What GLP-2 (Glucagon-like peptide-2) analogs are recommended in the treatment of heart failure?

GLP-2 Analogs in Heart Failure

No GLP-2 analogs are currently recommended for the treatment of heart failure, and they should be distinguished from GLP-1 receptor agonists, which have established cardiovascular benefits but varying effects in heart failure.

Clarification on GLP-2 vs. GLP-1

It's important to clarify that GLP-2 (Glucagon-like peptide-2) and GLP-1 (Glucagon-like peptide-1) are distinct hormones with different physiological roles:

• GLP-2 analogs (like teduglutide) are primarily used for intestinal disorders such as short bowel syndrome
• GLP-1 receptor agonists are used for diabetes management and have been extensively studied for cardiovascular outcomes

Current Evidence on GLP-1 Receptor Agonists in Heart Failure

The guidelines provide recommendations specifically for GLP-1 receptor agonists (not GLP-2) in heart failure:

Heart Failure with Reduced Ejection Fraction (HFrEF)

• GLP-1 receptor agonists should be used with caution in patients with HFrEF 1
• Avoid GLP-1 receptor agonists if there has been recent heart failure decompensation 1
• Some studies have raised concerns about potential harm in patients with established HFrEF 1

Heart Failure with Preserved Ejection Fraction (HFpEF)

• GLP-1 receptor agonists may be considered in patients with HFpEF, particularly those with obesity or diabetes 2
• Recent meta-analysis suggests GLP-1 receptor agonists may reduce worsening HF events in HFpEF 2

Recommendations Based on Current Guidelines

1. For patients with established heart failure:

   • SGLT2 inhibitors are the preferred agents for reducing heart failure hospitalizations and cardiovascular death in both HFrEF and HFpEF 1
   • GLP-1 receptor agonists should be used with caution, particularly in HFrEF 1

2. For patients with diabetes at risk for heart failure:

   • SGLT2 inhibitors are preferred for heart failure risk reduction 1
   • GLP-1 receptor agonists may be considered for their benefits on atherosclerotic cardiovascular disease but not specifically for heart failure prevention 1

Clinical Decision-Making Algorithm

1. Assess heart failure status:

   • If patient has HFrEF: Prioritize SGLT2 inhibitors; avoid or use GLP-1 RAs with caution
   • If patient has HFpEF: Consider SGLT2 inhibitors first; GLP-1 RAs may be considered as additional therapy

2. Consider comorbidities:

   • If patient has diabetes with established atherosclerotic cardiovascular disease: Both SGLT2 inhibitors and GLP-1 RAs provide benefits
   • If patient has diabetes with predominant heart failure risk: Prioritize SGLT2 inhibitors over GLP-1 RAs

Important Caveats

• There is a lack of specific data on GLP-2 analogs in heart failure management
• The cardiovascular effects of GLP-1 receptor agonists appear to be class-specific and may vary between agents
• Human GLP-1 RAs may have different effects than non-human GLP-1 RAs in heart failure patients 3
• Ongoing trials are needed to better define the role of GLP-1 receptor agonists across the spectrum of heart failure

In summary, while GLP-1 receptor agonists have established cardiovascular benefits, there are no specific recommendations for GLP-2 analogs in heart failure management, and treatment decisions should prioritize SGLT2 inhibitors for heart failure risk reduction.