GLP-1-mediated Gluco-metabolic Effects of Bile Acid Sequestration (SeveX)

Steno Diabetes Centers

Status

Completed

Conditions

Type 2 Diabetes Mellitus

Treatments

Drug: Sevelamer

Drug: Placebo

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT03739268

SeveX2018

Details and patient eligibility

About

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.

Enrollment

17 patients

Sex

All

Ages

40 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Type 2 diabetes for at least 3 months (diagnosed according to the criteria of the World Health Organization (WHO))
Men and postmenopausal women
Metformin applied as the only glucose-lowering drug
Caucasian ethnicity
Normal haemoglobin
Age above 40 years and below 75 years
BMI >23 kg/m2 and <35 kg/m2
Informed and written consent

Exclusion criteria

Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary disorder
Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery
Nephropathy (serum creatinine >150 µM and/or albuminuria)
Hypo- or hyperthyroidism
Hypo- or hypercalcaemia
Hypo- or hyperphosphataemia
Active or recent malignant disease
Treatment with medicine that cannot be paused for 12 hours
Treatment with oral anticoagulants
Any treatment or condition requiring acute or sub-acute medical or surgical intervention
Any condition considered incompatible with participation by the investigators