Clinical trial NCT01729156: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Dyslipidemia
Keywords: Type 2 diabetes
Hepatic fatty acid oxidation
Dyslipidemia
Metformin
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2012-11-20
Enrollment: 36
Sex: ALL
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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


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)

Primary outcomes:
measure: Hepatic Fatty Acid Oxidation
timeFrame: 90 days
measure: Hepatic Fatty Acid Reesterification
timeFrame: 90 days
measure: Hepatic Fatty Acid Uptake
timeFrame: 90 days
measure: VLDL-TG Secretion
timeFrame: 90 days
measure: Whole Body Glucose Rd
timeFrame: 90 days
Secondary outcomes:
measure: Fatty Acid Turnover
timeFrame: 90 days
measure: VLDL-TG Oxidation
timeFrame: 90 days
Other outcomes:
Locations:
Study officials:
affiliation: Aarhus University Hospital
name: Lars C Gormsen, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.