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

Not Applicable

Completed

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

• Registration Number: NCT03246451
• Lead Sponsor: University Hospital, Gentofte, Copenhagen

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.

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 Timeline

• Study Start: 2017-07-01
• Study First Submitted: 2017-08-01
• Study First Submitted QC: 2017-08-07
• Study First Posted: 2017-08-11
• Primary Completion: 2017-12-10
• Study Completion: 2017-12-10
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-06
• Last Update Posted: 2018-07-09

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)), 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo Oral Tablet	Placebo, oral tablet in 14 days and in liquid meal.
Saline	Saline	Saline infusion (9mg/mL) on experimental days
Metformin	Metformin	Metformin, oral tablet 2-4 x 500 mg in 14 days and in liquid meal.
Exendin(9-39)	Exendin (9-39)	Exendin(9-39) infusion. GLP-1 receptor antagonist used as a study tool on experimental days.

Primary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Center for Diabetes Research; 🇩🇰 Gentofte, Copenhagen, Denmark