# Once-weekly semaglutide versus placebo in patients with alcohol use disorder and

> **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637)
> **Publisher:** CED Clinic (https://cedclinic.com)
> **Canonical URL:** https://cedclinic.com/once-weekly-semaglutide-versus-placebo-in-patients-with-alcohol-use-disorder-and/
> **Published:** 2026-06-03T18:13:14-04:00 | **Last Modified / Clinically Audited:** 2026-09-28T10:53:36-04:00
> **Clinical Summary:** A recent study found semaglutide significantly reduced heavy drinking days in patients with alcohol use disorder and obesity.

---

## Semaglutide Cuts Heavy Drinking Days in Alcohol Use Disorder

GLP-1 Receptor Agonists
[Alcohol Use Disorder](https://cedclinic.com/cannabis-infused-drinks-may-help-people-cut-their-alcohol-intake-in-half/)
Obesity
[Addiction Medicine](https://cedclinic.com/cognitive-flexibility-alcohol-cocaine-misuse-effects/)
Randomized Controlled Trial
**What You’ll Learn**

- How once-weekly semaglutide 2.4 mg performed against placebo on heavy drinking days over 26 weeks in patients with comorbid obesity and alcohol use disorder

- Which secondary alcohol-related, biomarker, and metabolic outcomes changed with semaglutide treatment

- Where the evidence is genuinely strong, where it demands skepticism, and what the trial cannot claim

- What these findings mean for patients and clinicians considering GLP-1 receptor agonists in addiction contexts

TL;DR: In a 26-week, double-blind RCT of 108 treatment-seeking adults with alcohol use disorder and obesity, once-weekly semaglutide 2.4 mg reduced heavy drinking days by an additional 13.7 percentage points versus placebo (p=0.0015), with consistent improvements across multiple alcohol-related, biomarker, and metabolic secondary outcomes.

Study Type: Randomized, Double-Blind, Placebo-Controlled Trial

## Abstract

**Background:** Alcohol use disorder accounts for 5% of deaths worldwide annually, and there is an urgent need for new therapeutic interventions. Preclinical and initial human studies indicate that the GLP-1 receptor agonist semaglutide might reduce alcohol drinking. This study evaluated the efficacy of semaglutide once-weekly in treatment-seeking patients with alcohol use disorder and comorbid obesity.

**Methods:** In a 26-week, single-centre, randomised, double-blinded, placebo-controlled trial, treatment-seeking participants with moderate to severe alcohol use disorder and comorbid obesity were assigned (1:1) to receive once-weekly semaglutide (2.4 mg subcutaneously) or placebo (saline subcutaneously), in addition to standard cognitive behavioural therapy. The primary endpoint was a reduction in the number of heavy drinking days assessed after 26 weeks of intervention, analysed with an ANCOVA model. Analysis adhered to the intention-to-treat principle, and missing outcome data were addressed using multiple imputations. Safety was assessed in all treated patients.

**Findings:** From June 10, 2023, to Feb 4, 2025, 108 participants (53 women and 55 men) were enrolled, with 54 participants in each of the semaglutide and placebo treatment groups, and all were included in the data analysis. Overall, 88 participants (81%) completed the full intervention. Semaglutide was associated with a reduction in heavy drinking days (–41.1 percentage points from baseline, 95% CI –48.7 to –33.5) compared with placebo (–26.4, –34.1 to –18.6; estimated treatment difference –13.7 percentage points, –22.0 to –5.4; p=0.0015), and had substantial effects on multiple secondary alcohol-related and somatic outcomes. Adverse events were transient, generally mild to moderate gastrointestinal effects, and occurred more frequently in the semaglutide group.

**Interpretation:** Semaglutide showed robust therapeutic effects in treatment-seeking participants with obesity and alcohol use disorder. This trial supports previous preclinical and clinical findings suggesting GLP-1 receptor agonists as a potential novel treatment target for alcohol use disorder.

**Source:** Klausen MK, Justesen SK, Pedersen JN, et al. Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial. *Lancet.* 2026;407:1687–98.

