Polypharmacy Among Older Adults with Metabolic Dysfunction–Associated Steatotic Liver Disease

Background Multimorbidity and polypharmacy are common in older adults with cardiometabolic diseases, but their burden in metabolic dysfunction-associated steatotic liver disease (MASLD) is less understood. Objective To characterize multimorbidity and polypharmacy among older adults with MASLD. Design Retrospective cohort study. Participants Adults ≥ 65 years with transient elastography data in NHANES 2017–2020. Main Measures MASLD was defined as steatosis plus ≥ 1 metabolic risk factor; polypharmacy was ≥ 5 medications. Participants were stratified by age (65–69, 70–74, and ≥ 75 years). Survey-weighted analyses evaluated age and polypharmacy in MASLD and non-MASLD adults. Multivariable models adjusted for comorbidities. Key Results An estimated 42 million US adults ≥ 65 years were included, 39.8% had MASLD. The proportion of women with MASLD decreased with age (55.5 to 39.3%, p = 0.04). Diabetes, obesity, and cardiometabolic burden were higher in MASLD across all age groups ( p < 0.01). Polypharmacy was most common in MASLD adults ≥ 75 years (60.3%), exceeding younger MASLD adults (36.9%, p = 0.002) and non-MASLD peers (42.7%; p = 0.005). MASLD adults had higher antidiabetic but lower antihypertensive use ( p < 0.05). MASLD adults ≥ 75 years had over three times the odds of polypharmacy versus those 65–69 years (aOR 3.12, 95%CI 2.21–4.42). Conclusions Older adults with MASLD ≥ 75 years face a significant and independent burden of polypharmacy. This challenge is especially salient in MASLD, where aggressive management of cardiometabolic comorbidities is essential to preventing disease progression and non-liver mortality, yet the medications used may heighten geriatric vulnerabilities. Age-appropriate medication review, deprescribing, and goal concordant care are critical to navigating this tension in this high-risk population.