SGLT2 Inhibitors Linked to Lower Mortality but Higher Cardiovascular Complications in Patients with Hypertrophic Cardiomyopathy and Type 2 Diabetes: AHJ, December 2025

A recent study found that Sodium-glucose co-transporter 2 (SGLT2) inhibitors use in hypertrophic cardiomyopathy (HCM) patients with type 2 diabetes was associated with significantly reduced all-cause mortality despite increased risk of cardiogenic shock and other cardiovascular complications. The authors advocated that this may be due to the reduced preload caused by the diuretic effect of SGLT2 inhibitors.

These findings were published in American Heart Journal in December 2025.

This complex cardiovascular risk profile warrants further investigation through prospective randomized controlled trials.

Study Background

Hypertrophic cardiomyopathy is a prevalent genetic cardiac disorder characterized by left ventricular hypertrophy, diastolic dysfunction, arrhythmia risk, and variable clinical trajectories. When combined with type 2 diabetes, the cardiometabolic burden intensifies, increasing susceptibility to heart failure, arrhythmias, sudden cardiac death, and hemodynamic instability. While SGLT2 inhibitors have demonstrated robust cardiovascular and renal benefits across multiple populations, including heart failure and chronic kidney disease, their safety and efficacy in individuals with HCM have remained poorly defined. Patients with structural abnormalities are often underrepresented in clinical trials, leaving clinicians with limited guidance on the use of these therapies within this subgroup.

This study provides a large-scale evaluation of SGLT2 inhibitor outcomes in HCM patients with diabetes, offering crucial insight into potential benefits and risks.

Study Overview

Researchers conducted a retrospective cohort study using the TriNetX Global Collaborative Network, incorporating data from 136 healthcare organizations worldwide. Adults aged 18 to 79 years with confirmed hypertrophic cardiomyopathy and type 2 diabetes were included based on standardized diagnostic criteria.

Patients were divided into two cohorts: those prescribed SGLT2 inhibitors and those who were not. After robust propensity score matching to ensure comparable baseline characteristics, each group consisted of 7,906 patients. Clinical outcomes were evaluated over a five-year follow-up period, allowing assessment of both mortality and cardiovascular complications in routine practice.

Key Findings

The study found a significant reduction in all-cause mortality among patients receiving SGLT2 inhibitors.

However, the analysis also revealed increased risks across several cardiovascular parameters. SGLT2 inhibitor users had a higher incidence of cardiogenic shock, ventricular tachycardia, atrial fibrillation, and acute kidney failure.

This dual risk-benefit pattern highlights a uniquely complex clinical profile for SGLT2 inhibitor use in HCM patients with diabetes—one that differs markedly from their largely protective role observed in other cardiac populations.

Until prospective randomized trials provide more clarity, clinicians should weigh the benefits of improved survival against the heightened acute cardiovascular risks. Collaborative care involving cardiology, endocrinology, and nephrology may help optimize outcomes and mitigate complications. This study signals that while SGLT2 inhibitors hold promise for improving long-term survival, their use in hypertrophic cardiomyopathy requires precision and caution.

Clinical Inference: Navigating a Complex Therapeutic Balance

For clinicians, these findings emphasize the need for careful patient selection and close monitoring when prescribing SGLT2 inhibitors to individuals with HCM and type 2 diabetes. The mortality benefit suggests meaningful long-term advantages, potentially related to improved metabolic health, reduced cardiac workload, and better fluid balance. However, the elevated risk of cardiogenic shock and arrhythmia underscores the importance of individualized risk assessment, especially in patients with obstructive physiology or fluctuating volume status.

Reference: Nwaezeapu KI, Ajenaghughrure G, Essien E, Agyekum A. SGLT2 Inhibitors in Patients with Hypertrophic Cardiomyopathy and Type 2 Diabetes: Mortality Benefit Despite Increased Cardiovascular Risk Profile. American Heart Journal. 2025 Dec 1;290:8-9.