**Trial Registration:** ClinicalTrials.gov NCT05895643

**Open Access:** CC BY 4.0

## Study at a Glance

Design
26-week, single-centre, randomised, double-blind, placebo-controlled RCT

Population
Treatment-seeking adults (age 18–70) with moderate-to-severe AUD (DSM-5) and comorbid obesity (BMI ≥30 kg/m²); minimum 6 heavy drinking days in 30 days

Sample size (n)
108 (54 semaglutide, 54 placebo); 88 (81%) completed

Intervention
Semaglutide 2.4 mg SC once-weekly (dose-escalated from 0.25 mg) + CBT

Comparator
Saline placebo SC once-weekly + CBT

Primary Endpoint
Change in percentage of heavy drinking days from baseline to week 26 (TLFB method)

Key Finding
Semaglutide reduced heavy drinking days by 13.7 percentage points more than placebo (95% CI –22.0 to –5.4; p=0.0015)

## Study Snapshot

Outcome
Semaglutide
Placebo
Treatment Difference (95% CI)
p value

Heavy drinking days (% pts)
–41.1
–26.4
–13.7 (–22.0 to –5.4)
0.0015

Total alcohol (g/30 days)
–1550.2
–1025.9
–467.5 (–739.5 to –195.4)
<0.0009

Drinks per drinking day
–3.5 units
–2.1 units
–1.5 (–2.6 to –0.5)
0.0051

Alcohol craving (PACS score)
–9.2
–6.1
–3.1 (–5.1 to –1.2)
0.0020

Bodyweight (kg)
–11.2
–2.2
–9.0 (–11.2 to –6.7)
<0.0001

GGT (U/L)
–36.0
–10.2
–24.2 (–33.4 to –15.1)
<0.0001

Phosphatidyl ethanol (µmol/L)
–0.24
0.00
–0.28 (–0.41 to –0.15)
<0.0001

## Study Facts Table

Authors
Klausen MK, Justesen SK, Pedersen JN, Rasmussen L, Jensen A, Jensen ME, Knorr UB, Bergmann ML, Holst JJ, Hartmann B, Koob GF, Benveniste H, Volkow ND, Ekstrøm CT, Knudsen GM, Vilsbøll T, Fink-Jensen A

Journal / Year
*The Lancet,* 2026; 407:1687–98

Design
Single-centre, randomised, double-blind, placebo-controlled trial; 26 weeks

Total n
108 (54 per group); ITT analysis; 88 (81%) completed

Intervention
Semaglutide 2.4 mg SC once-weekly (dose-escalated per label) + up to 10 CBT sessions

Comparator
Saline placebo SC once-weekly (matched volume, needle size) + CBT

Primary Endpoint
Change in percentage of heavy drinking days from baseline to week 26 (TLFB)

Key Primary Result
ETD –13.7 percentage points (95% CI –22.0 to –5.4; p=0.0015) favoring semaglutide

Cohen’s d (heavy drinking days)
0.57 (95% CI 0.14–0.99)

NNT (2-level WHO risk level decrease)
4.3 (95% CI 2.33–30.3)

Adverse Events
Predominantly GI (nausea 57% vs 7%; constipation 35% vs 17%); mostly transient, mild-moderate; 4 semaglutide and 1 placebo participant discontinued due to side effects; 1 SAE per group (abdominal pain requiring hospital admission in semaglutide group at 0.25 mg dose)

Funding
Research Foundation Mental Health Services (Capital Region of Denmark), Novo Nordisk Foundation, Novavi Foundation, Hartmann Foundation, Augustinus Foundation

Conflict of Interest
Principal investigator (AF-J) received an unrestricted Novo Nordisk grant for a separate study; serves on a Novo Nordisk RCT advisory panel (no honorarium). Lead author (MKK) consulted for Pharmacotherapies for AUD Alliance and Guidepoint. TV has extensive advisory/speaker relationships with multiple pharmaceutical companies. Manufacturer had no role in design, data collection, analysis, interpretation, or writing.

