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Table 5 Exploratory comparison of glucose metabolism pharmacodynamic parameters between the volixibat 10 mg and placebo groups in patients with type 2 diabetes mellitus

From: Safety, tolerability and pharmacodynamics of apical sodium-dependent bile acid transporter inhibition with volixibat in healthy adults and patients with type 2 diabetes mellitus: a randomised placebo-controlled trial

 

Parameter

LS mean value

Difference in LS mean value (volixibat–placebo)

Volixibat

Placebo

Mean (90% CI)

P value

Glucose

 Day 14

Cpre (mmol/L)

8.9

10.7

–1.8 (−2.8, −0.9)

0.0064

Emax (mmol/L)

4.7

4.5

0.2 (−1.8, 2.2)

0.8524

AUC(0–3) (h.mmol/L)

34.3

39.2

−4.9 (−10.1, 0.3)

0.1173

rAUC(0–3) (h.mmol/L)

7.6

7.5

0.1 (−4.4, 4.6)

0.9739

 Day 28

Cpre (mmol/L)

9.2

10.7

−1.5 (−2.5, −0.6)

0.0163

Emax (mmol/L)

5.6

4.4

1.1 (−0.8, 3.1)

0.3147

AUC(0–3) (h.mmol/L)

37.8

39.6

−1.8 (−7.0, 3.4)

0.5408

rAUC(0–3) (h.mmol/L)

10.1

7.8

2.3 (−2.2, 6.8)

0.3714

Insulin

 Day 14

Cpre (mU/L)

10.0

9.6

0.4 (−3.3, 4.0)

0.8618

Emax (mU/L)

41.3

50.7

−9.4 (−26.9, 8.1)

0.3509

AUC(0–3) (h.mU/L)

94.2

92.7

1.4 (−24.1, 27.0)

0.9195

rAUC(0–3) (h.mU/L)

62.9

67.4

−4.5 (−29.8, 20.7)

0.7499

 Day 28

Cpre (mU/L)

9.6

9.9

−0.3 (−4.0, 3.4)

0.8832

Emax (mU/L)

42.9

39.5

3.5 (−14.0, 20.9)

0.7256

AUC(0–3) (h.mU/L)

91.8

82.4

9.4 (−16.2, 34.9)

0.5173

rAUC(0–3) (h.mU/L)

61.8

56.4

5.4 (−19.9, 30.6)

0.7045

C-peptide

 Day 14

Cpre (nmol/L)

0.780

0.823

−0.043 (−0.203, 0.117)

0.6313

Emax (nmol/L)

1.407

1.297

0.110 (−0.232, 0.452)

0.5706

AUC(0–3) (h.nmol/L)

5.002

4.985

0.017 (−0.719, 0.753)

0.9667

rAUC(0–3) (h.nmol/L)

2.631

2.601

0.030 (−0.826, 0.886)

0.9500

 Day 28

Cpre (nmol/L)

0.810

0.812

−0.002 (−0.162, 0.158)

0.9797

Emax (nmol/L)

1.407

1.164

0.243 (−0.099, 0.585)

0.2243

AUC(0–3) (h.nmol/L)

5.181

4.930

0.251 (−0.486, 0.987)

0.5443

rAUC(0–3) (h.nmol/L)

2.719

2.578

0.141 (−0.715, 0.996)

0.7700

GLP-1

 Day 14

Cpre (pM)

55

50

5 (−10, 20)

0.5552

Emax (pM)

23

29

−6 (−16, 4)

0.2731

AUC(0–3) (h.pM)

191

185

7 (−33, 47)

0.7643

rAUC(0–3) (h.pM)

26

35

−10 (−35, 16)

0.5128

 Day 28

Cpre (pM)

45

57

−12 (−27, 3)

0.1894

Emax (pM)

21

27

−6 (−16, 4)

0.2941

AUC(0–3) (h.pM)

161

200

−39 (−79, 1)

0.1100

rAUC(0–3) (h.pM)

25

29

−4 (−30, 21)

0.7645

GLP-2

 Day 14

Cpre (ngl/mL)

3.80

2.72

1.08 (−0.14, 2.31)

0.1396

Emax (ngl/mL)

1.16

2.15

−0.99 (−1.68, −0.30)

0.0280

AUC(0–3) (h.ngl/mL)

12.67

12.24

0.43 (−2.06, 2.92)

0.7597

rAUC(0–3) (h.ngl/mL)

1.46

3.59

−2.14 (−3.89, −0.38)

0.0524

 Day 28

Cpre (ngl/mL)

3.40

3.84

−0.44 (−1.66, 0.78)

0.5267

Emax (ngl/mL)

1.69

1.84

−0.15 (−0.84, 0.55)

0.7043

AUC(0–3) (h.ngl/mL)

12.77

14.30

−1.53 (−4.03, 0.96)

0.2886

rAUC(0–3) (h.ngl/mL)

2.77

2.30

0.47 (−1.28, 2.22)

0.6347

Peptide YY

 Day 14

Cpre (pg/mL)

770

668

102 (−173, 377)

0.5141

Emax (pg/mL)

227

270

−43 (−241, 155)

0.6986

AUC(0–3) (h.pg/mL)

2444

2448

−4 (−563, 555)

0.9897

rAUC(0–3) (h.pg/mL)

85

578

−493 (−942, −44)

0.0752

 Day 28

Cpre (pg/mL)

727

555

172 (−103, 447)

0.2808

Emax (pg/mL)

249

353

−105 (−302, 93)

0.3569

AUC(0–3) (h.pg/mL)

2398

2190

208 (−351, 767)

0.5122

rAUC(0–3) (h.pg/mL)

167

658

−491 (−941, −42)

0.0760

Glucose–insulin

 Day 14

HOMA2-%B (−)

37.4

26.2

11.2 (0.4, 22.0)

0.0888

HOMA2-IR (−)

1.5

1.5

0 (−0.6, 0.5)

0.9137

 Day 28

HOMA2-%B (−)

35.1

29.6

5.5 (−5.3, 16.3)

0.3724

HOMA2-IR (−)

1.4

1.5

−0.1 (−0.7, 0.4)

0.6466

  1. AUC (0–3) area under the effect (serum/plasma concentration)–time curve from time 0 to 3 h after the MTT calculated using the linear trapezoidal rule, CI confidence interval, C pre pre-MTT concentration, Emax maximum observed change from the pre-MTT baseline measurement, GLP glucagon-like peptide, HOMA2-IR updated homeostasis model assessment of insulin resistance, HOMA2-%B homeostasis model assessment of β-cell function, LS mean least-squares mean, MTT meal tolerance test, rAUC (0–3) area under the effect (serum/plasma concentration)–time curve from time 0 to 3 h after the MTT calculated using the linear trapezoidal rule with baseline subtracted (rAUC(0–3) = AUC(0–3) – [Cpre × 3]) (baseline is the value immediately prior to the standardised breakfast [Ensure Plus®, Abbott Nutrition, Lake Forest, IL, USA])
  2. Comparisons were made between parameters in the volixibat and placebo groups using a mixed model with treatment, study day and treatment-by-study-day interaction as fixed factors, participant within treatment as a random factor, and the day −1 baseline value for each participant as a covariate; data are from the pharmacodynamic analysis set
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BMC Gastroenterology

ISSN: 1471-230X

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