Effect of sodium-glucose cotransporter 2 inhibitors on cardiac structure and function in type 2 diabetes mellitus patients with or without chronic heart failure: a meta-analysis

Abstract

Background: Although the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular events have been reported in patients with type 2 diabetes mellitus (T2DM) with or without heart failure (HF), the impact of SGLT2i on cardiac remodelling remains to be established.

Methods: We searched the PubMed, Embase, Cochrane Library and Web of Science databases up to November 16th, 2020, for randomized controlled trials reporting the effects of SGLT2i on parameters of cardiac structure, cardiac function, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level or the Kansas City Cardiomyopathy Questionnaire (KCCQ) score in T2DM patients with or without chronic HF. The effect size was expressed as the mean difference (MD) or standardized mean difference (SMD) and its 95% confidence interval (CI). Subgroup analyses were performed based on the stage A-B or stage C HF population and HF types.

Results: Compared to placebo or other antidiabetic drugs, SGLT2i showed no significant effects on left ventricular mass index, left ventricular end diastolic volume index, left ventricular end systolic volume index, or left atrial volume index. SGLT2i improved left ventricular ejection fraction only in the subgroup of HF patients with reduced ejection fraction (MD 3.16%, 95% CI 0.11 to 6.22, p = 0.04; I² = 0%), and did not affect the global longitudinal strain in the overall analysis including stage A-B HF patients. SGLT2i showed benefits in the E/e' ratio (MD - 0.45, 95% CI - 0.88 to - 0.03, p = 0.04; I² = 0%), plasma NT-proBNP level (SMD - 0.09, 95% CI - 0.16 to - 0.03, p = 0.004; I² = 0%), and the KCCQ score (SMD 3.12, 95% CI 0.76 to 5.47, p = 0.01; I² = 0%) in the overall population.

Conclusion: The use of SGLT2i was associated with significant improvements in cardiac diastolic function, plasma NT-proBNP level, and the KCCQ score in T2DM patients with or without chronic HF, but did not significantly affect cardiac structural parameters indexed by body surface area. The LVEF level was improved only in HF patients with reduced ejection fraction.

Keywords: Cardiac remodelling; Chronic heart failure; Sodium–glucose cotransporter 2 inhibitors; Type 2 diabetes mellitus.

Fig. 1

PRISMA flow diagram of study selection

Fig. 2

Forest plots of the effects of SGLT2i on cardiac structure indexed by body surface area. a LVMI; b LVEDVI; c LVESVI; d LAVI. SGLT2i sodium–glucose cotransporter 2 inhibitors, T2DM type 2 diabetes mellitus, HF heart failure, LVMI left ventricular mass indexed by body surface area, LVEDVI left ventricular end diastolic volume indexed by body surface area, LVESVI left ventricular end systolic volume indexed by body surface area, LAVI left atrial volume indexed by body surface area

Fig. 3

Forest plots of the effects of SGLT2i on cardiac function. a LVEF; b GLS; c E/eʹ. SGLT2i sodium–glucose cotransporter 2 inhibitors, T2DM type 2 diabetes mellitus, HF heart failure, LVEF left ventricular ejection fraction, GLS global longitudinal strain, E/eʹ mitral inflow to mitral relaxation velocity ratio

Fig. 4

Forest plots of the effects of SGLT2i on a NT-proBNP and b KCCQ score. SGLT2i sodium–glucose cotransporter 2 inhibitors, T2DM type 2 diabetes mellitus, HF heart failure, NT-proBNP N-terminal pro-brain natriuretic peptide, KCCQ the Kansas City Cardiomyopathy Questionnaire