Sodium-glucose cotransporter 2 inhibitors for wild-type transthyretin amyloidosis: Insights from a global database

Wild-type transthyretin amyloidosis (wtATTR) is an increasingly recognised cause of infiltrative cardiomyopathy, particularly in the elderly population. The use of traditional heart failure prognostic therapies in this group may be limited by age-associated comorbidities and heightened vulnerability to changes in renal function and blood pressure. We aimed to assess the potential prognostic impact of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in wtATTR.

Using data from a federated global electronic medical record database (TriNetX), patients diagnosed with wtATTR between 2005 and 2025 were identified and followed for up to 5 years. Patients were stratified into two groups based on SGLT2i use with 1:1 propensity score matching (PSM) between the cohorts. The primary outcome was all-cause mortality, and secondary outcome was clinical decompensation for heart failure.

A total of 1,160 patients treated with SGLT2i and 2,325 patients without SGLT2i met inclusion criteria for the study. After PSM, each group contained 909 patients with comparable covariates. Mean age was 77.3±9.2 years (81.4% male) in the treatment group and 77.9±7.5 years (82.5% male) for control. Median follow-up was 297 days in the treatment group and 438 days in the control group. Patients treated with SGLT2i had lower all-cause mortality (hazard ratio [HR] 0.62; 95% CI 0.49-0.79) and clinical decompensation for heart failure (odds ratio [OR] 0.61; 95% CI 0.40-0.94).

SGLT2i use was associated with better survival and a lower incidence of clinical heart failure. These findings signal a potential prognostic benefit of SGLT2i in wtATTR that should be explored further.