Effects of Metformin on Hepatic FFA Metabolism

Type 2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01729156
• Other study ID #: C11palmitatMetformin
• Status: Completed
• Phase: Phase 4
• Start date: January 2013
• Est. completion date: May 5, 2017

Study information

• Verified date: September 2019
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: May 5, 2017
• Est. primary completion date: May 5, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Dyslipidemia
• Dyslipidemias
• Type 2 Diabetes

Intervention

Drug:
• Metformin
1000 mg metformin twice daily in 3 months
• Placebo
2 tablets twice daily in 3 months

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Lars Christian Gormsen

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hepatic Fatty Acid Oxidation	Hepatic fatty acid oxidation assessed by dynamic C11-palmitate PET	90 days
Primary	Hepatic Fatty Acid Reesterification	Hepatic fatty acid reesterification assessed by C11-palmitate PET	90 days
Primary	Hepatic Fatty Acid Uptake	Hepatic fatty acid uptake assessed by C11-palmitate PET	90 days
Primary	VLDL-TG Secretion	Hepatic VLDL-TG secretion assessed by [1-14C] VLDL tracer	90 days
Primary	Whole Body Glucose Rd	Whole body basal glucose metabolism assessed by [3-3H]glucose tracer kinetics	90 days
Secondary	Fatty Acid Turnover	Fatty acid turnover assessed as whole body C11-palmitate turnover	90 days
Secondary	VLDL-TG Oxidation	VLDL-TG oxidation assessed by 14C carbon dioxide (CO2) in exhaled breath	90 days