For the first time, researchers show that tirzepatide – the active ingredient in the diabetes and weight-loss drug Mounjaro – reduces alcohol intake as well as relapse-like behaviors in rats and mice. The findings are considered relevant in the search for new treatments for alcohol use disorder.

Researchers at the University of Gothenburg have previously demonstrated that semaglutide, found in the diabetes and weight-loss drugs Ozempic and Wegovy, reduces alcohol consumption in rats. In the current study, published in the journal eBioMedicine, the focus shifts to tirzepatide and Mounjaro.

Voluntary alcohol consumption fell by more than half in animals treated with tirzepatide. The drug also prevented relapse-like drinking. After a period without alcohol, the animals did not increase their drinking; instead, it decreased compared with earlier levels.

“We observed clear and robust reductions in long-term alcohol consumption, binge-like drinking, and relapse-like drinking in both male and female animals. What makes this study particularly compelling is that it also provides new insight into how this class of drugs may influence the brain’s reward system,” says Christian Edvardsson, a doctoral student in pharmacology at the Sahlgrenska Academy, University of Gothenburg.

Blunting alcohol’s effects
Tirzepatide, the first medication to act as a dual agonist at receptors for the satiety hormones GIP and GLP-1, is approved for the treatment of type 2 diabetes and is widely used in clinical practice. Because its safety profile has been extensively studied, this may facilitate future research into its potential role in alcohol use disorder.

In the study, the researchers found that tirzepatide attenuated alcohol-induced effects on dopamine, a key neurotransmitter in the brain’s reward system that contributes to alcohol’s reinforcing properties. The effect appears to be mediated, at least in part, through the lateral septum, a brain region linked to motivation, reward, and relapse in both animals and humans. The findings offer a possible neurobiological explanation for earlier observations that similar medications can reduce alcohol consumption and craving.

In the lateral septum, the researchers also identified changes in histone-related proteins that influence whether genes are switched on or off. Alterations in these proteins have previously been associated with substance use and addiction. However, the study does not show that these changes in themselves cause the reduction in alcohol consumption. Rather, the results suggest that they may form part of the biological mechanisms affected by tirzepatide.

Future treatment options
The study was conducted by researchers at the University of Gothenburg in collaboration with colleagues at the Medical University of South Carolina. It combined intake and behavioral tests with measurements of neurotransmitter levels in the brain and molecular analyses.

“This is not yet a new treatment for alcohol use disorder. But the findings reinforce the view that drugs targeting these neural systems may be relevant to investigate further as potential treatment options,” says Elisabet Jerlhag Holm, Professor of Pharmacology at the Sahlgrenska Academy, University of Gothenburg.

Study: Tirzepatide reduces alcohol drinking and relapse-like behaviours in rodents,