A network meta-analysis of safety and efficacy of sodium-glucose cotransporter 2 inhibitors in heart failure patients

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown promise in treating heart failure (HF), but the best choice among these drugs remains unclear. This study aims to compare the effectiveness and safety of different SGLT2is in HF patients. Methods: We conducted a comprehensive search of 5 databases (PubMed, Scopus, Web of Science, Embase, and ClinicalTrials.gov) for randomized controlled trials (RCTs) conducted up until March 2023. These trials had to compare SGLT2i medications to a placebo in patients with HF. The main outcomes were all-cause mortality, cardiovascular mortality, hospitalization due to HF, and myocardial infarction (MI). Furthermore, we calculated the risk ratio (RR) with a 95% confidence interval (CI) using the random-effects model and inverse variance statistics. Results: We included 16 RCTs involving 80 666 patients (43 743 on SGLT2 inhibitors, 36 923 on placebo). No SGLT2 inhibitor demonstrated a significant difference in all-cause mortality and MI compared to others. However, empagliflozin significantly reduced the risk of cardiovascular mortality by 20% (RR: 0.80, 95% CI 0.69–0.93), including in patients with diabetes. All SGLT2 inhibitors lowered the risk of hospitalization for HF compared to placebo, except for canagliflozin. Sotagliflozin had the greatest reduction in hospitalizations (RR: 0.66, 95% CI 0.57–0.76), followed by empagliflozin (RR 0.73, 95% CI 0.66–0.81). There were no significant differences among SGLT2 inhibitors for stroke or drug discontinuation due to side effects. Notably, empagliflozin had a 13% lower risk of serious adverse events (RR 0.87, 95% CI 0.76–0.99). Conclusion: Empagliflozin was associated with the lowest risk of both cardiovascular mortality and serious side effects. While all SGLT2 inhibitors reduced the likelihood of hospitalizations for HF, canagliflozin did not show a significant benefit in this area. There were no significant differences between the SGLT2 inhibitors in terms of all-cause mortality, MI, stroke, or side effects leading to treatment discontinuation.