GLP-1 Drugs: How Ozempic and Wegovy Curb Cravings for Food and Alcohol

A synthesis of recent research indicates that GLP-1 receptor agonists—medications including Ozempic and Wegovy—reduce consumption of food and alcohol through action on the lateral septum, a brain region involved in reward processing and emotional regulation.

Mechanism of Action

GLP-1 receptor agonists were originally developed to treat type 2 diabetes by mimicking the GLP-1 hormone, which stimulates insulin release, slows digestion, and increases satiety. A side effect of these medications is significant weight loss.

Human studies have also observed reduced alcohol consumption in patients taking these drugs, while preclinical studies in animals have suggested similar effects on cocaine, amphetamines, opiates, and nicotine.

Brain Region Involvement

The lateral septum—a structure involved in emotional regulation and reward processing—contains a high density of GLP-1 receptors. Researchers note that the traditional reward circuitry, including the ventral tegmental area (VTA) and nucleus accumbens (NAc), lacks significant GLP-1 receptor density.

The lateral septum receives input from the hippocampus, which contains place cells that encode spatial and temporal information. Lateral septum neurons respond to rewards, integrating reward context with spatial-temporal data. Historical studies from 1953 documented that damage to the lateral septum increases aggression, while stimulation reduces aggression.

Experimental Findings

In experiments conducted with mice, researchers activated GLP-1 receptors directly in the lateral septum, which reduced food and alcohol intake. Further observations indicated that GLP-1 medications reduce a specific type of neural activity in the lateral septum, potentially impairing its communication with other brain regions.

Broader Implications

The findings suggest the lateral septum plays a role in cravings and reward processing. Researchers propose that understanding this mechanism may inform new treatment approaches for obesity, alcohol dependence, and other substance use disorders.