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

University Hospital, Gentofte, Copenhagen

Status: Completed

Conditions: Glucose Metabolism Disorders

Treatments: Drug: Placebo Oral Tablet; Drug: Acarbose; Drug: Placebo Saline; Drug: Exendin (9-39)

Study type: Interventional

Funder types: Other

Identifiers

NCT03241303

H-17007893

Details and patient eligibility

About

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

Full 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.

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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15 participants in 4 patient groups, including a placebo group

Acarbose

Experimental group

Description:

50 mg and 100 mg glucobay tablets. 2 weeks. Other name: Precose

Treatment:

Drug: Acarbose

Placebo Oral tablets

Placebo Comparator group

Description:

180 mg. 2 weeks.

Treatment:

Drug: Placebo Oral Tablet

Exendin (9-39)

Experimental group

Description:

Infusion of GLP-1 receptor antagonist as a study tool to block GLP-1 activity on experimental day.

Treatment:

Drug: Exendin (9-39)

Placbo Saline

Placebo Comparator group

Description:

9 mg/ml placebo saline infusion on experimental day.

Treatment:

Drug: Placebo Saline