Glucosamine supplementation attenuates progression of metabolic dysfunction-associated steatotic liver disease and related comorbidities.

Background & Aims: This study examines the impact of glucosamine on the progression and outcomes of metabolic dysfunction-associated steatotic liver disease (MASLD), and metabolic dysfunction and alcohol-associated liver disease (MetALD) using a large scale cohort.

Methods: Present study utilized inverse probability of treatment weighting (IPTW) to adjust for confounders in this cohort study. Participants were classified based on glucosamine use, and primary and secondary outcomes included all-cause mortality, liver cirrhosis, cardiovascular disease, cerebrovascular disease, and chronic kidney disease (CKD) incidences. Cox proportional hazards models were used to assess hazard ratios and 95 % confidence intervals.

Results: We found that glucosamine significantly reduces all-cause mortality in MASLD and MetALD cohorts after IPTW adjustment (P < 0.001). Additionally, glucosamine use was associated with lower liver cirrhosis incidence in MASLD both before (P = 0.003) and after IPTW adjustment (P = 0.046). Glucosamine also decreased cardiovascular disease risk in MASLD (P < 0.001) and MetALD (P = 0.037) cohorts, though it showed no significant impact on cerebrovascular disease incidence. Furthermore, glucosamine use was associated with a significantly lower incidence of CKD in the MASLD cohort (P = 0.034) and the entire cohort (P = 0.030), but not in the No steatotic liver disease cohort or MetALD cohort.

Conclusion: The findings suggest that glucosamine could be a beneficial supplementary therapy for managing steatotic liver diseases, particularly for patients at high risk for cardiovascular and renal complications. Further clinical trials are required to validate these potential benefits.