Glucose Metabolism Disorders
Conditions
Keywords
GLP-1, glucagon-like peptide-1, Metformin, Exendin(9-39)
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.
Interventions
DRUGPlacebo Oral Tablet
2-4 tablets in 14 days
DRUGMetformin
1000-2000 mg in 14 days
DRUGSaline
9 mg/ml saline infusion during experimental days
DRUGExendin (9-39)
Infusion of GLP-1 receptor antagonist used as a tool during experimental days
Sponsors
University of Copenhagen
University Hospital, Gentofte, Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Denmark
Outcome results
None listed