Long-term effects of metformin on fat depots and insulin-glucose parameters in patients with prediabetes and chronic heart failure

Introduction . Chronic heart failure with preserved ejection fraction (CHpEF) is a heterogeneous syndrome with a variety of pathophysiological factors, including obesity and impaired carbohydrate metabolism associated with an increase in visceral adipose tissue. Due to the positive effect of metformin on weight loss, in recent years special attention has been paid to its effect on fat depots. Aim . To study the effects of metformin XR after 12 months of administration on various fat depots and glucose metabolism parameters in patients with CHpEF, prediabetes and abdominal obesity (AO). Materials and methods . A single-center open-label randomized prospective controlled trial included 64 people (50% men, median age 58 [55.25; 59.75] years) with CHpEF, prediabetes and AO. All patients (groups A and B) received optimal CHpEF therapy. In group A (n = 32), metformin XR 1000–1500 mg/day was additionally prescribed. All patients underwent general clinical examination, calculation of insulin resistance indices, ultrasound lipometry with determination of the size of epicardial, preperitoneal and subcutaneous fat, in addition, the thickness of epicardial fat was assessed using magnetic resonance imaging (MRI) of the heart. Results . In group A, after 12 months of the study, fasting plasma glucose levels decreased from baseline by 7.7% (p < 0.0001), glycated hemoglobin by 3.3% (p = 0.008), fasting insulin by 20% (p = 0.004) and HOMA-IR and FIRI indices by 25.3% (p = 0.001). In the control group, on the contrary, the values of glycated hemoglobin increased by 3.4% (p = 0.021), fasting insulin by 45% (p = 0.031), HOMA-IR and FIRI by 52.4% (p = 0.020). In group A, the thickness of epicardial fat decreased by 6.1% (p = 0.020) according to ultrasound and MRI lipometry by 16.7% (p = 0.029), preperitoneal fat by 3.0% (p = 0.009), subcutaneous fat by 11.2% (p = 0.001). Conclusion . Metformin XR therapy for 12 months in patients with prediabetes, CHpEF and AO against the background of optimal basic CHpEF therapy had a beneficial effect on glucose metabolism (decrease in fasting plasma glucose and insulin, glycated hemoglobin, insulin resistance indices HOMA-IR, FIRI) and on subcutaneous and visceral adipose tissue depots: epicardial and preperitoneal.