I quit drinking after getting headaches, looking at the evidence and deciding it wasn’t worth it. Most people with alcohol use disorder can’t just decide. Fewer than 2% of them ever get medication for it, and the drugs we do have (naltrexone, acamprosate, disulfiram) produce small effects and get almost no uptake.
This drug could be different and have big impact.
Lilly has a drug Brenipatide in late-stage trials called brenipatide. Same class as tirzepatide (Mounjaro/Zepbound), but engineered with a much longer half-life. Dosed once a month, subcutaneous. That schedule alone is a big deal for addiction medicine, where adherence is half the battle. Vivitrol, the monthly depot of naltrexone, outperforms the daily pill for exactly that reason.
Two Phase 3 AUD trials are actively enrolling (RENEW-ALC-1 and RENEW-ALC-2), 1,100 patients each. Separate trials are running for smoking relapse, opioid use disorder, bipolar disorder, and asthma. Readouts start landing in 2027.
Here’s why Lilly is going hard at this. The signal in the existing data is almost hard to believe.
A BMJ study published last month followed 606,000 veterans on GLP-1s vs. SGLT2 inhibitors. In people with no prior substance use disorder, GLP-1 users had 18% less alcohol use disorder, 20% less nicotine, and 25% less opioid use disorder. In people with an existing SUD, GLP-1 use was associated with 39% fewer overdoses and 50% fewer substance-related deaths over three years.
A JAMA Psychiatry Phase 2 trial of semaglutide in AUD (48 people, 9 weeks) showed medium-to-large effect sizes on drinking outcomes and reduced cravings. That matters because approved AUD meds like naltrexone typically show only small effect sizes. And the semaglutide group hit those numbers at the two lowest clinical doses.
So here’s the case. A drug class that wasn’t designed for addiction is already outperforming drugs that were. Lilly is now testing a molecule engineered for it, with a dosing schedule that solves the adherence problem, in the largest randomized AUD trials ever run.
What makes this interesting despite all that is Lilly isn’t the only shot on goal. Baseline Therapeutics launched in January specifically to run Phase 3 trials of their own GLP-1 candidate (BT-001) in AUD. The VA is planning a semaglutide trial. Altimmune is in Phase 2 with pemvidutide. Thirty-three GLP-1 trials for substance use disorders are currently registered on ClinicalTrials.gov. Even if half of them fail, the other half would hand us more pharmacotherapy than AUD has gotten in a lifetime.
If these trials turn out positive, it’s the biggest thing to happen to addiction medicine in a generation.
If you want to go deeper on this, the JAMA Psychiatry author interview with Hendershot and Klein on the semaglutide AUD trial is solid and short. The Might Ramble Podcast #17 with Lorenzo Leggio is the single best conversation I’ve found on the mechanism and the state of the field. NPR’s Jon Hamilton had a tight story on the veterans data that’s worth the ten minutes.