Heart Failure Outcomes with SGLT2 Inhibitors in Adults with Type 2 Diabetes: A Systematic Review and Meta-Analysis

Abstract

Background and Objectives: Type 2 diabetes mellitus (T2DM) substantially increases the risk of heart failure (HF) and worsens its prognosis. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), initially developed for glycemic control, have shown important cardiovascular benefits. This systematic review and meta-analysis evaluated the effects of SGLT2i on HF hospitalizations, cardiovascular (CV) death, and renal outcomes, as well as their safety profile, in patients with T2DM and established HF. Materials and Methods: Following PRISMA 2020 guidelines, we systematically searched PubMed, the Cochrane Library, and Web of Science for randomized controlled trials (RCTs) comparing SGLT2i with placebo in adults with T2DM and HF. Data on HF hospitalizations, CV death, other clinical outcomes, and adverse events were extracted. Risk of bias was assessed using the Cochrane RoB2 tool, and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using RevMan 5.4.1. Results: Ten RCTs including more than 21,000 participants met the inclusion criteria. Most were large, international, double-blind trials with overall low risk of bias. SGLT2i reduced the composite of worsening HF or CV death by about 21% (pooled HR 0.79, 95% CI 0.69–0.89), mainly driven by a consistent reduction in HF hospitalizations across trials. Effects on CV death alone were directionally favorable but not uniformly significant. Furthermore, SGLT2i were associated with beneficial effects on cardiac function and patient-reported health status and showed consistent renoprotective effects. The safety profile was favorable, with a small increase in genital infections and no excess of hypoglycemia or other serious adverse events. Conclusions: In patients with T2DM and HF, SGLT2i meaningfully reduce HF events and provide additional renal benefits with good tolerability. Our findings consolidate and update the current evidence by focusing specifically on RCTs enrolling patients with both T2DM and established HF across the spectrum of ejection fraction, thereby reinforcing the role of SGLT2i as a key component of guideline-directed therapy in this high-risk population.