GLP-1 Receptor Agonists Linked to Lower All-Cause Mortality in Hypertrophic Cardiomyopathy: AHJ, December 2025 Study Reveals New Cardiovascular Benefits

A recent study found that Glucagon-like peptide-1 (GLP-1) receptor agonist use in hypertrophic cardiomyopathy (HCM) patients with type 2 diabetes was associated with significantly reduced all-cause mortality and lower risk of cardiogenic shock compared to non-users. The authors advocate that the favorable risk-benefit profile of GLP-1 agonists in this patient population warrants further investigation through prospective randomized controlled trials.

The findings are published in December 2025 in American Heart Journal.

A New Therapeutic Signal in a High-Risk Cardiac Population

Hypertrophic cardiomyopathy is one of the most common inherited heart diseases and is associated with significant morbidity due to diastolic dysfunction, arrhythmias, heart failure, and sudden cardiac death. Patients who also have type 2 diabetes face an even more complex cardiovascular risk landscape, characterized by insulin resistance, endothelial dysfunction, and increased inflammatory burden.

GLP-1 receptor agonists are well known for reducing cardiovascular events in patients with obesity and diabetes. However, evidence regarding their impact in HCM has been sparse because patients with structural heart disease are often underrepresented in clinical trials. This study bridges an important evidence gap by examining long-term outcomes in HCM patients receiving GLP-1 therapy across a large, diverse healthcare network.

Study Overview

Researchers conducted a retrospective cohort study using the TriNetX Global Collaborative Network, which aggregates electronic health records from 129 healthcare organizations worldwide. Adults diagnosed with hypertrophic cardiomyopathy and type 2 diabetes were eligible for inclusion.

The study compared two groups: patients prescribed GLP-1 receptor agonists and those who never received GLP-1 therapy. Propensity score matching was used to create two balanced cohorts, each consisting of 8,293 patients, minimizing bias from demographic or clinical differences. Outcomes were evaluated over a five-year follow-up period.

Key Findings from the Study

• The analysis demonstrated patients treated with GLP-1 receptor agonists experienced a substantial reduction in all-cause mortality, with nearly a 40% lower risk of death compared with matched controls.
• GLP-1 therapy was also linked to a 30% lower risk of cardiogenic shock, a severe manifestation of cardiac decompensation that carries high short-term mortality.
• Clinically important arrhythmias such as ventricular tachycardia and atrial fibrillation, were also significantly less frequent in patients receiving GLP-1 receptor agonists.
• However, the study did not observe significant differences between groups in case of acute kidney failure.

Clinical Implications: A Promising Consideration for HCM Management in T2D

For clinicians managing patients with both hypertrophic cardiomyopathy and type 2 diabetes, this study suggests that GLP-1 receptor agonists may offer meaningful survival benefits beyond glucose control. The significant reduction in all-cause mortality and lower incidence of cardiogenic shock point to a potentially protective cardiometabolic effect in a population with few targeted therapeutic options.

These findings highlight GLP-1 RA therapy as a promising adjunct in HCM with T2D, warranting confirmation through prospective randomized trials.

Reference: Nwaezeapu KI, Ajenaghughrure G, Essien E, Agyekum A. GLP-1 Receptor Agonists in Hypertrophic Cardiomyopathy: Mortality Benefit with Complex Cardiovascular Risk Profile. American Heart Journal. 2025 Dec 1;290:7-8.

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