GLP-1s vs. Naltrexone and Acamprosate for Drinking Less: Evidence
If drinking less is your main goal, naltrexone and acamprosate are the evidence-backed choices. Both are approved for alcohol use disorder (AUD), and decades of trials stand behind them. GLP-1 drugs such as semaglutide are not approved for AUD as of October 2026. Two small randomized trials, the larger with 108 people over 26 weeks, plus observational studies point to a real effect, but they don't yet replace proven treatment.
Key takeaways
- Medications approved for AUD in the US are naltrexone (daily pill or monthly injection), acamprosate and disulfiram. No GLP-1 is on that list.
- A 2014 JAMA meta-analysis found one person avoids a return to drinking for every 12 treated with acamprosate, and one avoids a return to heavy drinking for every 12 treated with naltrexone.
- Two randomized semaglutide trials have reported benefits. A 2025 trial (n=48, 9 weeks) found less lab drinking and craving but no change in drinking days. A 2026 Lancet trial (n=108, 26 weeks) in people with AUD and obesity found fewer heavy-drinking days than placebo.
- A large Swedish registry study linked semaglutide use to 36% lower risk of AUD hospitalization. It was observational and did not directly compare drugs.
- If you have obesity or type 2 diabetes plus a drinking problem, ask your prescriber about both, but don't count on a GLP-1 to treat AUD by itself.
Side by side: approved AUD medicines vs. GLP-1s
| Medication | Approved for AUD? | How it's taken | Strongest evidence | What it showed | Key cautions |
|---|---|---|---|---|---|
| Naltrexone (oral) | Yes | Pill, usually once daily | Meta-analysis of many RCTs | NNT 12 to prevent return to heavy drinking; NNT 20 for any drinking | Can't be used with opioids; tell your doctor about liver or kidney disease |
| Naltrexone extended-release (Vivitrol) | Yes | Injection by a provider once a month | Approved product; same drug as oral naltrexone | Removes the daily-pill step | Must be opioid-free 7–14 days first; injection-site reactions; liver warnings |
| Acamprosate | Yes | Pill, three times daily | Meta-analysis of many RCTs | NNT 12 to prevent return to any drinking; no clear effect on heavy drinking | For people who have already stopped drinking; tell your doctor about kidney disease |
| Semaglutide (Wegovy, Ozempic) | No (off-label for AUD) | Weekly injection | Two RCTs (n=48, 9 weeks; n=108, 26 weeks); observational cohorts | Fewer heavy-drinking days (2026 trial, with obesity); less lab drinking and craving (2025 trial) | GI side effects; pancreatitis and other label warnings; no long-term AUD data |
| Liraglutide | No (off-label for AUD) | Daily injection | Observational data | Linked to lower AUD hospitalization in Swedish registry | Same class warnings; no AUD trials cited here |
Source: NIAAA; Jonas et al., JAMA 2014; Vivitrol; MedlinePlus (naltrexone, acamprosate); Hendershot et al., JAMA Psychiatry 2025; AJMC (Klausen et al., Lancet 2026); Lähteenvuo et al., JAMA Psychiatry 2025. NNT = number needed to treat for one additional person to benefit.
The approved options and how well they work
The National Institute on Alcohol Abuse and Alcoholism (NIAAA) lists three medications approved for AUD in the US. Naltrexone "helps reduce the urge to drink." Acamprosate eases the discomfort of early abstinence. Disulfiram causes unpleasant reactions when you drink (NIAAA, updated Feb. 2025).
The key evidence comes from a JAMA systematic review and meta-analysis of outpatient AUD treatment (Jonas et al., JAMA, 2014):
- Acamprosate: number needed to treat (NNT) of 12 to prevent one return to any drinking (16 trials, 4,847 people). It was not linked to fewer returns to heavy drinking.
- Oral naltrexone 50 mg: NNT of 20 to prevent a return to any drinking (16 trials, 2,347 people) and NNT of 12 to prevent a return to heavy drinking (19 trials, 2,875 people).
