Once-Weekly Semaglutide in Adults With Alcohol Use Disorder
Why this work is in the frame
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Bibliographic record
Abstract
Importance: Preclinical, observational, and pharmacoepidemiology evidence indicates that glucagon-like peptide 1 receptor agonists (GLP-1RAs) may reduce alcohol intake. Randomized trials are needed to determine the clinical significance of these findings. Objective: To evaluate the effects of once-weekly subcutaneous semaglutide on alcohol consumption and craving in adults with alcohol use disorder (AUD). Design, Setting, and Participants: This was a phase 2, double-blind, randomized, parallel-arm trial involving 9 weeks of outpatient treatment. Enrollment occurred at an academic medical center in the US from September 2022 to February 2024. Of 504 potential participants assessed, 48 non-treatment-seeking participants with AUD were randomized. Intervention: Participants received semaglutide (0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks, and 1.0 mg for 1 week) or placebo at weekly clinic visits. Main Outcomes and Measures: The primary outcome was laboratory alcohol self-administration, measured at pretreatment and posttreatment (0.5 mg/week). Secondary and exploratory outcomes, including prospective changes in alcohol consumption and craving, were assessed at outpatient visits. Results: Forty-eight participants (34 [71%] female; mean [SD] age, 39.9 [10.6] years) were randomized. Low-dose semaglutide reduced the amount of alcohol consumed during a posttreatment laboratory self-administration task, with evidence of medium to large effect sizes for grams of alcohol consumed (β, -0.48; 95% CI, -0.85 to -0.11; P = .01) and peak breath alcohol concentration (β, -0.46; 95% CI, -0.87 to -0.06; P = .03). Semaglutide treatment did not affect average drinks per calendar day or number of drinking days, but significantly reduced drinks per drinking day (β, -0.41; 95% CI, -0.73 to -0.09; P = .04) and weekly alcohol craving (β, -0.39; 95% CI, -0.73 to -0.06; P = .01), also predicting greater reductions in heavy drinking over time relative to placebo (β, 0.84; 95% CI, 0.71 to 0.99; P = .04). A significant treatment-by-time interaction indicated that semaglutide treatment predicted greater relative reductions in cigarettes per day in a subsample of individuals with current cigarette use (β, -0.10; 95% CI, -0.16 to -0.03; P = .005). Conclusions and Relevance: These findings provide initial prospective evidence that low-dose semaglutide can reduce craving and some drinking outcomes, justifying larger clinical trials to evaluate GLP-1RAs for alcohol use disorder. Trial Registration: ClinicalTrials.gov Identifier: NCT05520775.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it