Body
View this post on the web at https://onthepen.substack.com/p/semaglutide-and-alcohol-a-new-study
There’s a particular kind of exhaustion that comes with alcohol use disorder. Not just the physical kind, though that’s real too. I’m talking the kind that settles into your bones after years of trying, having minimal success, and trying again. After being told, in ways spoken and unspoken, that the problem was really just a lack of willpower. That if you really wanted it badly enough, you’d find your way out eventually. Sound familiar?
If you’ve lived inside the obesity fight, you know this cycle all too well. The same cycle of white knuckle effort and utter disappointment. The same medical shrug. The same story that put the weight of a biological condition squarely on the shoulders of the person carrying it. Two different diagnoses. The same long loneliness. This week, the condition that has been waiting even longer for a real pharmacological answer got some news. And the drug at the center of it is one you already well know.
Researchers in Copenhagen just published a randomized controlled trial in The Lancet [ https://substack.com/redirect/f4aaa0dd-0168-4075-ac83-a84505495628?j=eyJ1IjoiNGl3b2U2In0.sVDxRtmZ85v8kfdamY0krRXGMy3p768BWtuZifRB-Zs ], one of the most respected medical journals in the world, testing whether semaglutide, the active ingredient in Wegovy and Ozempic, could reduce heavy drinking in people with alcohol use disorder. The results were clear enough that they’ll be difficult for the medical community to set aside. People in the study who received weekly semaglutide injections reduced their heavy drinking days by 41% over six months. People who received a placebo, a salt water injection, reduced theirs by 26%. That gap, roughly 14 percentage points, is statistically robust and clinically meaningful. Semaglutide didn’t just help a little. It helped in a way that showed up clearly against a control group that was also receiving therapy and weekly check-ins, conditions that already tend to move the needle on their own. In the obesity world, we call those “lifestyle modifications”.
The trial enrolled 108 people, split evenly between the drug and placebo. Everyone received cognitive behavioral therapy across the 26 weeks. By the end, the people on semaglutide were not only having fewer heavy drinking days. They were also drinking less per drinking day, reporting significantly less craving, showing improved liver enzyme numbers, and losing considerably more weight than the placebo group.
For decades, the FDA has approved exactly three medications for alcohol use disorder: disulfiram, acamprosate, and naltrexone. Three medications for a condition that accounts for 5% of deaths worldwide every year. Those medications help some people, and that certainly matters. It matters in the same way that phentermine and orlistat mattered to obesity. A useful way to think about how well a treatment works is something called the number needed to treat, which captures how many people have to take the drug for one person to meaningfully benefit. For the existing approved medications, that number sits at 7 or higher. For semaglutide in this trial, it was 4.3. That gap represents real people, and real outcomes that currently aren’t happening for them.
What makes this study harder to dismiss than a self-reported survey alone is that the researchers also measured a blood biomarker called phosphatidylethanol, which reflects actual alcohol intake independent of what people say. Drinking diaries and questionnaires are useful, but they carry the weight of memory and motivation. The biomarker confirmed what the self-reports showed, and that convergence matters. When two different kinds of evidence point in the same direction, the signal gets stronger.
This study enrolled people who were obese, BMI of 30 or above, because prior research suggested GLP-1 medications might work better in that population. That means we don’t yet know whether the same effect holds for people with AUD who aren’t carrying extra weight, and that’s a meaningful gap given how many people live with alcohol use disorder across a wide range of body types. The trial also ran only 26 weeks, with no follow-up data collected after it ended, so there’s no way to know yet whether the gains hold a year out, or what happens when someone stops the drug. Side effects were real and worth naming honestly. More than half of the people on semaglutide experienced nausea, along with constipation, reflux, and fatigue at higher rates than the placebo group. Most of those effects were temporary and mild to moderate, but this is not a medication that asks nothing of your body. And it bears repeating that this was one trial, 108 people, in one city in Denmark, with a study population that was predominantly White. The researchers themselves are careful to say that larger, more diverse studies are needed before anyone should consider using this drug off-label for AUD.
This is just the beginning. Eli Lilly has a dual GLP-1/GIP co-agonist called brenipatide that is being looked at for a whole host of nueralogical disorders. A large phase 3 trial with a potential submission for approval and an actual indication will begin this year. The incretin class of medications are serving up hope to many people fighting various addictions.
There are an estimated 8 million Americans living with both obesity and problematic alcohol use. For them, a drug already prescribed and in many cases covered for weight loss may be doing something else quietly. Despite several years of anecdotal evidience, science is now meaningfully catching up to the potential benefits of these medications. For the broader population of people with AUD, this study adds meaningful weight to a growing body of evidence that GLP-1 receptor agonists deserve serious investigation as a treatment for addiction, not just metabolism. The door has been stuck for a very long time. This research doesn’t fling it open, but it moves it. And for people who have been pushing on it for years, that is not nothing.
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