- Head-to-head: Trials comparing the two found no significant difference. The authors suggested dosing frequency, side effects and availability can guide the choice.
These medicines are meant to be combined with counseling or support, not used alone.
Practical differences
Oral naltrexone is usually a once-daily pill. You can't take it with opioids, and MedlinePlus advises telling your doctor about opioid use in the past 7 to 10 days and about any liver or kidney disease (MedlinePlus, naltrexone). The monthly injectable form, Vivitrol, is given by a provider. Its maker says you should stop drinking before starting it and be off opioids for 7 to 14 days. Its warnings include severe injection-site reactions and liver damage (Vivitrol).
Acamprosate is taken three times a day and is meant for people who have already stopped drinking (MedlinePlus, acamprosate). That makes it better suited to staying abstinent than to cutting back.
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What the GLP-1 evidence actually shows
The first randomized trial
The first randomized semaglutide trial for AUD was a phase 2 study published in JAMA Psychiatry in February 2025. Researchers at UNC Chapel Hill randomized 48 adults with AUD who were not seeking treatment to weekly semaglutide or placebo for nine weeks. Doses were low by obesity standards: 0.25 mg for four weeks, then 0.5 mg, with an optional 1.0 mg at week 9. Most participants (71%) were women (Hendershot et al., JAMA Psychiatry, 2025).
Compared with placebo, semaglutide:
- Reduced the amount of alcohol people drank in a lab drinking session, the trial's primary outcome.
- Reduced drinks per drinking day and alcohol craving.
- Was linked to greater reductions in heavy drinking days over time, an exploratory finding.
- Did not significantly change drinks per calendar day or the number of drinking days versus abstinent days.
There were no serious adverse events or treatment-related dropouts. The semaglutide group lost 5.05% of body weight, versus a 0.18% gain on placebo (Hendershot et al.). The limits are real: the trial was small and short, the lab analysis included only 25 people, and several outcomes were exploratory.
The larger 2026 trial
In April 2026, The Lancet published a double-blind trial from Copenhagen in 108 adults who were seeking treatment for AUD and also had obesity (BMI 30 or higher). Everyone received cognitive behavioral therapy plus either semaglutide 2.4 mg weekly or placebo for 26 weeks, and 88 completed the study (AJMC).
The share of heavy-drinking days fell by 41.1 percentage points with semaglutide versus 26.4 with placebo. Total alcohol intake and drinks per day also fell more, and the semaglutide group lost 11.2 kg versus 2.2 kg on placebo. Gastrointestinal effects were the most common side effects, and five participants stopped because of them (AJMC). Blood alcohol biomarkers supported the self-reported drinking data, according to the National Institutes of Health, which also noted that an earlier GLP-1 trial found no overall effect. The trial was run at a single center, had no follow-up after treatment ended, and its participants were mostly White (AJMC).
The observational data
A Swedish nationwide registry study followed about 228,000 adults with AUD for a median of 8.8 years. It compared periods when each person was using a medication with periods when the same person was not. Semaglutide use was linked to a 36% lower risk of AUD hospitalization (adjusted hazard ratio 0.64), liraglutide to 28% lower (0.72) and naltrexone to 14% lower (0.86) (Lähteenvuo et al., JAMA Psychiatry, 2025).
It's tempting to read that as "semaglutide beats naltrexone." The authors warn against it. Each drug was compared with non-use of its own class, not with the others, so the figures can't be ranked. The study also shows association, not causation, and GLP-1 users in it had obesity or type 2 diabetes. The authors call for randomized trials to confirm the findings (Lähteenvuo et al.).
Regulatory status as of October 2026
No GLP-1 medicine is FDA-approved to treat AUD. Wegovy's current labeling, approved in May 2026, lists cardiovascular risk reduction, chronic weight management and MASH with liver fibrosis as its indications. Alcohol use disorder is not among them (FDA Wegovy labeling, May 2026). Prescribing a GLP-1 only to reduce drinking would be off-label.
Who each approach fits
Naltrexone tends to fit if you...
- Want to cut down on heavy drinking, not necessarily quit completely.
