The Role of GLP-1 Receptor Signalling in the Glucose-lowering Effect of Metformin in Patients With T2D

University Hospital, Gentofte, Copenhagen

Status: Completed

Conditions: Glucose Metabolism Disorders

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

Study type: Interventional

Funder types: Other

Identifiers

NCT03246451

UHG-CFD-METEX

Details and patient eligibility

About

Delineation of the role of glucagon-like peptide-1 receptor signalling in the glucose-lowering effect of metformin during meal ingestion in patients with type 2 diabetes.

Full description

Aim: To evaluate the contribution of metformin-induced GLP-1 secretion on the glucose-lowering effect of metformin in patients with type 2 diabetes treated with metformin for 14 days. Furthermore, the investigators aim to elucidate the mechanisms by which metformin-induced GLP-1 secretion may affect glucose levels in patients with type 2 diabetes.

Fifteen patients with type 2 diabetes treated with lifestyle intervention and/or metformin as the only glucose-lowering drug will be enrolled in the study. The effect of a 14-day metformin treatment course on postprandial glucose tolerance will be examined with and without infusion of the GLP-1 receptor antagonist exendin9-39 in 15 patients with type 2 diabetes.

The double-blinded, placebo-controlled, randomised, cross-over study consists of four study days with concomitant infusions of A) placebo + placebo, B) placebo + exendin9-39, C) metformin + placebo and D) metformin + exendin9-39.

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)), with a HbA1c <58 mmol/mol.
• Caucasian ethnicity
• Lifestyle intervention and/or metformin monotherapy
• Normal haemoglobin
• Age >18 years
• BMI >23 kg/m2 and <35 kg/m2
• Informed and written consent

Exclusion criteria

• Liver disease
• Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery
• Hypo- or hyperphosphataemia
• Reduced kidney function or nephropathy
• Treatment with medicine that cannot be paused for 12 hours
• Intake of antibiotics two months prior to study
• Hypo- or hypercalcaemia
• 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

Placebo

Placebo Comparator group

Description:

Placebo, oral tablet in 14 days and in liquid meal.

Treatment:

Drug: Placebo Oral Tablet

Metformin

Experimental group

Description:

Metformin, oral tablet 2-4 x 500 mg in 14 days and in liquid meal.

Treatment:

Drug: Metformin

Saline

Experimental group

Description:

Saline infusion (9mg/mL) on experimental days

Treatment:

Drug: Saline

Exendin(9-39)

Experimental group

Description:

Exendin(9-39) infusion. GLP-1 receptor antagonist used as a study tool on experimental days.

Treatment:

Drug: Exendin (9-39)