Effects of Metformin on Hepatic FFA Metabolism
Overview[ - collapse ][ - ]
Purpose | 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 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 healthy controls will receive metformin for 3 months. Hypothesis: Metformin lowers VLDL-TG secretion and circulating triglycerides by increasing hepatic fatty acid oxidation |
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Condition | Type 2 Diabetes Dyslipidemia |
Intervention | Drug: Metformin Drug: Placebo |
Phase | Phase 4 |
Sponsor | Lars Christian Gormsen |
Responsible Party | University of Aarhus |
ClinicalTrials.gov Identifier | NCT01729156 |
First Received | November 13, 2012 |
Last Updated | November 26, 2012 |
Last verified | November 2012 |
Tracking Information[ + expand ][ + ]
First Received Date | November 13, 2012 |
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Last Updated Date | November 26, 2012 |
Start Date | January 2013 |
Estimated Primary Completion Date | April 2016 |
Current Primary Outcome Measures |
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Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
Brief Title | Effects of Metformin on Hepatic FFA Metabolism |
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Official Title | Effects of Metformin on Hepatic Free Fatty Acid Metabolism in Patients Diagnosed With Type 2 Diabetes: A C11 PET Study |
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 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 healthy controls will receive metformin for 3 months. Hypothesis: Metformin lowers VLDL-TG secretion and circulating triglycerides by increasing hepatic fatty acid oxidation |
Detailed Description | Not Provided |
Study Type | Interventional |
Study Phase | Phase 4 |
Study Design | Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science |
Condition |
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Intervention | Drug: Metformin Other Names: Metformin "Sandoz" 500 mgDrug: Placebo |
Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
Recruitment Status | Not yet recruiting |
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Estimated Enrollment | 36 |
Estimated Completion Date | April 2016 |
Estimated Primary Completion Date | July 2015 |
Eligibility Criteria | Inclusion Criteria: - Newly diagnosed type 2 diabetes (>3 and <12 months) - Age 50-70 years - BMI<40 Exclusion Criteria: - Metformin treatment >6 months - 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) |
Gender | Both |
Ages | 50 Years |
Accepts Healthy Volunteers | Accepts Healthy Volunteers |
Contacts | Contact: Lars C Gormsen, MD PhD +4578456205 lars.christian.gormsen@ki.au.dk |
Location Countries | Not Provided |
Administrative Information[ + expand ][ + ]
NCT Number | NCT01729156 |
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Other Study ID Numbers | C11palmitatMetformin |
Has Data Monitoring Committee | Yes |
Information Provided By | University of Aarhus |
Study Sponsor | Lars Christian Gormsen |
Collaborators | Not Provided |
Investigators | Principal Investigator: Lars C Gormsen, MD PhD Aarhus University Hospital |
Verification Date | November 2012 |