Effect of sodium-glucose cotransporter-2 inhibitors on cardiac remodelling: a systematic review and meta-analysis

Aims
To examine the effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cardiac remodelling in patients with type 2 diabetes mellitus (T2DM) and/or heart failure (HF), and to explore the subsets of patients who may have greater benefit from SGLT2i therapy.

Methods and results
Four electronic databases were searched for randomized controlled trials (RCTs) that evaluated the effects of SGLT2i on parameters reflecting cardiac remodelling in patients with T2DM and/or HF. Standardized mean differences (SMDs) or mean differences (MDs) were pooled. Subgroup analyses were performed according to the baseline HF and T2DM, HF type, SGLT2i agent, follow-up duration, and imaging modality. A total of 13 RCTs involving 1251 patients were analysed. Sodium-glucose cotransporter-2 inhibitors treatment significantly improved left ventricular (LV) ejection fraction [SMD, 0.35; 95% confidence interval (CI) (0.04, 0.65); P = 0.03], LV mass [SMD, −0.48; 95% CI (−0.79, −0.18); P = 0.002], LV mass index [SMD, −0.27; 95% CI (−0.49, −0.05); P = 0.02], LV end-systolic volume [SMD, −0.37; 95% CI (−0.71; −0.04); P = 0.03], LV end-systolic volume index [MD, −0.35 mL/m2; 95% CI (−0.64, −0.05); P = 0.02], and E-wave deceleration time [SMD, −0.37; 95% CI (−0.70, −0.05); P = 0.02] in the overall population. Subgroup analyses showed that the favourable effects of SGLT2i on LV remodelling were only significant in HF patients, especially HF with reduced ejection fraction (HFrEF), regardless of glycaemic status. Among the four included SGLT2i, empagliflozin was associated with a greater improvement of LV mass, LV mass index, LV end-systolic volume, LV end-systolic volume index, LV end-diastolic volume, and LV end-diastolic volume index (all P < 0.05).

Conclusions
Sodium-glucose cotransporter-2 inhibitors treatment significantly reversed cardiac remodelling, improving LV systolic and diastolic function, LV mass and volume, especially in patients with HFrEF and amongst those taking empagliflozin compared with other SGLT2i. Reversed remodelling may be a mechanism responsible for the favourable clinical effects of SGLT2i on HF.