GLP-1 Receptor Agonists in Heart Failure Management
GLP-1 receptor agonists should be used with caution in patients with heart failure with reduced ejection fraction (HFrEF), as they have shown no clear benefit and potential safety concerns in this population, while they may have theoretical benefits in heart failure with preserved ejection fraction (HFpEF).
Current Evidence on GLP-1 RAs in Heart Failure
Heart Failure with Reduced Ejection Fraction (HFrEF)
- Clinical trials examining GLP-1 RAs in HFrEF have shown neutral or potentially concerning results:
- The LIVE trial found that liraglutide did not improve left ventricular ejection fraction compared to placebo in stable chronic heart failure patients 1
- Patients in the liraglutide group had a numerically increased risk for the composite outcome of death and HF hospitalization (HR 1.30; 95% CI 0.92-1.83) 2
- More concerning, the LIVE trial showed significantly more serious cardiac events in patients treated with liraglutide (10%) compared to placebo (3%) (p=0.04) 1
- Liraglutide was also associated with increased heart rate (mean difference: 7 bpm) 1
Heart Failure with Preserved Ejection Fraction (HFpEF)
- Recent evidence suggests potential benefits in HFpEF patients:
Recommendations Based on Heart Failure Phenotype
For Patients with HFrEF:
- Exercise caution when using GLP-1 RAs in patients with HFrEF
- Consider alternative glucose-lowering therapies, particularly SGLT2 inhibitors, which have demonstrated clear benefits in HFrEF 2
- If GLP-1 RA therapy is necessary for glycemic control:
- Monitor for signs of worsening heart failure
- Watch for increased heart rate
- Be vigilant for cardiac adverse events
For Patients with HFpEF:
- GLP-1 RAs may be considered, especially in patients with:
- Obesity
- Type 2 diabetes
- Need for weight reduction
- Semaglutide has shown improvements in heart failure symptoms and physical limitations in this population 3
Cardiovascular Risk Reduction
- Both liraglutide and semaglutide are FDA-approved to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease 4, 5
- This benefit appears to be primarily in preventing atherosclerotic events rather than heart failure outcomes 2
- The American Diabetes Association and European Association for the Study of Diabetes recommend GLP-1 RAs for cardiovascular risk reduction independent of baseline HbA1c 2
Clinical Considerations and Monitoring
Before initiating GLP-1 RAs:
- Screen for heart failure with directed clinical history, physical examination, echocardiogram, and natriuretic peptide measurement 6
- Determine heart failure phenotype (HFrEF vs. HFpEF) as this will guide decision-making
- Evaluate for contraindications including personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 6, 4
During treatment:
- Monitor renal function, especially when initiating or escalating doses 6
- Watch for gastrointestinal side effects, which are common with GLP-1 RAs
- Be alert for symptoms of worsening heart failure, particularly in HFrEF patients
Important Caveats
- The Heart Failure Society of America consensus statement advises caution with GLP-1 RAs in individuals with acute heart failure decompensation 2
- SGLT2 inhibitors are preferred over GLP-1 RAs when heart failure or chronic kidney disease predominates 2
- The distinction between using GLP-1 RAs for prevention versus treatment of heart failure is crucial - they may be appropriate for patients at risk of heart failure but have uncertain benefit or potential harm in established HFrEF 2