## What Researchers Actually Did

From June 2023 to February 2025, investigators at Mental Health Centre Copenhagen enrolled 108 adults with DSM-5 moderate-to-severe alcohol use disorder, a BMI of 30 kg/m² or higher, an AUDIT score above 15, and a minimum of 6 heavy drinking days (defined as at least 60 g of alcohol per day for men and at least 48 g per day for women) within the 30 days prior to enrolment. Participants were randomised 1:1 to once-weekly subcutaneous semaglutide, escalated every 4 weeks from 0.25 mg to a target of 2.4 mg, or to matched saline placebo injections. All participants received up to 10 sessions of standardised CBT focused on motivation, craving management, and relapse prevention. Participants wore blindfolds and headphones during weekly injection visits to mask the audible pen-click from the semaglutide device. CBT delivery and all outcome assessments were conducted by masked personnel; statistical analyses were performed by a masked external statistician.

The primary outcome was the change in the percentage of heavy drinking days, measured using the Timeline Followback (TLFB) method. To address the known phenomenon of reduced drinking after initial telephone screening, baseline alcohol use was anchored to the 30 consecutive days with the highest alcohol consumption drawn from the 40 days preceding enrolment. This same highest-consumption 30-day window was applied at every subsequent assessment, preserving internal consistency but departing from the conventional approach of using the most recent 30-day window. Analysis followed the intention-to-treat principle. Missing data were handled with multiple imputation by predictive mean matching, with three pre-planned sensitivity analyses under more conservative assumptions.

## Key Findings: Primary Outcomes

- **Heavy drinking days (primary endpoint):** Semaglutide reduced heavy drinking days by 41.1 percentage points from baseline (95% CI –48.7 to –33.5), versus 26.4 percentage points with placebo (–34.1 to –18.6). The estimated treatment difference was –13.7 percentage points (95% CI –22.0 to –5.4; p=0.0015).

- **Effect size:** Cohen’s d=0.57 (95% CI 0.14–0.99) for heavy drinking days — within the medium range by convention.

- **Sensitivity analyses:** Complete-case analysis, return-to-baseline imputation, and 50% reduction imputation all preserved the direction and approximate magnitude of the primary finding, as reported by the authors.

- **Post-hoc adjustment for sex, age, and baseline heavy drinking days:** Results remained robust (reported in appendix).

## Key Findings: Secondary Outcomes and Subgroup Analyses

- **Total alcohol consumption:** –1550.2 g/30 days (semaglutide) vs –1025.9 g/30 days (placebo); ETD –467.5 g/30 days (95% CI –739.5 to –195.4; p<0.0009). Cohen’s d=0.54.

- **Drinks per drinking day:** –3.5 units vs –2.1 units; ETD –1.5 (–2.6 to –0.5; p=0.0051). Cohen’s d=0.45.

- **Alcohol craving (PACS score):** ETD –3.1 (–5.1 to –1.2; p=0.0020).

- **AUDIT score:** ETD –3.3 (–5.5 to –1.1; p=0.0044).

- **AUDIT-C score:** ETD –1.5 (–2.6 to –0.4; p=0.0071).

- **WHO risk drinking levels:** ETD –0.52 (–0.89 to –0.16; p=0.0055). Semaglutide participants also showed a significantly greater 2-level reduction in WHO risk drinking category versus placebo.

- **Number needed to treat** for a 2-level WHO risk level decrease: 4.3 (95% CI 2.33–30.3).

- **Days without alcohol consumption:** ETD 10.1 percentage points (–0.0 to 20.2; p=0.051) — this secondary endpoint did not reach statistical significance.

- **Phosphatidyl ethanol (objective alcohol biomarker):** ETD –0.28 µmol/L (–0.41 to –0.15; p<0.0001), corroborating self-reported outcomes.

- **GGT (liver enzyme):** ETD –24.2 U/L (–33.4 to –15.1; p<0.0001).

- **Mean corpuscular volume:** ETD –1.7 fL (–2.6 to –0.7; p=0.0007).

- **Amylase:** Semaglutide group showed an increase of 4.7 U/L vs a decrease of 0.9 U/L with placebo; ETD 5.1 (2.5–7.7; p=0.0002). Four semaglutide participants had asymptomatic amylase elevations above the upper limit of normal (highest: 123 U/L; normal range 10–65 U/L).

