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

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ClinicalTrials.gov Identifier: NCT03246451
Recruitment Status : Recruiting
First Posted : August 11, 2017
Last Update Posted : August 14, 2017
Sponsor:
Collaborator:
University of Copenhagen
Information provided by (Responsible Party):
Laura Smidt Hansen, 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.

Condition or disease Intervention/treatment Phase
Glucose Metabolism Disorders Drug: Placebo Oral Tablet Drug: Metformin Drug: Saline Drug: Exendin (9-39) Not Applicable

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 Type : Interventional  (Clinical Trial)
Estimated 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 : July 1, 2017
Estimated Primary Completion Date : December 10, 2017
Estimated Study Completion Date : December 10, 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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



Primary Outcome Measures :
  1. Plasma glucose [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03246451


Contacts
Contact: Laura S Hansen, BSc +45 38677747 laura.smidt.hansen.02@regionh.dk
Contact: Filip K Knop, MD, PhD filipkknop@dadlnet.dk

Locations
Denmark
Center for Diabetes Research Recruiting
Gentofte, Copenhagen, Denmark, 2900
Contact: Laura S Hansen, BSc       laura.smidt.hansen.02@regionh.dk   
Contact: Filip K Knop, MD, PhD       filipkknop@dadlnet.dk   
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
University of Copenhagen
Investigators
Study Director: Filip K Knop, MD, PhD UHGentofte, Center for Diabetes Research

Responsible Party: Laura Smidt Hansen, Bachelor of Science, University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier: NCT03246451     History of Changes
Other Study ID Numbers: UHG-CFD-METEX
First Posted: August 11, 2017    Key Record Dates
Last Update Posted: August 14, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Laura Smidt Hansen, University Hospital, Gentofte, Copenhagen:
GLP-1
glucagon-like peptide-1
Metformin
Exendin(9-39)

Additional relevant MeSH terms:
Metabolic Diseases
Glucose Metabolism Disorders
Metformin
Glucagon-Like Peptide 1
Glucagon
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Gastrointestinal Agents