Therapeutic efficacy and safety profile of SGLT-2 inhibitor dapagliflozin in heart failure with reduced and preserved ejection fraction: a systematic review and meta-analysis

Background: Heart failure (HF) stands as one of the world’s major causes of morbidity and mortality, yet there is insufficient therapeutic choice, particularly for patients with heart failure with preserved ejection fraction (HFpEF) and mildly reduced ejection fraction (HFmrEF). Patients treated with SGLT2 inhibitors experience cardiovascular benefits as an additional effect beyond its glucose control capabilities. In this meta-analysis, the effectiveness and safety of SGLT2 inhibitors are assessed for patients with heart failure with reduced ejection fraction (HFrEF), HFpEF, and HFmrEF. Of particular interest is their effect on cardiovascular mortality, heart failure hospitalizations, and symptom burden. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. Research performed on the Cochrane Library, PubMed, and Embase electronic databases retrieved randomized controlled trials (RCTs) and cohort studies that evaluated SGLT2 inhibitors treatment for patients with reduced (HFrEF), preserved (HFpEF), and mid-range (HFmrEF) ejection fraction levels. The study analyzed cardiovascular mortality together with heart failure hospitalizations and symptom improvement as well as renal function decline among heart failure patients. The analysis incorporated Hazard ratios (HRs) and 95% confidence intervals (CIs) using a random-effects model to pool the data. The assessment of heterogeneity used Cochran’s Q test alongside the I 2 statistic, and publication bias was evaluated through funnel plots and Egger’s regression test. Results: The examined research included eight studies that utilized clinical trials combined with real-world data for analysis. Both patients with HFrEF (HR: 0.74, 95% CI: 0.65–0.85, P < 0.001) and HFpEF (HR: 0.82, 95% CI: 0.73–0.92, P = 0.0008) experienced significant decreases in cardiovascular death and HF progression through SGLT2 inhibitors treatment. Benefits in HFmrEF patients were similar to those in HFpEF, mainly based on subgroup analyses in the DELIVER trial. Patients treated with SGLT2 inhibitors experienced a 24% reduction in hospital admissions compared to a control group with rates confirmed through an analysis of HR: 0.76 (95% CI: 0.63–0.93, P = 0.01). Patients taking SGLT2 inhibitors showed a 39% decrease in kidney failure risk according to analysis (HR: 0.61, 95% CI: 0.51–0.72, P < 0.001). The treatment showed positive effects on symptoms through early NT-proBNP reduction and improved self-reported patient outcomes. The assessment of heterogeneity showed moderate levels through I 2  = 52.7% while detecting no meaningful publication bias. Conclusion: With their ability to improve symptoms and lower cardiovascular mortality, hospitalizations, and renal decline, SGLT2 inhibitors offer substantial clinical benefits for all three types of heart failure: HFrEF, HFmrEF, and HFpEF. These results lend credence to their incorporation into medical therapy for heart failure that is guided by guidelines, irrespective of diabetes or ejection fraction.