- **Bodyweight:** ETD –9.0 kg (–11.2 to –6.7; p<0.0001). Mean weight loss was –11.2 kg with semaglutide vs –2.2 kg with placebo.

- **Waist circumference:** ETD –8.3 cm (–11.2 to –5.4; p<0.0001).

- **HbA1c:** ETD –0.3% (–0.4 to –0.2; p<0.0001).

- **Systolic blood pressure:** ETD –6.8 mm Hg (–13.5 to –0.1; p=0.047).

- **[Quality of life](https://cedclinic.com/cannabis-policy-enforcement-february-26-2026/) (WHOQOL-BREF):** Semaglutide improved self-evaluated general health (ETD 0.48 [0.13–0.83]) and psychological health (ETD 1.51 [0.15–2.88]), but not overall quality of life or physical health domains.

- **DUDIT, FTND score, and cigarette consumption:** No significant differences between groups.

- **Spearman correlation:** Greater weight loss was significantly associated with greater reduction in heavy drinking days in the semaglutide group (rho=–0.40, p=0.0038), but not in the placebo group (rho=0.03, p=0.85).

### Subgroup Analyses

- **Severe AUD (DSM-5):** Significant treatment effect (ETD –12.0 [–19.4 to –4.6]). This subgroup comprised 92 of 108 participants.

- **Baseline 12–17 heavy drinking days:** Significant treatment effect (ETD –22.7 [–33.3 to –12.2]).

- **Moderate AUD subgroup and other baseline heavy-drinking strata:** No statistically significant effect detected, though authors attribute this to low power given the small numbers in each subgroup (as few as 17 participants per subgroup). Consistent directional trends toward benefit were observed across all subgroups.

## Adverse Events and Safety Profile

Event
Semaglutide (n=54)
Placebo (n=54)

Nausea
31 (57%)
4 (7%)

Constipation
19 (35%)
9 (17%)

Loss of appetite
19 (35%)
8 (15%)

Reflux
15 (28%)
1 (2%)

Diarrhoea
15 (28%)
11 (20%)

Fatigue
17 (32%)
10 (19%)

Food aversion
13 (24%)
1 (2%)

Abdominal pain
11 (20%)
4 (7%)

Vomiting
8 (15%)
1 (2%)

Elevated amylase (asymptomatic, above ULN)
4 (7%)
0

Hospital

Evidence Watch Reading Tool

### Read This Paper Through Nine Different Lenses

The same evidence can produce very different conclusions depending on the question being asked. Explore this study through multiple physician-guided interpretive frameworks.

OVERVIEW
Semaglutide reduces heavy drinking days by 13.7 percentage points in AUD-obesity patients.

#### Overview

Badge 1: ValueBadge 2: EvidenceBadge 3: Innovation

This study demonstrates that semaglutide, a GLP-1 receptor agonist, significantly reduces heavy drinking days in patients with alcohol use disorder and obesity. The treatment also led to substantial improvements in secondary outcomes such as weight loss and reduced alcohol craving scores.

The findings suggest a potential new therapeutic approach for AUD, particularly in individuals with comorbid obesity, offering hope for more effective treatments.

- Semaglutide reduced heavy drinking days by 13.7 percentage points compared to placebo.

- Significant weight loss and reduced alcohol craving scores were observed.

- GLP-1 receptor agonists may influence brain pathways involved in reward and craving.

Key Insight
Semaglutide significantly reduces heavy drinking days in patients with AUD and obesity.

#### Patient Takeaway

Badge 1: HopeBadge 2: TreatmentBadge 3: Research

For patients with alcohol use disorder and obesity, semaglutide offers a promising new treatment option. The study shows that it can significantly reduce heavy drinking days and improve related symptoms like weight loss and reduced craving.

While more research is needed to confirm long-term efficacy, this treatment could provide additional support for those seeking recovery from AUD.

- Semaglutide reduces heavy drinking days by 13.7 percentage points.

- Weight loss of 9 kg was observed in the semaglutide group.

- Reduced alcohol craving scores indicate potential psychological benefits.

