

3-12 M

48

188.4 (180.9, 195.9)

 

190.1 (182.3, 197.9)

 

Linagliptin

   

0.1222

 

0.1105

baseline

151

189.3 (183.1, 195.5)

reference

191.6 (185.2, 198)

 

0-3 M

146

186.3 (180.1, 192.5)

 

188.6 (182.2, 195)

 

3-12 M

50

191.4 (183.8, 198.9)

 

193.8 (186.1, 201.6)

 

TG (mg/dL)

Sitagliptin

   

0.0473

 

0.0469

baseline

755

145.1 (139.4, 150.7)

reference

142.9 (137.1, 148.8)

reference

0-3 M

712

139.1 (133.3, 144.8)

*

136.9 (131, 142.8)

*

3-12 M

160

141.9 (132.4, 151.4)

 

140 (130.4, 149.6)

 

Vildagliptin

   

0.0203

 

0.0072

baseline

206

160.3 (148.9, 171.7)

reference

190.9 (185.6, 196.2)

reference

0-3 M

195

148.2 (136.6, 159.7)

*

185.5 (180.2, 190.9)

*

3-12 M

54

144.4 (126.8, 162)

 

186 (178.7, 193.4)

 

Teneligliptin

   

0.1054

 

0.1204

baseline

233

151.3 (140.7, 161.9)

reference

149.4 (138.6, 160.3)

reference

0-3 M

209

145.2 (134.2, 156.1)

 

143.1 (132, 154.3)

 

3-12 M

85

136.4 (121.3, 151.4)

 

135.2 (120, 150.4)

 

Alogliptin

   

0.0086

 

0.0077

baseline

197

155 (143.6, 166.3)

reference

155.3 (143.1, 167.5)

reference

0-3 M

174

140.3 (128.6, 152)

*

140.5 (128, 153)

*

3-12 M

51

152.2 (135, 169.5)

 

153 (135.1, 170.9)

 

Linagliptin

   

0.9511

 

0.9521

baseline

159

146.2 (134, 158.5)

reference

146.8 (134, 159.6)

reference

0-3 M

154

144.5 (132.2, 156.9)

 

145.1 (132.1, 158)

 

3-12 M

49

144.6 (126.1, 163)

 

145.4 (126.5, 164.4)

 

AST (U/L)

Sitagliptin

   

0.0879

 

0.0856

baseline

830

27.8 (26.6, 29)

reference

27.5 (26.3, 28.7)

reference

0-3 M

794

26.8 (25.6, 28.1)

 

26.5 (25.3, 27.8)

 

3-12 M

199

28 (26.2, 29.8)

 

27.7 (25.9, 29.5)

 

Vildagliptin

   

0.3947

 

0.3942

baseline

232

30.3 (27.1, 33.5)

reference

30.5 (27.1, 33.9)

reference

0-3 M

222

31.2 (28, 34.4)

 

31.4 (28, 34.8)

 

3-12 M

57

32.6 (28.2, 37)

 

32.8 (28.2, 37.4)

 

Teneligliptin

   

0.7444

 

0.7366

baseline

256

29.8 (26.9, 32.8)

reference

30.6 (27.5, 33.6)

reference

0-3 M

236

28.5 (25.5, 31.6)

 

29.2 (26.1, 32.4)

 

3-12 M

97

29.4 (24.9, 33.9)

 

30.2 (25.7, 34.8)

 

Alogliptin

   

0.0056

 

0.0056

baseline

221

29.9 (27.3, 32.4)

reference

29.5 (26.7, 32.3)

Reference

0-3 M

200

26.8 (24.2, 29.4)

*

26.4 (23.6, 29.2)

*

3-12 M

61

28.4 (24.8, 32)

 

28 (24.3, 31.8)

 

Linagliptin

   

0.3101

 

0.3365

baseline

176

24.7 (22.7, 26.7)

reference

25.1 (23.1, 27.1)

reference

0-3 M

171

24.2 (22.2, 26.2)

 

24.6 (22.6, 26.7)

 

3-12 M

58

23.3 (20.9, 25.7)

 

23.8 (21.3, 26.3)

 

ALT (U/L)

Sitagliptin

   

<.0001

 

<.0001

baseline

830

30.4 (28.8, 32)

reference

29.8 (28.3, 31.4)

reference

0-3 M

794

28.1 (26.5, 29.7)

*

27.5 (25.9, 29.1)

*

3-12 M

199

27.8 (25.5, 30.1)

*

27.2 (25, 29.5)

*

Vildagliptin

   

0.1288

 

0.1286

baseline

233

32.3 (29.1, 35.6)

reference

32 (28.7, 35.2)

reference

0-3 M

223

30.2 (27, 33.5)

 

29.8 (26.5, 33.2)

 

3-12 M

58

31.6 (27.2, 36)

 

31.1 (26.7, 35.6)

 

Teneligliptin

   

0.0824

 

0.089

baseline

256

30.2 (27, 33.4)

reference

30.6 (27.3, 33.9)

reference

0-3 M

236

27.5 (24.2, 30.8)

 

27.9 (24.5, 31.3)

 

3-12 M

97

25.5 (20.9, 30.2)

 

26 (21.3, 30.8)

 

Alogliptin

   

<.0001

 

<.0001

baseline

223

34.7 (31.1, 38.3)

reference

34.1 (30.3, 37.9)

reference

0-3 M

202

29 (25.4, 32.6)

*

28.4 (24.5, 32.2)

*

3-12 M

61

29.6 (24.8, 34.5)

*

29.1 (24, 34.1)

*

Linagliptin

   

<.0001

 

<.0001

baseline

176

26.2 (22.6, 29.8)

reference

26.5 (23.2, 29.9)

reference

0-3 M

171

23.4 (19.8, 26.9)

*

23.7 (20.3, 27.1)

*

3-12 M

58

22.4 (18.4, 26.3)

*

22.8 (19, 26.6)

*

  1. *p < 0.05 (compared with baseline period, multiple-comparison test: Dunnett’s post-hoc analysis), aAdjusted for age and sex
  2. LS mean least square mean, CI confidence interval, HbA1c hemoglobin A1c, eGFR estimated glomerular filtration rate, HDL high density lipoprotein, TC total cholesterol, TG triglyceride, AST aspartate aminotransferase, ALT alanine aminotransferase
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