Background: Treating HFpEF (heart failure with preserved ejection fraction) is complex due to its diverse origins, leaving many patients with limited options. While diuretics offer symptom relief, most therapies don’t markedly improve outcomes. SGLT2 inhibitors, particularly Dapagliflozin, show potential in reducing cardiovascular events. Yet, guidelines for HFpEF and HFmrEF are vague regarding SGLT2 use. This meta-analysis aims to clarify the impact of SGLT2 inhibitors by analyzing relevant clinical RCTs.

Methods: In compliance with Cochrane and PRISMA criteria, this meta-analysis was performed. A comprehensive literature search encompassing databases like CENTRAL, Google Scholar, PubMed, CINAHL, Scopus, and Web of Science up to 2022 utilized keywords focused on SGLT2 inhibitors and heart failure. The PICOS framework helped define eligibility criteria, emphasizing patients with heart failure and the efficacy and safety of SGLT2 inhibitors in inpatient settings. Post systematic search, articles were screened, duplicates removed, and final selections made through consensus among reviewers. Relevant data were extracted using a standardized form, with quality assessment done via the Cochrane Risk of Bias tool. For synthesis, the Cochrane Review Manager Software was employed, adopting a random-effects model. Forest plots visualized the combined measurements, while heterogeneity and sensitivity analyses ensured accurate findings.

Results: In our meta-analysis of 15 studies, SGLT2 inhibitors were found to significantly reduce the rates of heart failure hospitalization and cardiovascular death in patients with HFpEF and HFmrEF. However, these inhibitors did not completely eliminate the risk of individual cardiovascular or total deaths. Their benefits primarily arise from reduced hospitalizations due to heart failure. A subgroup analysis highlighted their greater effectiveness in patients with reduced ejection fraction (HFrEF: OR 0.73, CI 95% 0.69-0.77, p< 0.00001) compared to those with preserved ejection fraction (HFpEF: OR 0.99, CI 95% 0.87-1.12, p=0.83). Our study does recognize several limitations, such as inconsistent baseline data .We recommend more expansive studies for clearer conclusions and encourage future research to delve deeper into this relationship.

Conclusions: Based on our meta-analysis, SGLT2 inhibitors notably reduce the combined risk of cardiovascular death and heart failure hospitalization in patients with a left ventricular ejection fraction (LVEF) exceeding 40 %. These findings underscore the potential of SGLT2 inhibitors as a standard treatment for patients with heart failure, whether they have preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF). Irrespective of their past disease experience, our results suggest that all heart failure patients could benefit from SGLT2s.