Patient Takeaway
Semaglutide may offer a new treatment option for reducing heavy drinking days.

#### Clinician’s POV

Badge 1: EvidenceBadge 2: TreatmentBadge 3: Research

Clinicians can consider semaglutide as a potential adjunctive therapy for patients with alcohol use disorder and obesity. The study provides robust evidence of its efficacy in reducing heavy drinking days and improving related outcomes.

Further research is needed to explore the long-term benefits and safety, but this treatment could be an important addition to existing therapeutic options.

- Semaglutide reduces heavy drinking days by 13.7 percentage points.

- Significant weight loss and reduced alcohol craving scores were observed.

- GLP-1 receptor agonists may influence brain pathways involved in reward and craving.

Clinician Takeaway
Semaglutide shows promise as a treatment for reducing heavy drinking days in AUD-obesity patients.

#### A Skeptical Read

Badge 1: SkepticismBadge 2: EvidenceBadge 3: Research

While the study provides strong evidence of semaglutide’s efficacy, some skepticism remains regarding its long-term benefits and safety in treating alcohol use disorder. The treatment’s mechanism of action is not fully understood, and more research is needed to confirm these findings.

Clinicians should consider this treatment with caution and monitor patients closely for adverse effects.

- Semaglutide reduces heavy drinking days by 13.7 percentage points.

- Gastrointestinal side effects were common but mostly mild to moderate.

- Further research is needed to explore long-term efficacy and safety.

Skeptic Takeaway
While promising, semaglutide’s long-term benefits and safety in AUD require further investigation.

#### Study Critic

Badge 1: CriticismBadge 2: EvidenceBadge 3: Research

Critics may argue that the study’s focus on patients with comorbid obesity limits its generalizability to all AUD populations. Additionally, the treatment’s mechanism of action is not fully understood, and more research is needed to confirm these findings.

The study’s results should be interpreted with caution, and further [clinical trials](https://cedclinic.com/endocannabinoid-system-emotional-memory-ptsd-treatment/) are necessary to validate these outcomes in diverse patient groups.

- Study focused on patients with comorbid obesity.

- Mechanism of action for reducing alcohol consumption is not fully understood.

- Further research needed to confirm findings in diverse populations.

Critic Takeaway
Critics highlight the need for further research to validate semaglutide’s efficacy in diverse AUD populations.

#### Compared to Past Research

Badge 1: HistoryBadge 2: ResearchBadge 3: Context

Previous studies have suggested that GLP-1 receptor agonists may reduce alcohol consumption, but this study provides the first robust evidence in a randomized controlled trial setting. The findings build on preclinical and initial human studies indicating potential benefits of semaglutide for AUD.

This research contributes to the growing body of literature exploring novel treatment approaches for alcohol use disorder.

- Previous studies suggested GLP-1 receptor agonists may reduce alcohol consumption.

- This study provides robust evidence in a randomized controlled trial setting.

- Research builds on preclinical and initial human studies.

Historical Context
This study builds on previous research suggesting GLP-1 receptor agonists may reduce alcohol consumption.

#### Practical Considerations

Badge 1: PracticalBadge 2: ImplementationBadge 3: Application

Practically, semaglutide could be considered as an adjunctive therapy for patients with AUD and obesity. The treatment’s efficacy in reducing heavy drinking days and improving related outcomes suggests potential benefits for clinical practice.

Clinicians should monitor patients closely for adverse effects and consider individual patient profiles when deciding on treatment options.

- Semaglutide reduces heavy drinking days by 13.7 percentage points.

- Significant weight loss and reduced alcohol craving scores were observed.

- Gastrointestinal side effects were common but mostly mild to moderate.

Practical Takeaway
Semaglutide could be considered as an adjunctive therapy for AUD-obesity patients.

#### Future Directions

Badge 1: FutureBadge 2: ResearchBadge 3: Innovation

Future research should explore the long-term efficacy and safety of semaglutide in treating alcohol use disorder. Additional studies are needed to confirm these findings in diverse patient populations and to better understand the treatment’s mechanism of action.

The potential for GLP-1 receptor agonists as a novel treatment target for AUD is promising, but more [clinical trials](https://cedclinic.com/endocannabinoid-system-emotional-memory-ptsd-treatment/) are necessary.

