Effect of Extended Release Metformin on Cardiometabolic Parameters in Рatients with Prediabetes, Chronic Heart Failure, and Abdominal Obesity (12-Month Follow-Up)

Aim. To study the effect of extended-release (XR) metformin after 12 months of use on humoral cardiometabolic markers, parameters of lipid peroxidation (LPO) and vascular stiffness in patients with chronic heart failure with preserved ejection fraction (CHpEF), prediabetes and abdominal obesity (AO).

Design. A single-center, open-label, randomized, controlled clinical trial.

Materials and methods. The PredMet study included 64 patients (50% men) with CHpEF, prediabetes, and AO. The patients were divided into two groups: group A — metformin XR at a dose of 1000–1500 mg per day for 12 months on the background of standard CHpEF therapy; group B — standard CHpEF therapy. Humoral cardiometabolic parameters (levels of the soluble form of interleukin 33 receptor (soluble ST2), N-terminal propeptide of natriuretic hormone (NT-proBNP), highly sensitive C-reactive protein, hs CRP), oxidative stress parameters (baseline level of malondialdehyde (MDA) in low-density lipoproteins (LDL) and their resistance to oxidation) and the radial augmentation index.

Results. After 12 months of the main follow-up period in group A, the level of NT-proBNP decreased by 1.5% (p = 0.007), and the serum hs CRP decreased by 20.7% (p = 0.021) from the baseline values. The concentration of MDA, estimated directly in LDL, when taking metformin XR against the background of standard CHpEF therapy decreased by 4% (p = 0.018), and the content of MDA in LDL after incubation with copper ions decreased by 0.3% (p = 0.035). In group B, on the contrary, there was an increase in the basal level of MDA in LDL by 0.7% (p = 0.044) and its value after incubation of LDL with copper ions by 6.1% (p = 0.009). The levels of soluble ST2 and the radial augmentation index did not differ at visits 1 and 3 in both groups.

Conclusion. Taking metformin XR for 12 months at a dose of 1000–1500 mg per day in addition to standard CHpEF therapy in patients with prediabetes and AO is associated with a decrease in markers of inflammation and LPO, as well as a decrease in the level of NT-proBNP. 

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