Abstract
Introduction: Metformin (MET) is a 1st choice drug used in patients with type 2 diabetes (DM). Treatment with MET in patient with DM and heart failure (HF) is associated with better cardiovascular outcomes, but mechanisms of MET-mediated effects are unexplained. Our aim was to evaluate the effects of MET on substrate metabolism, cardiac function and structure in patient with DM and HF. Methods: 40 patients with DM and stable chronic HF (age: 59 ± 9 years) were studied in a random sequence cross-over clinical study testing the effect of 3-month usage of MET vs. placebo. The subjects were randomized to MET (2 g/day) or to placebo group. After the three months of treatment the medication was changed and the treatment continued for next 3 months. At the beginning and the end of each intervention period (3 times in total) the panel of various metabolic and cardiovascular tests was done: echocardiography, spiroergometry and meal test with evaluation of several variables like incretins (GLP-1 and peptide YY) and parameters of oxidative stress (MCP-1, TNFα). Results: Compared to placebo, MET was accompanied with significantly higher increase of selected gut-related hormones. GLP-1 area-under-curve increased during the meal test (MET vs. PL: 8571.39±6899.57 vs. 5665.82±4580.57pmol.hour.l-1; p<0.01). Also the peptide YY area-under-curve increased during the meal test (MET vs. PL: 29809.67±13442.43 vs. 23636.21±8183.08pmol.hour.l-1; p<0.05). MCP-1 showed inconsistent trend to increase during meal test. Fasted levels of TNFα were higher after MET, but there was no change during the meal test compared to placebo. MET therapy led to reduction of HbA1C (p<0.001) and reduced glucose area-under-curve (p<0.001) during glucose tolerance test. MET had neutral effect on cardiac structure and function. Conclusions: Our results suggest that metabolic effects of MET might be mediated by improvement of gut endocrine function. MET had neutral effect on cardiac function or structure. Disclosure E. Stolarikova: None. J. Kopecky: None. J. Veleba: None. K. Velebova: None. L. Belinova: None. V. Melenovsky: None. J. Kopecky: None. T. Pelikanova: None.
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