# SEMALCO Trial

**Full name:** Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity

**Institution:** Mental Health Center Copenhagen, Psychiatric Centre Copenhagen

**Trial type:** Phase 2, randomized, double-blind, placebo-controlled

**Status:** Published April 2026 in The Lancet

## Design

- **Population:** N=108 treatment-seeking patients with moderate-to-severe AUD + comorbid obesity (BMI ≥30 kg/m²)
- **Duration:** 26 weeks
- **Intervention:** Semaglutide 2.4mg subcutaneous weekly vs. placebo (saline), randomized 1:1
- **Co-intervention:** Both arms received standard cognitive behavioral therapy (CBT)
- **Setting:** Single-center (Mental Health Center Copenhagen)

## Primary Outcome

**Heavy drinking days reduction:**
- Semaglutide: 41.1% reduction from baseline (95% CI −48.7 to −33.5)
- Placebo: 26.4% reduction (−34.1 to −18.6)
- Treatment difference: −13.7 percentage points (−22.0 to −5.4; p=0.0015)
- NNT = 4.3 (vs. NNT ≥7 for all FDA-approved AUD medications)

## Secondary Outcomes

- **No significant effect on:** Average drinks/day, total drinking days
- **Significant reductions in:** Drinks per drinking day, weekly alcohol craving
- **Objective validation:** Blood-alcohol biomarkers confirmed self-reported findings
- **Cross-substance effect:** Greater cigarette reduction in subgroup with concurrent tobacco use

## Safety

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

## Significance

- Largest RCT of semaglutide for AUD to date (previous: 48-person, 9-week, non-treatment-seeking trial)
- Superior efficacy to all currently approved AUD medications
- First Phase 2 evidence for GLP-1 receptor agonists in AUD with comorbid obesity

## Limitations

- 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
- 26 weeks — no long-term durability data post-discontinuation

## Related Trials

- NCT05520775: "Semaglutide for Alcohol Use Disorder" (separate trial)
- NCT07218354: Phase 3 design, details limited

## Timeline

- **2026-04-01** — Published in The Lancet
- **2026-04** — Covered by NIH press release, MedicalXpress, PsychNews, multiple outlets