Skip to main content

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