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

Glucose Metabolism Disorders Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03246451
• Other study ID #: UHG-CFD-METEX
• Status: Completed
• Phase: N/A
• Start date: July 1, 2017
• Est. completion date: December 10, 2017

Study information

• Verified date: July 2018
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 10, 2017
• Est. primary completion date: December 10, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glucose Metabolism Disorders
• Metabolic Diseases

Intervention

Drug:
• Placebo Oral Tablet
2-4 tablets in 14 days
• Metformin
1000-2000 mg in 14 days
• Saline
9 mg/ml saline infusion during experimental days
• Exendin (9-39)
Infusion of GLP-1 receptor antagonist used as a tool during experimental days

Locations

Country	Name	City	State
Denmark	Center for Diabetes Research	Gentofte	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen	University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma glucose	The difference between the effect of metformin 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.	Minutes 240