---
type: source
title: "SEMALCO Trial: Semaglutide 2.4mg + CBT Reduces Heavy Drinking Days by 41% in AUD — Lancet 2026"
author: "The Lancet (SEMALCO trial team, Psychiatric Centre Copenhagen)"
url: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)00305-3/fulltext
date: 2026-04-01
domain: health
secondary_domains: []
format: research-article
status: unprocessed
priority: high
tags: [GLP-1, semaglutide, alcohol-use-disorder, AUD, behavioral-health, addiction-medicine, RCT, clinical-trial]
intake_tier: research-task
---

## Content

**Study:** Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial. Published in The Lancet (2026).

**Trial design:** SEMALCO — 26-week, single-center, randomized, double-blind, placebo-controlled trial at Mental Health Center Copenhagen. N=108 treatment-seeking patients with moderate-to-severe AUD + comorbid obesity (BMI ≥30 kg/m²). Both arms received standard CBT. Randomized 1:1 to semaglutide 2.4mg subcutaneous weekly vs. placebo (saline).

**Primary findings:**
- Semaglutide arm: 41.1% reduction in heavy drinking days from baseline (95% CI −48.7 to −33.5)
- Placebo arm: 26.4% reduction (−34.1 to −18.6)
- Treatment difference: −13.7 percentage points (−22.0 to −5.4; p=0.0015)
- Roughly 12 heavy drinking days per month reduced in semaglutide group vs 8 in placebo group (50% higher absolute reduction)

**Secondary outcomes:**
- Semaglutide did NOT significantly reduce average drinks/day or total drinking days
- DID significantly reduce drinks per drinking day and weekly alcohol craving
- Blood-alcohol biomarkers (objective data) confirmed self-reported findings
- Greater reductions in cigarettes/day in subgroup with concurrent cigarette use

**Clinical significance:**
- NNT = 4.3 for semaglutide
- NNT for all currently approved AUD medications = 7 or higher (naltrexone, acamprosate, disulfiram)
- This is the largest RCT of semaglutide for AUD to date (previous: 48-person, 9-week, non-treatment-seeking trial)

**Safety:** GI side effects (nausea, loss of appetite, constipation, vomiting) occurred significantly more frequently with semaglutide but were generally mild and transient.

**Limitations (Science Media Centre expert reactions):**
- Single-center design reduces generalizability
- AUD+obesity comorbidity requirement — cannot extrapolate to AUD without obesity
- Both arms received CBT — unclear if semaglutide monotherapy would work (no behavioral support comparison arm)
- 26 weeks — no long-term durability data post-discontinuation
- Phase 3 trials underway but no timeline publicly announced

**Related trial (NCT05520775):** "Semaglutide for Alcohol Use Disorder" — separate trial
**Related trial (NCT07218354):** Listed in ClinicalTrials.gov as "Cessation or Reduction of..." — likely Phase 3 design, details limited

**FDA status (as of February 2026):** FDA has NOT approved GLP-1 drugs for addiction treatment.

## Agent Notes

**Why this matters:** This is the Phase 2 landmark for semaglutide in AUD. NNT 4.3 vs 7+ for approved medications is the most clinically significant AUD finding in a decade. If Phase 3 confirms, semaglutide would become first-line AUD pharmacotherapy. Market size: 14M+ US adults with AUD = potential $40-60B therapeutic category expansion for GLP-1 platform.

**What surprised me:** The biomarker confirmation (blood alcohol biomarkers supporting self-report) substantially strengthens the finding. Many behavioral trials rely entirely on self-report. The cigarette reduction secondary finding suggests GLP-1 may be acting across reward circuits simultaneously (not AUD-specific).

**What I expected but didn't find:** Clearer Phase 3 trial timelines. The NCT07218354 registration exists but design details weren't publicly accessible through search. No Novo Nordisk press release on AUD Phase 3 timeline was findable — unusual for a company that aggressively publicizes pipeline milestones.

**KB connections:**
- [[GLP-1 receptor agonists are the largest therapeutic category launch in pharmaceutical history but their chronic use model makes the net cost impact inflationary through 2035]] — this finding extends GLP-1 beyond metabolic disease
- the mental health supply gap is widening not closing because demand outpaces workforce growth — if GLP-1 treats AUD pharmacologically, it potentially bypasses the therapist workforce constraint
- medical care explains only 10-20 percent of health outcomes because behavioral social and genetic factors dominate — requires qualification for addiction medicine subpopulation

**Extraction hints:**
1. New claim: "Semaglutide demonstrates superior AUD efficacy to all approved medications (NNT 4.3 vs 7+) in RCT, extending GLP-1 therapeutic scope from metabolic to behavioral health"
2. Need Phase 3 timeline before making this claim's confidence above 'likely'
3. Critical scope qualification needed: AUD with comorbid obesity specifically — not general AUD population

**Context:** Published April 2026 (approximate), covered by MedicalXpress, PsychNews, multiple outlets. NIH press release April 2026. This is the SAME study referenced in Session 34 (NNT 4.3 finding). The Lancet publication is the primary source.

## Curator Notes (structured handoff for extractor)
PRIMARY CONNECTION: [[GLP-1 receptor agonists are the largest therapeutic category launch in pharmaceutical history but their chronic use model makes the net cost impact inflationary through 2035]]
WHY ARCHIVED: Foundational evidence for potential new claim about GLP-1 behavioral health expansion — the most significant AUD pharmacotherapy finding in years
EXTRACTION HINT: Write as a qualified new claim about GLP-1 AUD efficacy, with explicit scope (AUD+obesity, Phase 2 evidence, CBT co-intervention required). Flag for Phase 3 confirmation before confidence rises above 'likely'.
