---
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.


## Challenging Evidence

**Source:** PMC systematic review + JAMA Psychiatry RCT

Large community-based cohort study found 195% increased risk of major depressive disorder among individuals treated with liraglutide or semaglutide. While the AUD RCT (N=108) showed 41.1% reduction in heavy drinking days with NNT 4.3 and no psychiatric adverse events, the observational cohort data suggests psychiatric monitoring infrastructure is required for behavioral health deployment. The mechanistic hypothesis is that GLP-1 reduces reward salience (beneficial for addiction) but may reduce hedonic response broadly (potential depression pathway). This creates a clinical tension: the drug is extraordinarily effective for AUD but may carry psychiatric risk requiring screening and monitoring protocols.
