When weight-loss drugs reduce drinking: glucagon-like peptide-1 receptor agonists as phenotype-enriched harm-reduction therapy for alcohol use disorder.

Editorial synthesizing evidence from randomized trials and observational studies

“This editorial examines whether current evidence supports their classification as broadly applicable addiction treatments or as phenotype-enriched therapies.”

Adults with alcohol use disorder (AUD), often with comorbid obesity or type 2 diabetes

“The strongest current rationale may be for patients with heavy episodic or loss-of-control drinking who also have obesity, type 2 diabetes, or substantial cardiometabolic risk.”

Varies by cited trial; one specific trial involved 108 adults

“Among 108 treatment-seeking adults with AUD and obesity who also received cognitive behavioral therapy, 26 weeks of semaglutide produced a 41.1% reduction in heavy-drinking days, 13.7 percentage points greater than that observed with placebo, alongside improvements in weight and cardiometabolic measures[4].”

Varies by cited trial; one specific trial lasted 26 weeks

“Among 108 treatment-seeking adults with AUD and obesity who also received cognitive behavioral therapy, 26 weeks of semaglutide produced a 41.1% reduction in heavy-drinking days, 13.7 percentage points greater than that observed with placebo, alongside improvements in weight and cardiometabolic measures[4].”

GLP-1 RAs show consistent reductions in heavy-drinking days, drinks per drinking day, and naturalistic craving, but less consistent effects on total consumption and cue-elicited craving

“Reductions have been most consistent in heavy-drinking days, drinks per drinking day, naturalistic craving, alcohol-related consequences, and the World Health Organization (WHO) risk drinking level, whereas effects on total alcohol consumption, drinking frequency, and laboratory cue-elicited craving have been less consistent.”

Durable abstinence, sustained benefit after discontinuation, and mortality benefits remain unestablished

“Durable abstinence, sustained benefit after treatment discontinuation, prevention of alcohol-related hospitalization in randomized trials, and mortality benefit remain unestablished.”

Obesity may enrich treatment response but is not established as a necessary biomarker or the sole mediator of alcohol reduction

“Obesity may enrich treatment response and provide an independent metabolic indication, but current evidence neither identifies it as a necessary response biomarker nor establishes that alcohol reduction is mediated by weight loss.”

Existing trials have limited sample sizes and follow-up durations, and lack data on durability after treatment discontinuation or weight regain

“Existing trials have limited sample sizes and follow-up durations, and were not designed to determine whether alcohol-related benefits persist after weight regain or treatment withdrawal.”