METABOLIC EFFECTS OF METFORMIN IN CHRONIC HEART FAILURE PATIENTS ARE MEDIATED BY GUT INCRETIN RELEASE: RANDOMIZED, DOUBLE-BLINDED, PLACEBO-CONTROLLED CROSS-OVER STUDY
Tématický okruh: Srdeční selhání, transplantace, oběhové podpory | |
| Typ: Ústní sdělení - lékařské , Číslo v programu: 670 | |
| Melenovský V.1, Stoláriková E.2, Bělinová L.3, Velebova K.3, Segetová M.1, Kuda O.4, Kopecký J.4, Pelikánová T.5 1 Klinika kardiologie, IKEM, Praha, 2 klinika diabetologie, IKEM, Praha, 3 klinika diabetologie, IKEM, 4 Fyziologický Ústav, Akademie věd ČR, Praha, 5 Centrum diabetologie, IKEM, Praha | |
Introduction: In observational studies, Metformin (MET) use in HF patients is associated with better survival, but mechanisms are unexplained. We hypothesized that effects of MET, poorly absorbed drug, can be mediated by affecting gut microbial or endocrine function. Methods: 40 patients with chronic stable HFrEF (LV EF 32±9%) and untreated T2DM (HbA1C% 46±8 mmol/mol) were studied in a double-blinded random sequence cross-over study. At 3 visits, patients underwent cardiovascular function testing, CPX and body composition. Intestinal microbiome marker – circulating trimethylamine-N-oxide (TMAO), was quantified by LCMS. Gut-derived hormones Glucagone-like peptide 1 (GLP-1) and peptide YY (PYY) were measured at fasted state and after a standartized meal. Patients were studied at baseline, after 3 months of placebo or after metformin (2000 mg once daily) in addition to standard HF therapy. No other DM intervention was used. Results: There was a trend to lower BMI on MET. Compared to placebo, MET had no effect on body composition (DEXA), cardiac structure, function, exercise capacity (peak VO2) or BNP levels, probably due to too short duration of intervention. MET therapy led to reduction of HbA1C , reduced glucose (p˂0.001) and insulin (p=0.01) AUC during oral glucose tolerance test. After a test meal, MET-treated HF patients had highly significant postprandial increase of gut-related hormones GLP-1 and peptide YY, compared to placebo, change of insulin was relatively modest. TMAO level tended to be higher after MET than after placebo. Conclusions: Short-term therapy with MET in patients with HF and DM had neutral effects on cardiovascular structure and function, but favorably modified substrate metabolism. Results indicate that metabolic effects of MET are mediated in part by improvement of gut endocrine function and by enhancement of GLP-1 release. | |
