In target trial emulations with 120M+ EHRs, tirzepatide reduced incident AUD risk by 53% (HR 0.47) and semaglutide by 32% (HR 0.68) vs DPP-4 inhibitors, while liraglutide and dulaglutide showed no benefit.
53% AUD reductionTirzepatide halved the risk of developing alcohol use disorder in diabetic patients — stronger than any existing AUD medication
What the researchers found
AUD risk reduction vs DPP-4i: tirzepatide HR 0.47 (0.29-0.75); semaglutide HR 0.68 (0.52-0.89); liraglutide and dulaglutide: NS. Tirzepatide vs liraglutide head-to-head: HR 0.47 (0.24-0.92).
Why it matters
AUD affects 29 million Americans with few effective medications. Two widely available drugs showing 32-53% AUD risk reduction could be rapidly repurposed.
How the study worked
Target trial emulations using Truveta EHR database (120M+ patients), 4 cohorts comparing tirzepatide/semaglutide/liraglutide/dulaglutide to DPP-4i, 1:1 propensity-score matching, 18-month follow-up for incident AUD.
What this study cannot tell us
Observational EHR data. AUD identified by ICD codes, which may undercount. Cannot determine if patients actually reduced drinking or just received fewer AUD diagnoses.
How to read the evidence
Target trial emulation from 120M+ EHR database with propensity matching. Strong real-world evidence, though observational.
When this study was published
Published in 2025 using Truveta database.
The bigger picture
The differential effects among GLP-1 drugs suggest specific pharmacological properties (possibly GIP co-agonism) drive anti-addiction effects, not just GLP-1 receptor activation.
Questions still open
- Does GIP receptor agonism explain tirzepatide's superiority for AUD?
- Would these drugs help non-diabetic patients with AUD?
- Should addiction medicine specialists prescribe tirzepatide off-label for AUD?
Common questions
Which GLP-1 drug is best for reducing alcohol use disorder risk?
Why do some GLP-1 drugs help with alcohol but others don't?
Read the original research
Relative efficacy of GLP-1 and GLP-1/GIP receptor agonists in the prevention of alcohol-use disorders using a target trial emulation approach.
Diabetes, obesity & metabolism, 28(1), 137-150
Citation
Henney, Alex E; Riley, David R; Heague, Megan; Roberts, Carl A; Hydes, Theresa J; Anson, Matthew; Hughes, David M; Alam, Uazman; Cuthbertson, Daniel J. (2026). Relative efficacy of GLP-1 and GLP-1/GIP receptor agonists in the prevention of alcohol-use disorders using a target trial emulation approach.. Diabetes, obesity & metabolism, 28(1), 137-150. https://doi.org/10.1111/dom.70169