SGLT2 inhibitors and cardiac remodelling: a systematic review and meta-analysis of randomized cardiac magnetic resonance imaging trials

Aims Recent large randomized controlled trials (RCTs) have demonstrated efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in both preventing and treating heart failure (HF). SGLT2i-induced reversal of left ventricular remodelling has been proposed as a mechanism contributing to this effect. Methods and results We performed a systematic review and meta- analysis of RCTs to compare SGLT2i versus placebo (treatment duration >3 months) on cardiac remodelling parameters as measured by cardiac magnetic resonance imaging (cMRI) in patients with HF and/or diabetes. The PubMed and ClinicalTrials. gov databases were searched until 15 June 2021. Our primary outcome was change in absolute left ventricular mass (LVM) from baseline to study endpoint. Secondary outcomes included changes in LVM indexed to body surface area, left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF) from baseline to study endpoint. The Cochrane Collaboration's tool was used to assess risk of bias. Five studies representing 408 patients were included. SGLT2i was associated with greater LVM regression compared to placebo (MD, -5.76 g; 95% CI, -10.87 g to -0.64 g, I-2 = 73%; overall effect, P < 0.03; four RCTs). Statistical subgroup differences were not observed in our sensitivity analysis focusing on HF with reduced ejection fraction (P = 0.37) and were observed in our sensitivity analysis focusing on diabetes (P < 0.001). SGLT2i was not associated with statistical changes in LV mass indexed to body surface area (I-2 = 75%; P = 0.16; five RCTs), LVESV (I-2 = 87%; P = 0.07; five RCTs), LVEDV (I-2 = 81%; P = 0.20; five RCTs), nor LVEF (I-2 = 85%; P = 0.19; five RCTs) versus placebo. Sixty per cent of RCTs had low risk of bias. Conclusions Sodium-glucose cotransporter-2 inhibitors treatment was associated with a reduction in left ventricular mass as assessed by cMRI.