- Further research needed to explore long-term efficacy and safety.

- Additional studies required in diverse patient populations.

- Mechanism of action for reducing alcohol consumption needs further investigation.

Future Research
Future research is needed to confirm semaglutide’s long-term benefits and safety in AUD.

#### Misreadings & Bad-Faith Takes

Badge 1: MisreadingBadge 2: ClarificationBadge 3: Accuracy

It is important to clarify that while semaglutide reduces heavy drinking days, it does not eliminate alcohol use disorder. The treatment should be considered as an adjunctive therapy alongside standard care like cognitive behavioral therapy.

Misreadings of the study’s findings could lead to unrealistic expectations about the treatment’s efficacy and potential side effects.

- Semaglutide reduces heavy drinking days but does not eliminate AUD.

- Treatment should be considered as an adjunctive therapy alongside standard care.

- Misreadings could lead to unrealistic expectations about efficacy and side effects.

Avoid Misreading
Semaglutide reduces heavy drinking days but is not a cure for AUD.

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What is semaglutide?

Semaglutide is a GLP-1 receptor agonist used primarily for [weight management](https://cedclinic.com/cannabis-metabolism-weight-management-science/) and diabetes, but recent studies suggest it may also help reduce alcohol consumption.

How effective was semaglutide in reducing heavy drinking days?

Semaglutide reduced heavy drinking days by 41.1 percentage points from baseline compared to a 26.4 percentage point reduction with placebo, resulting in an estimated treatment difference of –13.7 percentage points.

What were the secondary outcomes observed?

Secondary outcomes included reduced total alcohol consumption, fewer drinks per drinking day, lower alcohol craving scores, and significant weight loss.

Were there any adverse effects noted in the study?

The most common adverse events were gastrointestinal issues like nausea and constipation, which were mostly transient and mild to moderate.

What is the significance of this study for patients with alcohol use disorder?

This study suggests semaglutide could be a novel treatment option for reducing heavy drinking in patients with comorbid obesity and alcohol use disorder.

How does semaglutide work to reduce alcohol consumption?

The exact mechanism is not fully understood, but GLP-1 receptor agonists may influence brain pathways involved in reward and craving.

What are the implications for future research?

Future studies should explore the long-term efficacy and safety of semaglutide in treating alcohol use disorder, as well as its potential benefits in other populations.

Is this treatment available now?

Semaglutide is approved for [weight management](https://cedclinic.com/cannabis-metabolism-weight-management-science/) and diabetes but not specifically for alcohol use disorder. Its availability for AUD would depend on further clinical trials and regulatory approvals.

Who might benefit most from semaglutide treatment?

Patients with moderate to severe alcohol use disorder who are also obese may benefit the most, based on this study’s findings.

What is the next step in bringing semaglutide to market for AUD?

The next steps include additional clinical trials to confirm efficacy and safety, followed by regulatory submissions and potential approval for use in alcohol use disorder.

 

### Related

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### Verification & Medical Governance

- **Lead Clinical Author:** Benjamin Caplan, MD
- **Credentials:** Board Certified in Family Medicine (ABFM), Former CMO Canna Care Docs (250,000+ patients supervised), Founder & CMO CED Clinic & CED Foundation, Author of *The Doctor-Approved Cannabis Handbook* (Penguin Random House).
- **Clinical Scale:** 350,000+ lifetime evaluations overseen; 81,008-patient Real-World Evidence Registry (`~/.ced_rwe_vault.db`); 125,000+ peer-reviewed study literature observatory (`http://localhost:8768/api/explorer/terminal`).
- **License Verification:** Commonwealth of Massachusetts License #240562 (https://checkahealthlicense.mass.gov/).
- **NPI Registry:** 1962722637 (https://npiregistry.cms.hhs.gov/provider-view/1962722637).
- **Ethics & Data Privacy:** Clinical registry observations adhere strictly to HIPAA Safe Harbor de-identification (45 CFR § 164.514(b)) and criteria for secondary research exemption under 45 CFR § 46.104(d)(4).
