GLP-1-mediated Gluco-metabolic Effects of Bile Acid Sequestration
Status:
Completed
Trial end date:
2021-09-01
Target enrollment:
Participant gender:
Summary
The objective of this study is to investigate the potential GLP-1-mediated contribution to
the well-established glucose-lowering effect of sevelamer-induced bile acid sequestration .
Exendin9-39 has been demonstrated to act as a potent and specific GLP-1 receptor antagonist
with no partial agonistic potential and is considered a useful tool in the assessment of
GLP-1 physiology. The aim is to evaluate any contribution of sevelamer-induced GLP-1
secretion to the reduced plasma glucose concentrations observed after treatment with
sevelamer. A randomised placebo-controlled cross-over study involving two 17-day treatment
periods with sevelamer and placebo, respectively, in metformin-treated patients with type 2
diabetes, will be conducted. The impact of bile acid sequestration on GLP-1 secretion and
effect will be examined during two randomised experimental days after 15 and 17 days of
treatment with sevelamer (1,600 mg three times a day) and placebo, respectively. During each
of these two experimental days, a meal test with concomitant exendin9-39 infusion or placebo
will be performed (for evaluation of any GLP-1-mediated effects). Postprandial plasma glucose
excursion is the primary endpoint, and secondary endpoints include postprandial plasma/serum
excursions of insulin, C-peptide, GLP-1, glucagon, glucose-dependent insulinotropic
polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY (PYY), oxyntomodulin, ghrelin,
fibroblast growth factor (FGF)-19, FGF-21, C4 (an intermediate in the de novo synthesis of
bile acids), cholecystokinin (CCK), bile acids and plasma lipids. Furthermore, gastric
emptying, gallbladder emptying, liver fat content, appetite and ad libitum food intake will
be examined.
Phase:
N/A
Details
Lead Sponsor:
Steno Diabetes Center Steno Diabetes Center Copenhagen