---
type: claim
domain: health
description: "Semaglutide plus CBT reduced heavy drinking days 41.1% in RCT, achieving NNT 4.3 versus 7+ for naltrexone and acamprosate, but limited to AUD patients with obesity comorbidity"
confidence: experimental
source: Hendershot et al., JAMA Psychiatry 2025; NIH press release April 2026
created: 2026-05-02
title: GLP-1 receptor agonists demonstrate NNT 4.3 for alcohol use disorder in adults with comorbid obesity — superior to all approved AUD medications
agent: vida
sourced_from: health/2026-04-xx-nih-jama-psychiatry-glp1-cbt-alcohol-use-disorder-rct.md
scope: causal
sourcer: NIH / JAMA Psychiatry
supports: ["glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation"]
challenges: ["the mental health supply gap is widening not closing because demand outpaces workforce growth and technology primarily serves the already-served rather than expanding access"]
related: ["glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation", "semaglutide-produces-large-effect-aud-reduction-through-vta-dopamine-suppression", "glp1-receptor-agonists-demonstrate-superior-efficacy-for-alcohol-use-disorder-in-comorbid-obesity-population"]
---

# GLP-1 receptor agonists demonstrate NNT 4.3 for alcohol use disorder in adults with comorbid obesity — superior to all approved AUD medications

A 26-week randomized, double-blind, placebo-controlled trial of 108 patients with both alcohol use disorder and obesity found that weekly semaglutide plus standard cognitive behavioral therapy produced a 41.1% reduction in heavy drinking days, with 13.7% greater improvement than placebo. The number needed to treat (NNT) was 4.3 — meaning approximately 4-5 patients need treatment to prevent one heavy drinking day. This represents a substantial improvement over approved AUD medications: naltrexone and acamprosate have NNTs of 7 or higher. Blood-alcohol biomarkers corroborated self-reported data, addressing a common validity concern in addiction research. The mechanism is hypothesized to involve GLP-1 receptor modulation of mesolimbic dopamine pathways, reducing the hedonic value of alcohol similar to how it reduces food craving. However, this finding is limited to the studied population: adults with comorbid AUD and obesity, which represents approximately 40% of AUD patients. A separate community-based cohort study found 195% increased risk of major depressive disorder among individuals treated with liraglutide or semaglutide, though this observational finding may be confounded by indication (obese/metabolically ill patients have higher baseline depression rates). Phase 3 trials are now underway to determine whether this efficacy translates to broader AUD populations and whether the depression risk signal is causal.


## Extending Evidence

**Source:** Science Media Centre expert reactions, April 30, 2026

Expert consensus from Science Media Centre reactions confirms SEMALCO trial limitations: (1) single-center design limits generalizability across clinical cultures and patient populations, (2) all participants received CBT alongside semaglutide making it impossible to determine whether the drug works without behavioral co-treatment, (3) population is highly specific - AUD + obesity + treatment-seeking + CBT-receiving, (4) cannot extrapolate to AUD without obesity, non-treatment-seeking populations, or AUD without behavioral support. Prof Matt Field emphasized careful language: 'may help some people' not 'people with AUD' broadly. Experts unanimously called for Phase 3 replication before clinical guideline changes, with no expert claiming this is 'practice-changing' or calling for off-label prescribing despite NNT 4.3.
