Treatment approaches for alcohol use disorder with metabolic dysfunction.

Alcohol use disorder (AUD) and alcohol excess contribute significantly to morbidity and mortality through their multisystem effects, particularly on liver health. When combined with metabolic dysfunction--defined as obesity, hypertension, type 2 diabetes, and dyslipidemia--alcohol consumption has additive and synergistic effects that are associated with liver disease progression and increased risk of cardiovascular, cancer-related, hepatic, and all-cause mortality. Despite growing recognition of these overlapping risk factors, there remains no universally accepted threshold for "safe" alcohol consumption, as individual vulnerability varies widely depending on genetic, metabolic, and environmental factors. Individuals with co-occurring AUD and metabolic dysfunction face unique clinical challenges, yet current treatment frameworks rarely address this intersection. Existing pharmacologic and behavioral therapies for AUD are limited in efficacy and uptake, and they are often not tailored to the metabolic risks that accompany heavy drinking. This comorbid population represents an underrecognized group with clinical complexity and unmet therapeutic needs. In this review, we synthesize current knowledge across hepatology, psychiatry, and addiction medicine to characterize the shared pathophysiology and comorbidities of co-occurring AUD and metabolic dysfunction. We examine mortality trends, highlight gaps in current treatment paradigms, and evaluate how emerging research and treatments for MASLD, MetALD, and ALD can inform more effective clinical care strategies. Our aim is to establish a more unified framework for understanding and treating individuals with co-occurring AUD and metabolic dysfunction.