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

Sponsor

University Hospital, Gentofte, Copenhagen (Other)

Overall Status

Completed

CT.gov ID

NCT03246451

Collaborator

University of Copenhagen (Other)

Enrollment

Location

Arms

5.3

Actual Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Glucose Metabolism Disorders	Drug: Placebo Oral Tablet Drug: Metformin Drug: Saline Drug: Exendin (9-39)	N/A

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Jul 1, 2017

Actual Primary Completion Date :

Dec 10, 2017

Actual Study Completion Date :

Dec 10, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo, oral tablet in 14 days and in liquid meal.	Drug: Placebo Oral Tablet 2-4 tablets in 14 days
Experimental: Metformin Metformin, oral tablet 2-4 x 500 mg in 14 days and in liquid meal.	Drug: Metformin 1000-2000 mg in 14 days
Experimental: Saline Saline infusion (9mg/mL) on experimental days	Drug: Saline 9 mg/ml saline infusion during experimental days
Experimental: Exendin(9-39) Exendin(9-39) infusion. GLP-1 receptor antagonist used as a study tool on experimental days.	Drug: Exendin (9-39) Infusion of GLP-1 receptor antagonist used as a tool during experimental days

Outcome Measures

Primary Outcome Measures

Plasma glucose [Minutes 240]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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