Clinical trial NCT03246451: The Role of GLP-1 Receptor Signalling in the Glucose-lowering Effect of Metformin in Patients With T2D
Official title: The Role of GLP-1 Receptor Signalling in the Glucose-lowering Effect of Metformin During Meal Ingestion in Patients With T2D
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glucose Metabolism Disorders
Keywords: GLP-1
glucagon-like peptide-1
Metformin
Exendin(9-39)
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
First posted: 2017-08-11
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Plasma glucose
timeFrame: Minutes 240
Secondary outcomes:
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Center for Diabetes Research
state: Copenhagen
Study officials:
affiliation: UHGentofte, Center for Diabetes Research
name: Filip K Knop, MD, PhD
role: STUDY_DIRECTOR
References: