Protective Effect of SGLT2 Inhibitors on Heart Muscle Function - Findings from a Recent Meta-analysis
Sodium-glucose cotransporter 2 inhibitors (SGLT2i, i.e., gliflozins) primarily offer the ability to achieve very good glycemic control with a low risk of hypoglycemia. Their undeniable advantage, however, is their cardiovascular safety and renoprotective effect. The impact of gliflozins on heart functions has already been the subject of many studies, the findings of which are summarized in a recently published meta-analysis.
Mechanism of Cardioprotection
The positive cardiorenal outcomes of gliflozin use have been highlighted by the results of recent large randomized controlled trials. Patients on these medications have shown a reduced risk of hospitalization for heart failure, and this reduction was observed independent of the presence of diabetes mellitus in the patients' histories. The exact mechanism of the cardioprotective effects of gliflozins, however, has yet to be clarified. Experimental studies have suggested a possible direct effect on cardiomyocytes. Other processes to some extent influenced by SGLT2i include changes in intracellular ion levels, energy metabolism, inflammatory processes in myocardial cells, increased fibrosis, and remodeling of the heart muscle. Additionally, gliflozins may reduce the incidence of atrial fibrillation.
Analyzed Data
The analysis included a total of 32 studies with 2351 patients. The monitored markers of heart functions included several parameters detectable primarily through echocardiographic examination and magnetic resonance imaging, specifically left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular mass index to body surface area (LVMi), left atrial volume index to body surface area (LAVi), and the E/e´ ratio (where E is the peak filling velocity of the LV in early diastole and e´ is the peak velocity of the movement of the mitral annulus in early diastole), which suitably correlates with wedge pressure values (otherwise only determinable by invasive methods).
Findings
According to the results of the meta-analysis, gliflozin use led to an increase in LVEF in patients at different stages of heart failure (mean difference [MD] 1.97; 95% confidence interval [CI] 0.92−3.02; p < 0.01; I2 = 84%), with a concurrent increase in GLS (MD 1.17; 95% CI 0.25−2.10; p < 0.01).
Furthermore, there was a decrease in LVESV (MD −3.60; 95% CI −7.20 to −0.18; p = 0.04; I2 = 9%), while the effect on LVEDV was neutral (MD −3.10; 95% CI −6.76 to 0.56; p = 0.40; I2 = 4%).
Other monitored parameters were significantly reduced: LVMi (MD −3.99; 95% CI −7.16 to −0.82; p = 0.01; I2 = 65%), LAVi (MD −1.77; 95% CI −2.97 to −0.57; p < 0.01; I2 = 0%), and E/e´ ratio (MD −1.39; 95% CI −2.04 to −0.73; p < 0.01; I2 = 55%).
Conclusion
The results of the recent meta-analysis pointed to the significant cardioprotective effect of SGLT2 inhibitors in patients with heart failure. The effects were demonstrated in both diabetic patients and those not treated for diabetes with a primary diagnosis of heart failure. Improvement in LVEF was more pronounced in studies with empagliflozin in patients with heart failure. By suppressing myocardial remodeling and simultaneously inducing reverse remodeling, they improve the prognosis of patients and reduce the risk of hospitalization for cardiovascular events. The mechanisms by which gliflozins achieve cardioprotective effects likely combine, and further experimental and clinical research will be necessary for their full elucidation.
(kali)
Source: Theofilis P., Antonopoulos A. S., Katsimichas T. The impact of SGLT2 inhibition on imaging markers of cardiac function: a systematic review and meta-analysis. Pharmacol Res 2022 Jun; 180: 106243, doi: 10.1016/j.phrs.2022.106243.
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.
