Abstract
BackgroundAlthough 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.MethodsWe 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.ResultsCompared 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.ConclusionThe 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.
Highlights
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
Participants with T2DM that were mostly in stage A–B HF were enrolled in studies [24, 25, 39, 40, 44, 46, 48, 49, 51, 52], and patients with T2DM and stage C HF were enrolled in studies [10, 29–31, 33, 41–43, 45, 47, 50]
In subgroup analyses in stage C HF patients based on HF types, SGLT2i was related to improved left ventricular ejection fraction (LVEF) in heart failure with reduced ejection fraction (HFrEF) patients (MD 3.16%, 95% confidence interval (CI) 0.11 to 6.22, p = 0.04; I2 = 0%), but was insignificant in heart failure with preserved ejection fraction (HFpEF) patients (MD 0.19%, 95% CI − 1.76 to 2.15, p = 0.85; I2 = 0%) (Additional file 4: Figure S3)
Summary
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. T2DM increases the risk of coronary heart disease and subsequent HF, especially HFrEF [2] Both in HFrEF and HFpEF patients, comorbid T2DM is associated with a worse prognosis [3–5]. SGLT2i was recommended by the latest guidelines of the American Diabetes Association and the European Association for the Study of Diabetes in patients with T2DM and HF [13], and several agents were recommended by the Heart Failure Association of the European Society of Cardiology in T2DM patients at high cardiovascular risk or with established cardiovascular disease, especially symptomatic HFrEF [14]. The mechanism and intermediate links of the drugs remain to be clarified
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