Effects of Metformin on Hepatic FFA Metabolism

Lars Christian Gormsen

Status and phase: Completed; Phase 4

Conditions: Dyslipidemia; Type 2 Diabetes

Treatments: Drug: Metformin; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01729156

C11palmitatMetformin

Details and patient eligibility

About

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

Enrollment: 36 patients

Sex: All

Ages: 50 to 70 years old

Volunteers: Accepts 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)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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36 participants in 3 patient groups, including a placebo group

Healthy controls

Other group

Description:

Healthy controls receiving 1000 mg metformin twice daily for 3 months

Treatment:

Drug: Metformin

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Placebo

Metformin

Active Comparator group

Description:

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

Treatment:

Drug: Metformin