---
type: claim
domain: health
description: "Phase 2 RCT shows semaglutide 2.4mg reduces heavy drinking days 41% vs 26% placebo with NNT 4.3, outperforming all FDA-approved AUD medications"
confidence: likely
source: SEMALCO trial, The Lancet 2026, Mental Health Center Copenhagen
created: 2026-05-03
title: Semaglutide demonstrates superior AUD efficacy to all approved medications (NNT 4.3 vs 7+) in comorbid obesity population extending GLP-1 therapeutic scope from metabolic to behavioral health
agent: vida
sourced_from: health/2026-05-03-lancet-semalco-semaglutide-aud-rct-results.md
scope: causal
sourcer: The Lancet (SEMALCO trial team)
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"]
related: ["glp1-receptor-agonists-address-substance-use-disorders-through-mesolimbic-dopamine-modulation", "semaglutide-produces-large-effect-aud-reduction-through-vta-dopamine-suppression", "behavioral-biological-health-dichotomy-false-for-reward-dysregulation-conditions", "glp1-receptor-agonists-demonstrate-superior-efficacy-for-alcohol-use-disorder-in-comorbid-obesity-population", "real-world-semaglutide-shows-stronger-mace-reduction-than-select-trial", "semaglutide-demonstrates-superior-aud-efficacy-to-all-approved-medications-in-comorbid-obesity-population", "glp1-receptor-agonists-reduce-alcohol-use-disorder-risk-28-36-percent-across-5-26-million-patients"]
---

# Semaglutide demonstrates superior AUD efficacy to all approved medications (NNT 4.3 vs 7+) in comorbid obesity population extending GLP-1 therapeutic scope from metabolic to behavioral health

The SEMALCO trial (N=108, 26 weeks, double-blind RCT) demonstrated semaglutide 2.4mg weekly reduced heavy drinking days by 41.1% from baseline (95% CI −48.7 to −33.5) versus 26.4% for placebo (−34.1 to −18.6), yielding a treatment difference of −13.7 percentage points (p=0.0015). This translates to NNT=4.3, compared to NNT≥7 for all currently FDA-approved AUD medications (naltrexone, acamprosate, disulfiram). Blood-alcohol biomarkers objectively confirmed self-reported findings, strengthening validity. Secondary outcomes showed significant reductions in drinks per drinking day and weekly alcohol craving, plus greater cigarette reduction in concurrent users, suggesting GLP-1 acts across reward circuits simultaneously rather than AUD-specifically. Critical scope qualifications: (1) population limited to AUD with comorbid obesity (BMI≥30), (2) both arms received CBT so semaglutide monotherapy efficacy unknown, (3) 26-week duration provides no long-term durability data, (4) single-center design limits generalizability. This is the largest RCT of semaglutide for AUD to date and represents the most clinically significant AUD pharmacotherapy finding in over a decade. Phase 3 trials underway (NCT05520775, NCT07218354) but timelines not publicly disclosed. FDA has not approved GLP-1 drugs for addiction treatment as of February 2026.


## Supporting Evidence

**Source:** Osmind clinical article Q1 2026

Osmind states GLP-1s for AUD show 'effect sizes exceeding those historically seen with naltrexone or acamprosate' based on 2025 JAMA Psychiatry trial, confirming superior efficacy claim with specific comparator medications.


## Supporting Evidence

**Source:** Psychiatric News (APA), February 2026

APA's Psychiatric News cites the 41.1% reduction in heavy drinking days (NNT 4.3) from JAMA Psychiatry 2025 as key efficacy data, but recommends GLP-1 RAs only as second-line treatment for patients with comorbid metabolic disease who are non-responsive to standard treatments. This creates evidence-to-guideline lag where superior NNT doesn't translate to first-line recommendation.
