Ozempic and other semaglutide-based medications are known for their appetite-suppressing effects. Recent studies show that new oral drugs from the GLP-1 family can also reduce the pleasure derived from eating.

Features of GLP-1 Medications

Weight loss and diabetes treatments such as semaglutide and Ozempic belong to the GLP-1 group. A study supported by the U.S. National Institutes of Health (NIH) has uncovered a previously unknown mechanism by which some new oral drugs in this class affect the brain.

Impact on Eating Behavior

In mouse experiments, these drugs reduced food intake driven by pleasure rather than by energy needs. This effect is linked to changes in activity within the brain’s reward system, located deep within its structures. This pathway differs from previously studied appetite control mechanisms associated with drugs like semaglutide.

Oral Medications and Their Advantages

Oral GLP-1 drugs, such as FDA-approved orforglipron and the experimental danuglipron, are small-molecule GLP-1 receptor agonists. Unlike large peptide-based drugs (for example, semaglutide used in Ozempic, Wegovy, and Rybelsus), these can be taken as tablets and may be cheaper to produce compared to injectable forms.

Mechanisms of Action in the Brain

It has been well established how peptide GLP-1 drugs reduce hunger-driven eating by acting on the hypothalamus and hindbrain. However, the effects of small-molecule GLP-1 drugs after entering the brain have been less studied. To investigate this, researchers used gene editing to make mouse GLP-1 receptors more similar to those in humans.

New Insights into the Reward System

During experiments, mice were given orforglipron or danuglipron, and researchers analyzed activity in different brain regions. The drugs affected not only areas involved in appetite regulation but also activated the central amygdala—a region linked to desire and reward. This area is located deeper than previously thought, and its activation reduced dopamine release in key parts of the brain’s reward system when eating for pleasure.

Future Applications

The findings suggest that oral GLP-1 drugs may influence not only physical hunger but also weaken pleasure signals that make certain foods especially appealing. Future research will explore whether these drugs can also reduce cravings for substances other than food, including psychoactive compounds.

Funding and Regulatory Details

The study was supported by grants from the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of General Medical Sciences (NIGMS), the National Heart, Lung, and Blood Institute (NHLBI), and the National Cancer Institute (NCI) of the United States. This work was not a clinical trial, was not related to a product approval application, and was not evaluated by the FDA for any claimed indications.