J Clin Endocrinol Metab. 2026 Oct 28:dgag439. doi: 10.1210/clinem/dgag439. Online ahead of print.
ABSTRACT
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) can occur in individuals who are not overweight or have obesity (normal-BMI MASLD), yet disease burden and management remain poorly characterized. We compared long-term outcomes and incretin-based therapy use between normal-BMI MASLD (nbMASLD) and overweight/obesity-associated MASLD (obMASLD) across racial and ethnic groups.
METHODS: We conducted a retrospective, observational study using the TriNetX United States Network. Adults diagnosed with MASLD or metabolic dysfunction-associated steatohepatitis (MASH) from 2005-2025 were classified using ethnicity-informed normal-BMI thresholds: <23 kg/m2 for Asian, <27 kg/m2 for Native Hawaiian and Pacific Islander, and <25 kg/m2 for White/others. Propensity-score matching balanced demographic and clinical covariates. Outcomes were assessed using Kaplan-Meier analyses and Cox proportional hazards models with obMASLD as the reference group.
RESULTS: Among 619,171 eligible patients, 51,940 matched pairs were identified. Nb-BMI MASLD was associated with higher all-cause mortality across grouped ethnic groups, with survival of 77.49% versus 83.93% in obMASLD (HR 1.735, CI 1.653-1.822). Ethnicity-specific risks included higher myocardial infarction risk in White and Black patients, higher stroke risk in White patients, higher ESRD risk in Black patients, and increased cancers (colorectal, pancreatic and multiple myeloma) among White patients. Incretin-based therapy (IBT) use was markedly lower in nbMASLD but was associated with improved survival.
CONCLUSIONS: Patients with nbMASLD demonstrated an increased mortality and ethnicity-specific clinical complications than obMASLD despite a more favorable metabolic profile. These findings demonstrate a potential treatment gap for nbMASLD patients and the shortcomings of BMI-based strategies to risk-stratify MASLD patients.
PMID:42947552 | DOI:10.1210/clinem/dgag439