Semaglutide in Heart Failure With Preserved Ejection Fraction: Emerging Evidence and Clinical Implications

Area of Science:

• Cardiology
• Endocrinology
• Pharmacology

Background:

• Heart failure with preserved ejection fraction (HFpEF) is a growing public health concern with limited treatment options.
• Obesity and type 2 diabetes (T2D) are common comorbidities in HFpEF, complicating management.
• Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) like semaglutide show potential for treating these comorbidities.

Purpose of the Study:

• To analyze the efficacy and safety of semaglutide in patients with HFpEF, particularly those with obesity and T2D.
• To evaluate semaglutide's impact on HFpEF symptoms, functional status, and relevant biomarkers.
• To assess semaglutide's cardiovascular safety and compare its effects with existing therapies.

Main Methods:

• Systematic analysis of key clinical trials including STEP HFpEF, STEP HFpEF DM, SUSTAIN 6, and PIONEER 6.
• Inclusion of supportive studies on GLP-1 RAs and sodium-glucose cotransporter 2 (SGLT2) inhibitors.
• Review of mechanistic insights into semaglutide's metabolic, anti-inflammatory, and decongestive effects.

Main Results:

• Semaglutide significantly improved Kansas City Cardiomyopathy Questionnaire scores, reduced weight, and decreased C-reactive protein levels in obese HFpEF patients.
• Trials in T2D populations demonstrated cardiovascular safety, reducing stroke and mortality risks.
• Combination therapy with SGLT2 inhibitors showed a reduction in HF exacerbations.

Conclusions:

• Semaglutide offers a promising therapeutic option for obese patients with HFpEF, enhancing symptoms, function, and quality of life.
• Findings are primarily based on trials with specific inclusion criteria (obesity, preserved renal/cardiac function), limiting generalizability.
• Further long-term trials, cost-effectiveness studies, and comparative analyses are essential to define semaglutide's role across diverse HFpEF phenotypes.