Can GLP-1 (Glucagon-like peptide-1) receptor agonists, such as liraglutide (Victoza) or semaglutide (Ozempic), be used to treat left ventricular hypertrophy (LVH) in patients with type 2 diabetes?

GLP-1 Receptor Agonists for Left Ventricular Hypertrophy in Type 2 Diabetes

GLP-1 receptor agonists can be considered for patients with type 2 diabetes who have left ventricular hypertrophy (LVH) to reduce cardiovascular risk, with dulaglutide having the strongest evidence for this specific indication. 1

Mechanism and Evidence

GLP-1 receptor agonists have demonstrated several beneficial effects on the cardiovascular system:

• Recent evidence shows GLP-1 receptor agonists can improve left ventricular global longitudinal strain (LV GLS), an important measure of myocardial contractility, after 6 months of treatment 2
• Semaglutide has been shown to ameliorate pressure overload-induced cardiac hypertrophy in experimental models by improving cardiac mitophagy and suppressing NLRP3 inflammasome activation 3
• These agents provide cardiovascular benefits through both glycemic and non-glycemic mechanisms, including:
  • Direct effects on the myocardium
  • Improved endothelial function
  • Reduced inflammation
  • Favorable effects on lipid profiles and blood pressure 4, 5

Clinical Recommendations Based on Guidelines

The American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) specifically recommend:

• GLP-1 receptor agonists can be considered in patients with type 2 diabetes without established cardiovascular disease (CVD) but with indicators of high risk, including:

  • Age ≥55 years with coronary, carotid, or lower extremity artery stenosis >50%
  • Left ventricular hypertrophy
  • eGFR <60 mL min–1 [1.73 m]–2
  • Albuminuria 1

• Among available GLP-1 receptor agonists, dulaglutide has the strongest evidence for primary prevention of cardiovascular events in patients without established CVD but with risk factors like LVH 1

Important Considerations for LVH Patients

When using GLP-1 receptor agonists in patients with LVH:

1. Patient selection:

   • Screen for heart failure before initiating therapy
   • Perform directed clinical history, physical examination, echocardiogram, and natriuretic peptide measurement 6

2. Monitoring:

   • Follow renal function when initiating or escalating doses 6
   • Monitor for improvement in cardiac function parameters, particularly LV GLS 2

3. Caution in certain populations:

   • Be aware that small trials in patients with established heart failure with reduced ejection fraction (HFrEF) have shown neutral or potentially concerning signals 1
   • The LIVE trial showed more serious adverse cardiac events with liraglutide than placebo in HFrEF patients (10.0% vs 3.0%, p=0.04) 1
   • The FIGHT trial showed a numerically increased (though not statistically significant) risk for death and HF hospitalization with liraglutide 1

GLP-1 RA Selection and Dosing

Medication	Initial Dose	Maintenance Dose	CV Benefit Evidence
Dulaglutide	0.75 mg weekly	0.75-4.5 mg weekly	12% MACE reduction (REWIND trial)
Semaglutide	0.25 mg weekly	Up to 2.4 mg weekly	26% MACE reduction (SUSTAIN-6)
Liraglutide	0.6 mg daily	Up to 3.0 mg daily	13% MACE reduction (LEADER trial)

Practical Approach

1. For patients with type 2 diabetes and LVH without established CVD:

   • Consider dulaglutide as first choice based on REWIND trial data showing benefit in this population 1

2. For patients with type 2 diabetes, LVH, and established atherosclerotic CVD:

   • Any GLP-1 receptor agonist with proven CV benefit (dulaglutide, semaglutide, liraglutide) would be appropriate 1, 6

3. For patients with type 2 diabetes, LVH, and heart failure:

   • SGLT2 inhibitors are preferred over GLP-1 receptor agonists as first-line therapy 1
   • Consider GLP-1 receptor agonists as add-on therapy if SGLT2 inhibitors are contraindicated or not tolerated 1

Conclusion

GLP-1 receptor agonists, particularly dulaglutide, represent a promising therapeutic option for patients with type 2 diabetes and LVH, with evidence supporting their use for cardiovascular risk reduction in this population. Recent research suggests direct beneficial effects on cardiac structure and function, though more dedicated studies are needed to fully establish their role in LVH management.