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Metformin does not affect postabsorptive hepatic free fatty acid uptake, oxidation or resecretion in humans: A 3‐month placebo‐controlled clinical trial in patients with type 2 diabetes and healthy controls
Author(s) -
Gormsen Lars C.,
Søndergaard Esben,
Christensen Nana L.,
Jakobsen Steen,
Nielsen Erik H. T.,
Munk Ole L.,
Tolbod Lars P.,
Jessen Niels,
Nielsen Søren
Publication year - 2018
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13244
Subject(s) - metformin , medicine , placebo , endocrinology , type 2 diabetes , fatty acid , lipid metabolism , carbohydrate metabolism , diabetes mellitus , chemistry , biochemistry , pathology , alternative medicine
Aims To explore whether the pre‐clinical findings that metformin improves lipid metabolism, possibly through modulation of intrahepatic partitioning of fatty acids towards oxidation and away from re‐esterification and resecretion as triglycerides (TGs), can be translated to a human setting. Materials and methods We performed a 3‐month randomized, placebo‐controlled, parallel‐group clinical trial in patients with type 2 diabetes (T2D; n = 24) and healthy controls ( n = 12). Patients with T2D received either placebo (placebo group) or 1000 mg metformin twice daily (metformin group), while healthy subjects were all treated with metformin (control group). Hepatic fatty acid metabolism was measured by [ 11 C]palmitate positron‐emission tomography, hepatic TG secretion and peripheral oxidation by ex vivo labelled [1‐ 14 C]VLDL‐TG and VLDL particle size by TG/apolipoprotein B ratio. Body composition was assessed by dual‐energy X‐ray and whole‐body lipid oxidation by indirect calorimetry. Results Metformin treatment for 3 months produced the anticipated decrease in fasting plasma glucose (FPG) in the metformin group (FPG 7.9 ± 1.8 mM [study day 1] vs 6.4 ± 1.1 mM [study day 2]), whereas patients in the placebo group and healthy controls had similar FPG levels before and after the trial (mixed model group vs time interaction; P = .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.