Effects of Metformin on Hepatic FFA Metabolism
1 other identifier
interventional
36
0 countries
N/A
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_4 type-2-diabetes
Started Jan 2013
Longer than P75 for phase_4 type-2-diabetes
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 13, 2012
CompletedFirst Posted
Study publicly available on registry
November 20, 2012
CompletedStudy Start
First participant enrolled
January 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 5, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
May 5, 2017
CompletedResults Posted
Study results publicly available
October 15, 2019
CompletedOctober 15, 2019
September 1, 2019
4.3 years
November 13, 2012
September 24, 2019
September 24, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Hepatic Fatty Acid Oxidation
Hepatic fatty acid oxidation assessed by dynamic C11-palmitate PET
90 days
Hepatic Fatty Acid Reesterification
Hepatic fatty acid reesterification assessed by C11-palmitate PET
90 days
Hepatic Fatty Acid Uptake
Hepatic fatty acid uptake assessed by C11-palmitate PET
90 days
VLDL-TG Secretion
Hepatic VLDL-TG secretion assessed by \[1-14C\] VLDL tracer
90 days
Whole Body Glucose Rd
Whole body basal glucose metabolism assessed by \[3-3H\]glucose tracer kinetics
90 days
Secondary Outcomes (2)
Fatty Acid Turnover
90 days
VLDL-TG Oxidation
90 days
Study Arms (3)
Healthy controls
OTHERHealthy controls receiving 1000 mg metformin twice daily for 3 months
Placebo
PLACEBO COMPARATORPlacebo
Metformin
ACTIVE COMPARATORMetformin "Sandoz", 1000 mg twice daily for 3 months
Interventions
Eligibility Criteria
You may qualify if:
- Recently diagnosed type 2 diabetes
- Age 50-70 years
- BMI\<40
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Related Publications (1)
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.
PMID: 30976851DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Lars C. Gormsen, Consultant
- Organization
- Department of Nuclear Medicine & PET Centre, Aarhus University Hospital
Study Officials
- PRINCIPAL INVESTIGATOR
Lars C Gormsen, MD PhD
Aarhus University Hospital
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Senior Registrar, MD PhD
Study Record Dates
First Submitted
November 13, 2012
First Posted
November 20, 2012
Study Start
January 1, 2013
Primary Completion
May 5, 2017
Study Completion
May 5, 2017
Last Updated
October 15, 2019
Results First Posted
October 15, 2019
Record last verified: 2019-09