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

Primary Purpose

Glucose Metabolism Disorders

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Placebo Oral Tablet
Metformin
Saline
Exendin (9-39)
Sponsored by
University Hospital, Gentofte, Copenhagen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Glucose Metabolism Disorders focused on measuring GLP-1, glucagon-like peptide-1, Metformin, Exendin(9-39)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Center for Diabetes Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Arm Label

Placebo

Metformin

Saline

Exendin(9-39)

Arm Description

Placebo, oral tablet in 14 days and in liquid meal.

Metformin, oral tablet 2-4 x 500 mg in 14 days and in liquid meal.

Saline infusion (9mg/mL) on experimental days

Exendin(9-39) infusion. GLP-1 receptor antagonist used as a study tool on experimental days.

Outcomes

Primary Outcome Measures

Plasma glucose
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.

Secondary Outcome Measures

Full Information

First Posted
August 1, 2017
Last Updated
July 6, 2018
Sponsor
University Hospital, Gentofte, Copenhagen
Collaborators
University of Copenhagen
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1. Study Identification

Unique Protocol Identification Number
NCT03246451
Brief Title
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

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
July 1, 2017 (Actual)
Primary Completion Date
December 10, 2017 (Actual)
Study Completion Date
December 10, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Gentofte, Copenhagen
Collaborators
University of Copenhagen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glucose Metabolism Disorders
Keywords
GLP-1, glucagon-like peptide-1, Metformin, Exendin(9-39)

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo, oral tablet in 14 days and in liquid meal.
Arm Title
Metformin
Arm Type
Experimental
Arm Description
Metformin, oral tablet 2-4 x 500 mg in 14 days and in liquid meal.
Arm Title
Saline
Arm Type
Experimental
Arm Description
Saline infusion (9mg/mL) on experimental days
Arm Title
Exendin(9-39)
Arm Type
Experimental
Arm Description
Exendin(9-39) infusion. GLP-1 receptor antagonist used as a study tool on experimental days.
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Intervention Description
2-4 tablets in 14 days
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
1000-2000 mg in 14 days
Intervention Type
Drug
Intervention Name(s)
Saline
Intervention Description
9 mg/ml saline infusion during experimental days
Intervention Type
Drug
Intervention Name(s)
Exendin (9-39)
Intervention Description
Infusion of GLP-1 receptor antagonist used as a tool during experimental days
Primary Outcome Measure Information:
Title
Plasma glucose
Description
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.
Time Frame
Minutes 240

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Filip K Knop, MD, PhD
Organizational Affiliation
UHGentofte, Center for Diabetes Research
Official's Role
Study Director
Facility Information:
Facility Name
Center for Diabetes Research
City
Gentofte
State/Province
Copenhagen
ZIP/Postal Code
2900
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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