Efficacy and safety of sodium-glucose cotransporter inhibitors in hypertrophic cardiomyopathy: a systematic review

• Current evidence on SGLTi in HCM is limited and mostly from diabetic patients; • Preliminary data suggest SGLTi may reduce mortality in mixed-metabolic HCM; • Benefit seems related to metabolic or mixed phenotypes, rather than sarcomeric HCM; • Data on heart failure hospitalizations and disease progression are inconsistent; • Safety outcomes appear similar to controls, with no excess adverse events. 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. 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. 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. 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.