Ozempic (semaglutide) shows huge reductions in high-risk heavy drinking, in first-ever clinical trial

Powerful findings in Christian Hendershot's RCT w/ 48 non-treatment seekers and relatively low doses of semaglutide.

Placebo: yellow, Semaglutide (Ozempic): blue

I reported last summer on preliminary findings from Christian Hendershot’s randomized controlled trial of semaglutide (Ozempic) in 48 non-treatment seeking adults with alcohol use disorder (AUD). JAMA Psychiatry just published the paper.  

The trial shows a huge dose-dependent reduction in heavy drinking days, at a relatively low dose of Ozempic:

Effect sizes for heavy drinking days and drinks per drinking day reached the large range (d > 0.80) at the 0.5 mg/week dose, with objective laboratory data also suggesting large effect sizes on self administration… By comparison, approved (and effective) AUD medications, including naltrexone, generally show small effect sizes in both clinical trials and laboratory studies of self-administration and other outcomes.

There are a bunch of really important findings to note here:

• This was a 9-week study. Ozempic dosing starts low and increases slowly, month by month. The results on heavy drinking were huge when participants were only at a 0.5mg dose, which is *half* of a baseline maintenance dose of Ozempic. In a longer study, the effect would likely be even larger.

• The effect size for reducing heavy drinking is far larger than what has been shown for oral or injectable naltrexone (Vivitrol). If confirmed in larger studies, semaglutide will become the new standard of care.

• Semaglutide is combinable with naltrexone because they work on different mechanisms. People who have anecdotally reported using both have seen tremendous reductions in cravings and consumption.

• The study included participants with BMIs of 23 or higher—showing efficacy even in normal weight individuals.

• The trial did not show a reduction in the number of drinking days. People still drank on roughly the same number of days, but when they drank, they drank a low to moderate amount. This is a key to understanding GLP-1s and the upcoming revolution in addiction treatment—there will be more and more medications that can support long-term moderation without requiring abstinence. At the same time, abstinence will remain a goal for many people, and these medications will make that goal far more achievable.

• The study also showed an intriguing drop in the number of cigarettes smoked per day, albeit with a low sample size of smokers and an increase in smoking in the placebo group.

The paper also speaks directly to the lack of innovation in addiction medicine, which is the focus of CASPR’s policy work:

Since the FDA approval of the first AUD medication (disulfiram) in 1951, only 2 medications (naltrexone and acamprosate) have received subsequent FDA approval for AUD. The rate of 1 new approval every 20 to 25 years is inadequate and is in stark contrast with the pace of FDA approvals for diabetes medications, which now outnumber AUD medication approvals 20-fold.

Christian Hendershot presenting his findings at CPDD 2024 in Montreal

How do we bring this medicine to patients and doctors?

One of CASPR’s primary goals is to run a phase 3 trial of a GLP-1 for AUD. We have an incredible team hard at work on this goal, with initial funding from Arnold Ventures and an advisory board of experts and global leaders in addiction and incretins. We believe a pivotal trial and global approvals of a GLP-1 for AUD is the largest ROI opportunity in public health today.

CASPR maintains the most comprehensive and up-to-date article reviewing research on GLP-1s for substance use disorders. These new results will be added today. Lots more, including patient reports and doctors who are already prescribing GLP-1s for addiction can be found here. For more news and updates, subscribe below— everything we publish is free.