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Effects of Metformin on Hepatic FFA Metabolism

Primary Purpose

Type 2 Diabetes, Dyslipidemia

Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Metformin
Placebo
Sponsored by
Lars Christian Gormsen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Type 2 Diabetes focused on measuring Type 2 diabetes, Hepatic fatty acid oxidation, Dyslipidemia, Metformin

Eligibility Criteria

50 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Other

    Placebo Comparator

    Active Comparator

    Arm Label

    Healthy controls

    Placebo

    Metformin

    Arm Description

    Healthy controls receiving 1000 mg metformin twice daily for 3 months

    Placebo

    Metformin "Sandoz", 1000 mg twice daily for 3 months

    Outcomes

    Primary Outcome Measures

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

    Secondary Outcome Measures

    Fatty Acid Turnover
    Fatty acid turnover assessed as whole body C11-palmitate turnover
    VLDL-TG Oxidation
    VLDL-TG oxidation assessed by 14C carbon dioxide (CO2) in exhaled breath

    Full Information

    First Posted
    November 13, 2012
    Last Updated
    September 24, 2019
    Sponsor
    Lars Christian Gormsen
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01729156
    Brief Title
    Effects of Metformin on Hepatic FFA Metabolism
    Official Title
    Effects of Metformin on Hepatic Free Fatty Acid Metabolism in Patients Diagnosed With Type 2 Diabetes: A C11 PET Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2019
    Overall Recruitment Status
    Completed
    Study Start Date
    January 2013 (undefined)
    Primary Completion Date
    May 5, 2017 (Actual)
    Study Completion Date
    May 5, 2017 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Lars Christian Gormsen

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Type 2 Diabetes, Dyslipidemia
    Keywords
    Type 2 diabetes, Hepatic fatty acid oxidation, Dyslipidemia, Metformin

    7. Study Design

    Primary Purpose
    Basic Science
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    36 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Healthy controls
    Arm Type
    Other
    Arm Description
    Healthy controls receiving 1000 mg metformin twice daily for 3 months
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo
    Arm Title
    Metformin
    Arm Type
    Active Comparator
    Arm Description
    Metformin "Sandoz", 1000 mg twice daily for 3 months
    Intervention Type
    Drug
    Intervention Name(s)
    Metformin
    Other Intervention Name(s)
    Metformin "Sandoz" 500 mg
    Intervention Description
    1000 mg metformin twice daily in 3 months
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    2 tablets twice daily in 3 months
    Primary Outcome Measure Information:
    Title
    Hepatic Fatty Acid Oxidation
    Description
    Hepatic fatty acid oxidation assessed by dynamic C11-palmitate PET
    Time Frame
    90 days
    Title
    Hepatic Fatty Acid Reesterification
    Description
    Hepatic fatty acid reesterification assessed by C11-palmitate PET
    Time Frame
    90 days
    Title
    Hepatic Fatty Acid Uptake
    Description
    Hepatic fatty acid uptake assessed by C11-palmitate PET
    Time Frame
    90 days
    Title
    VLDL-TG Secretion
    Description
    Hepatic VLDL-TG secretion assessed by [1-14C] VLDL tracer
    Time Frame
    90 days
    Title
    Whole Body Glucose Rd
    Description
    Whole body basal glucose metabolism assessed by [3-3H]glucose tracer kinetics
    Time Frame
    90 days
    Secondary Outcome Measure Information:
    Title
    Fatty Acid Turnover
    Description
    Fatty acid turnover assessed as whole body C11-palmitate turnover
    Time Frame
    90 days
    Title
    VLDL-TG Oxidation
    Description
    VLDL-TG oxidation assessed by 14C carbon dioxide (CO2) in exhaled breath
    Time Frame
    90 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    50 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    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)
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Lars C Gormsen, MD PhD
    Organizational Affiliation
    Aarhus University Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    30976851
    Citation
    Gormsen LC, Sondergaard E, Christensen NL, Brosen K, Jessen N, Nielsen S. Metformin increases endogenous glucose production in non-diabetic individuals and individuals with recent-onset type 2 diabetes. Diabetologia. 2019 Jul;62(7):1251-1256. doi: 10.1007/s00125-019-4872-7. Epub 2019 Apr 11.
    Results Reference
    derived

    Learn more about this trial

    Effects of Metformin on Hepatic FFA Metabolism

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