Do GLP-1's Change Your Personality?

The arrival of summer means beach season is calling for many, which may lead some to chase the perfect swimsuit physique. A 2025 Gallup poll showed that 52% of Americans want to lose weight but that only 26% are actively working towards this goal. GLP-1 agents (eg, semaglutide, tirzepatide) are increasingly utilized for weight loss in the United States and are part of patient goals. Despite cost limitations, surveys show that 1 in 8 Americans is currently prescribed a GLP-1 agonist for weight loss, and the global market for GLP-1’s is expected to surpass $200 billion by the of the decade. GLP-1 efficacy for weight loss may be unparalleled, but recent reports describe unwanted effects on mood and drive, raising the question: Do GLP-1’s change your personality?

GLP-1’s have emerging broad utility. Beyond weight loss and cardiovascular benefits, they have been show to reduce incidence of breast cancer in women and halt progression of Parkinson’s disease, among other effects. Ongoing research also suggests a role for GLP-1’s in the treatment of substance use disorders. Neurochemically, the dampening of “food noise” by these drugs may also decrease activity in the brain’s reward pathways that influence alcohol use, illicit drug use, and compulsive behaviors.

For those without substance use disorders, however, this effect may manifest as a bothersome lack of drive, emotional blunting, inability to feel pleasure in their usual day-to-day pursuits, or decreased ambition. In some instances, GLP-1’s may also adversely impact libido. Rarely, these mood changes can be severe and associated with suicidal ideation, although current guidance from the Food and Drug Administration suggests no causal risk.

Our early experience and limited data with the potential psychiatric consequences of GLP-1 agonists means that many questions about their risk and benefit profile are not answerable. But history provides some cautionary guidance. Rimonabant, a cannabinoid receptor antagonist meant to block potential brain reward responses to eating, was released in June 2006 in the United Kingdom as an adjunct treatment for weight loss and metabolic disturbances. Although the signal for its intended outcomes was positive, public fervor for the drug diminished when the FDA ultimately rejected approval in the United States because of an increased risk of adverse psychiatric outcomes in the treatment group, including two deaths by suicide.

To be sure, GLP-1 agonists have an important place in the clinical care of obesity, as well as many other potential uses. Research and development will assuredly advance and bring us newer and more effective agents for weight loss (eg, reatrutide). However, overzealous use must be tempered by a concerted and careful effort to assess risk and benefits until further research provides is available. For those taking these potentially life-changing medications, a healthy respect for mental well-being must also be part of the weight-loss journey.