Dapagliflozin reduced heart failure hospitalization or cardiovascular death by 26% (HR 0.74, 95% CI 0.65-0.85) in patients with HFrEF; similar reductions observed with empagliflozin and canagliflozin in HF and CKD populations.
Do SGLT2 inhibitors improve clinical outcomes in patients with heart failure, chronic kidney disease, and nonalcoholic fatty liver disease?
SGLT2 inhibitors are foundational, guideline-directed therapies that provide multifaceted protection across the cardiorenal-metabolic spectrum, though their role in hepatic disease requires further long-term outcome trials.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors were first introduced to enhance glycemic control in type 2 diabetes mellitus (T2DM). However, a series of large-scale cardiovascular and renal outcomes trials have revealed their substantial benefits in reducing heart failure (HF) hospitalizations, slowing chronic kidney disease (CKD) progression, and improving cardiorenal outcomes, even among non-diabetic populations. Early studies further suggest potential benefits in non-alcoholic fatty liver disease (NAFLD). In this comprehensive review, we synthesize the mechanistic basis, landmark trials, real-world evidence, and emerging guidelines that position SGLT2 inhibitors as cornerstone therapies in the management of HF and CKD, with growing research in NAFLD. By highlighting key clinical outcomes, safety profiles, and cost-effectiveness considerations, we underscore how SGLT2 inhibitors transcend their original role in glucose regulation to provide multifaceted protection across the cardiorenal-metabolic spectrum.
Sosa et al. (Mon,) conducted a review in Patients with heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), chronic kidney disease (CKD) with and without type 2 diabetes, and patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). SGLT2 inhibitors (including dapagliflozin, empagliflozin, canagliflozin) vs. Placebo was evaluated on Composite endpoint of heart failure hospitalization or cardiovascular death for heart failure trials; composite of CKD progression or cardiovascular death for CKD trials; liver fat fraction and histological improvement for NAFLD trials. Dapagliflozin reduced heart failure hospitalization or cardiovascular death by 26% (HR 0.74, 95% CI 0.65-0.85) in patients with HFrEF; similar reductions observed with empagliflozin and canagliflozin in HF and CKD populations.