Abstract
BACKGROUND: Sodium-Glucose Cotransporter inhibitors (SGLTi) are established therapies for heart failure (HF), chronic kidney disease, and type 2 diabetes. Their role in hypertrophic cardiomyopathy (HCM) remains undefined. This systematic review synthesizes available evidence on SGLTi efficacy and safety in HCM. METHODS: We systematically searched PubMed, Embase, and Cochrane to 2 June 2025 for studies reporting cardiovascular outcomes or safety adverse events in HCM patients treated with SGLTi. RESULTS: Three studies were included, comprising 5046 HCM patients, of whom 2523 (50%) received SGLTi. The population was predominantly male (68.9%), mean age 63.4 (±12.7), with high diabetes prevalence (90.6%). Cohorts were heterogeneous: one included 41.6% obstructive HCM, one only non-obstructive HCM, and one unspecified obstruction. Follow-up ranged 6-37.2 months. The high prevalence of diabetes and hypertension, along with limited genetic data, suggest some patients may have metabolic-mixed phenotypes rather than classic sarcomeric HCM.Two studies, (n = 4998, 90.5% diabetics) reported an association between SGLTi and reduced all-cause mortality. HF hospitalizations results were inconsistent: one study (n = 4126, 100% diabetics) showed reduction, while two other (respectively n = 48, 100% diabetics, and n = 872, 45.5% diabetics) resulted neutral. Two studies (n = 920) reported comparable adverse events. CONCLUSION: Evidence on SGLTi in HCM is limited, largely observational, and confined to diabetic-metabolic patients. Observed reduction in all-cause mortality likely reflects these metabolic or mixed phenotypes rather than classical sarcomeric HCM. Effects on HF hospitalizations remain uncertain. No safety concerns emerged. These findings are hypothesis-generating and highlight need for randomized controlled trials of SGLTi in HCM with or without diabetes.