Effects of Metformin on Hepatic FFA Metabolism

September 24, 2019 updated by: Lars Christian Gormsen

Effects of Metformin on Hepatic Free Fatty Acid Metabolism in Patients Diagnosed With Type 2 Diabetes: A C11 PET Study

Background: Metformin treatment has beneficial effects on both glucose and lipid metabolism. Whereas there is general agreement that the blood glucose lowering effect of metformin results from inhibition of hepatic gluconeogenesis, it is less clear exactly how the drug lowers blood triglyceride concentration. There are indications that it enhances hepatic free fatty acid (FFA) oxidation thus diminishing substrate for reesterification and resecretion as very-low-density-lipoprotein (VLDL) triglycerides (TG). However, the liver is not easily accessible for sampling in humans and data on the clinical effects of metformin in the liver are therefore lacking. This may change due to the increasing use of the positron emission tomography (PET) technique. Using PET isotopes (11C or 18F) coupled to either palmitate or a fatty acid analogue, it is possible to non-invasively measure hepatic fatty acid handling.

Aim: To determine how 3 months metformin treatment (1000 mg twice daily) affects hepatic lipid and glucose metabolism in patients with newly diagnosed type 2 diabetes.

Design: Randomized, placebo controlled, double-blind parallel study with patients receiving either metformin or placebo. A control group of BMI and age-matched non-diabetic individuals will receive metformin for 3 months.

Hypothesis: Metformin lowers VLDL-TG secretion and circulating triglycerides by increasing hepatic fatty acid oxidation

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Recently diagnosed type 2 diabetes
  • Age 50-70 years
  • BMI<40

Exclusion Criteria:

  • Insulin treatment
  • NASH (non alcoholic steatohepatitis)
  • Cancer
  • Anemia
  • HbA1C>8.5 %
  • Chronic or acute pancreatitis
  • Alcohol or medicine abuse
  • Allergy towards metformin
  • Claustrophobia
  • Severe obesity (weight >130 kilogram)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
2 tablets twice daily in 3 months
Other: Healthy controls
Healthy controls receiving 1000 mg metformin twice daily for 3 months
Drug: Metformin
1000 mg metformin twice daily in 3 months
Other Names:
  • Metformin "Sandoz" 500 mg
Active Comparator: Metformin
Metformin "Sandoz", 1000 mg twice daily for 3 months
Drug: Metformin
1000 mg metformin twice daily in 3 months
Other Names:
  • Metformin "Sandoz" 500 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hepatic Fatty Acid Oxidation
Time Frame: 90 days
Hepatic fatty acid oxidation assessed by dynamic C11-palmitate PET
90 days
Hepatic Fatty Acid Reesterification
Time Frame: 90 days
Hepatic fatty acid reesterification assessed by C11-palmitate PET
90 days
Hepatic Fatty Acid Uptake
Time Frame: 90 days
Hepatic fatty acid uptake assessed by C11-palmitate PET
90 days
VLDL-TG Secretion
Time Frame: 90 days
Hepatic VLDL-TG secretion assessed by [1-14C] VLDL tracer
90 days
Whole Body Glucose Rd
Time Frame: 90 days
Whole body basal glucose metabolism assessed by [3-3H]glucose tracer kinetics
90 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fatty Acid Turnover
Time Frame: 90 days
Fatty acid turnover assessed as whole body C11-palmitate turnover
90 days
VLDL-TG Oxidation
Time Frame: 90 days
VLDL-TG oxidation assessed by 14C carbon dioxide (CO2) in exhaled breath
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lars Christian Gormsen

Investigators

  • Principal Investigator: Lars C Gormsen, MD PhD, Aarhus University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Actual)

May 5, 2017

Study Completion (Actual)

May 5, 2017

Study Registration Dates

First Submitted

November 13, 2012

First Submitted That Met QC Criteria

November 13, 2012

First Posted (Estimate)

November 20, 2012

Study Record Updates

Last Update Posted (Actual)

October 15, 2019

Last Update Submitted That Met QC Criteria

September 24, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C11palmitatMetformin

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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