Delineation of the Role of Glucagon-like Peptide-1 Signalling in Relation to Increased Carbohydrate Content in the Distal Small Intestines

Not Applicable

Completed

• Conditions: Glucose Metabolism Disorders
• Interventions: Drug: Placebo Oral Tablet; Drug: Acarbose; Drug: Placebo Saline; Drug: Exendin (9-39)

• Registration Number: NCT03241303
• Lead Sponsor: University Hospital, Gentofte, Copenhagen

Brief Summary

Investigation of GLP-1 signalling in the glucose-lowering effect of increased carbohydrate content in the distal small intestines induced by alpha-glucosidase inhibition during meal ingestion in patients with type 2 diabetes

Detailed Description

The primary aim of the study is to investigate whether GLP-1 released as a result of increased carbohydrate content in the distal and L cell-rich part of the small intestine after a meal affects postprandial plasma glucose levels in patients with type 2 diabetes. This will be done by applying an alpha-glucosidase inhibitor (to increase the postprandial carbohydrate content in the distal small intestine) and the specific GLP-1 receptor antagonist exendin(9-39) (to isolate any GLP-1-mediated effects) during meal tests in patients with type 2 diabetes.

Study Timeline

• Study Start: 2017-08-01
• Study First Submitted: 2017-08-02
• Study First Submitted QC: 2017-08-04
• Study First Posted: 2017-08-07
• Primary Completion: 2018-01-01
• Study Completion: 2018-01-01
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-25
• Last Update Posted: 2020-03-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Type 2 diabetes for at least three months (diagnosed according to the criteria of the World Health Organization (WHO)) treated with metformin monotherapy
• Caucasian ethnicity
• Normal haemoglobin
• Age >18 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
• Reduced kidney function or nephropathy (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (based on serum creatinine) and/or albuminuria
• Treatment with medicine that cannot be paused for 12 hours
• Intake of antibiotics two months prior to study
• Treatment with glucose-lowering drugs other than metformin
• Hypo- and hyperthyroidism
• Treatment with oral anticoagulants
• Active or recent malignant disease
• Any treatment or condition requiring acute or sub-acute medical or surgical intervention
• Lack of effective birth control in premenopausal women
• Positive pregnancy test on study days in premenopausal women
• Pregnancy
• Women who are breastfeeding
• Any condition considered incompatible with participation by the investigators
• If the subjects receive any antibiotic treatment while included in the study they will be excluded

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo Oral tablets	Placebo Oral Tablet	180 mg. 2 weeks.
Acarbose	Acarbose	50 mg and 100 mg glucobay tablets. 2 weeks. Other name: Precose
Placbo Saline	Placebo Saline	9 mg/ml placebo saline infusion on experimental day.
Exendin (9-39)	Exendin (9-39)	Infusion of GLP-1 receptor antagonist as a study tool to block GLP-1 activity on experimental day.

Primary Outcome Measures

Name	Time	Method
Plasma glucose	240 min	The primary outcome is the difference between the effect of increased carbohydrate content in the distal part of the small intestine (obtained by inhibiting alpha-glucosidase with acarbose) on postprandial glucose tolerance (as assessed by area under curve (AUC) for plasma glucose during a standardised liquid mixed meal test) with and without blockade of GLP-1 signalling by exendin(9-39).

Trial Locations

Locations (1)

Center for Diabetesresearch; 🇩🇰 Hellerup, Denmark