OBJECTIVES: Sodium–glucose cotransporter-2 inhibitors (SGLT-2i) have a positive impact on reducing cardiovascular mortality and heart failure (HF) hospitalizations. This systematic review and meta-analysis, evaluates the incremental net benefit (INB) of SGLT-2i treatment in HF patients.

METHODS: We searched five databases from inception to April 30, 2024, for economic evaluations of SGLT-2i in HF patients. Studies included analyzed the cost-effectiveness and cost-utility of SGLT-2i combined with standard triple-therapy versus standard triple-therapy alone. We systematically extracted study details, interventions, economic models, and outcomes, and assessed bias with the ECOBIAS checklist. INBs were calculated in 2022 USD, adjusted for purchasing power parity. Studies were stratified by perspective, with subgroup analyses by country income, SGLT-2i type, and ejection fraction. A random-effects model was used if heterogeneity was detected; otherwise, a fixed-effect model was applied. Heterogeneity was assessed via the Q test and I² statistic.

RESULTS: 41 studies with 55 comparisons were pooled into meta-analysis, with 35 from healthcare system perspective, and 20 from payer perspective. From the healthcare system perspective, adding SGLT-2i was cost-effective, with an INB of $4042.08 (95% CI: $1758.70-$6325.46). From the payer perspective, the INB was $12972.84 ($4711.5-$21234.22). Subgroup analyses mostly supported cost-effectiveness, yet SGLT-2i was not cost-effective in HF patients with preserved ejection fraction (HFpEF), showing INBs of $-639.32 ($-1850.09-$571.44) and $3611.07 ($-208.49-$7430.64) from healthcare and payer perspectives, respectively. Similarly, HF patients in lower/middle-income countries exhibited no significant cost-effectiveness from the payer perspective (INB, $55645.70; $-51000.00-$160000.00).

CONCLUSIONS: SGLT-2i addition to standard triple-therapy is cost-effective from both healthcare and payer perspectives. However, cost-effectiveness is less evident in HFpEF patients and those in low/middle-income countries. Further investigation, incorporating a broader societal perspective, is warranted to enhance understanding.