- Don't use opioids now and don't expect to need opioid pain medicine.
- Would rather take a monthly injection than remember a daily pill (Vivitrol).
Acamprosate tends to fit if you...
- Have already stopped drinking and want help staying stopped.
- Take opioids, which rules out naltrexone.
- Can manage a three-times-daily schedule.
A GLP-1 conversation may make sense if you...
- Already qualify for a GLP-1 because of obesity, overweight with a related condition, or type 2 diabetes, and also want to drink less.
- Understand that any effect on drinking is a possible bonus, not an approved treatment.
- Are willing to use it alongside, not instead of, AUD treatment and support. Whether combining a GLP-1 with naltrexone or acamprosate adds benefit hasn't been tested in the trials cited here.
The verdict
For drinking less, naltrexone and acamprosate win on evidence. They're approved for AUD, backed by many randomized trials, and can work alongside counseling. Naltrexone fits people who want to cut heavy drinking; acamprosate fits people who have already stopped. GLP-1s are the most interesting new idea in this field: two randomized trials showed fewer heavy-drinking days, less drinking per occasion and less craving, and large registry data point the same way. But they aren't approved for AUD, haven't been tested beyond six months, and haven't been compared directly with standard treatment. If you also have a weight or diabetes reason to take a GLP-1, it's reasonable to ask your prescriber whether it could help with drinking too, as an addition to AUD treatment rather than a replacement.
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For help finding AUD treatment, NIAAA's guide to finding and getting help explains the options and how to find care (NIAAA).
Frequently asked questions
Is semaglutide approved to treat alcohol use disorder?
No. As of October 2026, no GLP-1 is FDA-approved for alcohol use disorder. The medications approved for AUD in the US are naltrexone, acamprosate and disulfiram.
Does Ozempic or Wegovy reduce drinking?
Two randomized trials suggest semaglutide can help. A 48-person, nine-week trial found less lab drinking and craving, and a 108-person, 26-week trial in people with AUD and obesity found fewer heavy-drinking days than placebo. Neither makes it an approved AUD treatment.
How well do naltrexone and acamprosate work?
A 2014 JAMA meta-analysis found an NNT of 12 for acamprosate to prevent a return to any drinking, and an NNT of 12 for naltrexone to prevent a return to heavy drinking. Head-to-head trials found no significant difference between them.
Did a study show semaglutide works better than naltrexone?
No direct comparison exists. A Swedish registry study linked semaglutide to a 36% lower risk of AUD hospitalization and naltrexone to 14% lower, but the authors cautioned that the drugs can't be ranked because each was compared only with its own non-use.
Who should consider naltrexone versus acamprosate?
Naltrexone generally fits people trying to cut heavy drinking who don't use opioids. Acamprosate is meant for people who have already stopped drinking. Your prescriber can help you choose.
Sources
- NIAAA: Treatment for Alcohol Problems: Finding and Getting Help (updated Feb. 2025)
- Jonas DE, et al. Pharmacotherapy for Adults With Alcohol Use Disorders in Outpatient Settings. JAMA, 2014
- Hendershot CS, et al. Once-Weekly Semaglutide in Adults With Alcohol Use Disorder. JAMA Psychiatry, 2025
- Lähteenvuo M, et al. Repurposing Semaglutide and Liraglutide for Alcohol Use Disorder. JAMA Psychiatry, 2025
- AJMC: GLP-1s reduce heavy drinking days in patients with obesity and alcohol use disorder (April 2026)
- NIH: Adding weekly GLP-1 to cognitive behavioral therapy further reduces heavy drinking (April 2026)
- Vivitrol (naltrexone extended-release injectable suspension): patient information
- MedlinePlus: Naltrexone
- MedlinePlus: Acamprosate
- FDA: Wegovy approval package and labeling, NDA 215256/S-031 (May 2026)
Medical disclaimer: This article is general information, not medical advice, and does not replace a licensed clinician who knows your history. Approvals, labels, coverage and prices change; check the linked sources and talk with your prescriber or pharmacist before making decisions about any medication.