Erik Nguyen Nielsen

AIMS: Metformin is due to its well-documented glucose lowering effect the most commonly used drug in patients with T2D. However, metformin have also in pre-clinical studies been shown to improve lipid metabolism, possibly through modulation of intrahepatic partitioning of fatty acids towards oxidation and away from reesterification and resecretion as triglycerides.

MATERIALS AND METHODS: To explore whether these pre-clinical findings can be translated to a human setting, we performed a 3-month randomized, placebo controlled, parallel-group clinical trial in patients with T2D (24 patients) and healthy controls (12 subjects). T2D subjects received either placebo (PLA) or 1000 mg metformin bid. (MET) whereas healthy subjects were all treated with metformin (CONT). Hepatic fatty acid metabolism was measured by [11C]palmitate PET, hepatic triglyceride secretion and peripheral oxidation by ex-vivo labelled [1-14C]VLDL-TG and VLDL-particle size by TG/ApoB ratio. Body composition was assessed by DXA and whole body lipid oxidation by indirect calorimetry.

RESULTS: Metformin treatment for three months produced the anticipated decrease in FPG in the MET group [FPG (mM): 7.9±1.8 (study day 1) vs. 6.4±1.1 (study day 2)] whereas patients in the PLA group and healthy controls had similar FPG levels before and after the trial (mixed model group vs. time interaction, p=0.003). However, contrary to our hypothesis, metformin treatment did not affect hepatic lipid metabolism or peripheral oxidation.

CONCLUSION: The observed beneficial effects on lipid metabolism during metformin treatment in humans appear to be secondary to long-term alterations in body composition or glucose homeostasis.