Popular diabetes drugs show promise curbing alcohol cravings in lab studies
GLP-1 receptor agonists—the blockbuster medications behind Ozempic and similar weight-loss treatments—appear to reduce alcohol consumption and reward-seeking behavior in animal models, according to new preclinical research. If validated in humans, the finding could open a vast new market for these drugs while offering millions struggling with alcohol addiction a potential treatment option.
Originaltitel: GLP-1 and Alcohol-Related Behaviors: Insights From Preclinical Studies.
GLP-1-receptoragonister öppnar nya vägar för alkoholmissbruksbehandling. Sahlgrenska akademin i Göteborg dokumenterar att befintliga GLP-1R-agonister — både kortverkande (exenatide) och långverkande varianter (liraglutide, semaglutide) — minskar alkoholintag och alkoholsökande beteende i förkliniska modeller. Mekanismen verkar primärt gå genom att substanserna dämpar alkoholens belöningsvärde via dopaminvägar i nucleus accumbens och minskar konditionerad platsönskvärdhet. Både korta och långa GLP-1R-agonister presterar konsistent, oavsett kön hos försöksdjuren. För branschen är detta affärsmässigt relevant eftersom godkända diabetesmediciner redan marknadsförs för vikt och nu får utvärdering mot alkoholberoende — ett område med begränsat farmakologiskt utbud. Utvecklingen kan förkorta tid till klinisk prövning och öka läkemedelsvärde genom nytt indikationsområde. Andra faktorer som magsäckstömning och illamående kan också spela roll.
Glucagon-like peptide-1 (GLP-1) has gained attention for its broad physiological effects, and both short-acting (exenatide/exendin-4 [Ex4]) and long-acting (liraglutide, dulaglutide, semaglutide) GLP-1 receptor (GLP-1R) agonists have been approved for type 2 diabetes and/or obesity. Initial preclinical research has highlighted the role of GLP-1 and its receptor in the pathophysiology of alcohol use disorder (AUD) and their potential use in the treatment of AUD. Specifically, systemic treatment of Ex4 reduces alcohol intake, the motivation to consume alcohol, and relapse-like behavior in male animals. Similarly, alcohol consummatory behaviors are reduced in male or female animals treated with either of the long-acting GLP-1R agonists. Moreover, both short- and long-acting GLP-1R agonists consistently attenuate the rewarding properties of alcohol, as measured by locomotor stimulation, dopamine release in the nucleus accumbens, and conditioned place preference in male mice. Because alcohol consumption is largely driven by alcohol-induced reward, it is hypothesized that GLP-1R agonists attenuate the rewarding effects of alcohol, thereby decreasing alcohol intake. However, it should be emphasized that other factors, including altered gastric emptying, nausea, and enhanced stress, may also contribute to these effects. Taken together, these preclinical studies offer insight into the potential use of GLP-1R agonists in the treatment of AUD.