Systematic Review and Meta-Analysis of Metabolic Changes Linked to Sacubitril/Valsartan Therapy
Overview
This systematic review and meta-analysis evaluated metabolic alterations associated with sacubitril/valsartan therapy, focusing on glycemic control and lipid profiles. The analysis synthesized data from multiple studies to clarify the drug's broader metabolic effects in patients with cardiovascular and cardiometabolic conditions.
Background
Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is primarily approved for heart failure with reduced ejection fraction and has shown benefits in other heart failure subtypes. Beyond hemodynamic effects, its dual mechanism influences metabolic pathways by inhibiting neprilysin, which degrades peptides involved in glycemic control and lipid metabolism. Understanding its metabolic impact is crucial, especially in patients with comorbidities such as diabetes, obesity, and chronic kidney disease. This review aims to comprehensively assess changes in glycemic indices and lipid parameters during sacubitril/valsartan therapy.
Data Highlights
The meta-analysis pooled mean differences in metabolic indices including triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), fasting blood sugar (FBS), hemoglobin A1c (HbA1c), and insulin resistance markers from baseline to follow-up in patients treated with sacubitril/valsartan. Data were extracted from randomized controlled trials and cohort studies with rigorous quality assessment and statistical synthesis according to PRISMA guidelines.
Key Findings
Sacubitril/valsartan therapy was associated with significant improvements in glycemic control, evidenced by reductions in fasting blood sugar and HbA1c levels.
Modest but favorable changes in lipid profiles were observed, including increases in HDL cholesterol and reductions in triglycerides.
Low-density lipoprotein (LDL) and total cholesterol (TC) levels showed variable responses, with some studies reporting slight decreases or no significant change.
Insulin resistance markers improved in several cohorts, suggesting enhanced insulin sensitivity linked to neprilysin inhibition.
The metabolic benefits were consistent across diverse patient populations, including those with heart failure, hypertension, and chronic kidney disease.
Quality assessment indicated generally low risk of bias in included randomized controlled trials and moderate to high quality in cohort studies.
Clinical Implications
Clinicians should consider the metabolic benefits of sacubitril/valsartan when managing patients with heart failure and cardiometabolic comorbidities. The drug's positive effects on glycemic control and lipid metabolism may contribute to overall cardiovascular risk reduction. Monitoring metabolic parameters during therapy can help optimize patient outcomes and guide adjunctive treatment decisions.
Conclusion
Sacubitril/valsartan exerts favorable metabolic effects beyond its cardiovascular benefits, improving glycemic indices and lipid profiles in patients with cardiometabolic diseases. These findings support its broader therapeutic role and highlight the importance of metabolic monitoring during treatment.
References
1--Sacubitril/valsartan as a pivotal therapeutic option in cardiovascular conditions
2--Approval and benefits in heart failure with reduced ejection fraction
3,4--Expanded indications for heart failure with mildly reduced and preserved ejection fraction
5,6--Antihypertensive and renoprotective properties in hypertension and CKD
7--Mechanism of action affecting metabolic pathways
