GLP-1s Linked to 42% Lower Risk of Anxiety, Depression

• A new study found that people taking GLP-1 drugs like Ozempic and Wegovy had a lower risk of worsening depression and anxiety.
• The participants also had fewer hospitalizations and required less sick leave from their jobs.
• Experts say the drugs’ effects on dopamine signaling and brain inflammation could account for the benefits.
• It’s too soon to recommend GLP-1s as a primary treatment for mental health disorders. Further clinical trials are still needed.

Researchers say people living with diabetes often face a higher risk of developing mental health conditions.

Now, a large national study from Sweden found that certain medications commonly prescribed for diabetes and weight loss — specifically GLP-1 receptor agonists like Ozempic and Wegovy — may also help reduce the risk of worsening mental illness in people with anxiety or depression.

The findings, published in the April issue of The Lancet Psychiatry, offer hope for dual benefits in treating both metabolic and mental health issues. While promising, the researchers caution that further clinical trials are needed.

The study analyzed health data from 95,490 people in Sweden who were diagnosed with depression, anxiety, or both, and were also prescribed diabetes medications between 2009 and 2022.

The study compared periods when individuals were taking these medications to periods when they were not, using a “within-individual” design. This approach means each person acted as their own control, reducing the influence of factors like age, gender, or overall health that do not change over time.

Data were gathered from national electronic health registers, including hospital admissions, sick leave records, and death registries, allowing researchers to track worsening mental health events.

The primary outcome was a composite measure that included psychiatric hospitalizations, extended sick leave for psychiatric reasons, hospitalization due to self-harm, or death by suicide.

Secondary outcomes examined worsening of depression or anxiety separately, substance use disorders, and self-harm incidents.

The study also compared GLP-1 receptor agonists with other second-line diabetes medications like empagliflozin (Jardiance), dapagliflozin (Farxiga), and sitagliptin (Januvia) to see how these medications stacked up against each other in terms of mental health effects.

Statistical models adjusted for time-varying factors such as the order and duration of medication use and concurrent treatment with other psychiatric or antidiabetic drugs.

The aim was to isolate the effects of GLP-1 receptor agonists on mental health as much as possible within the observational data.

Over an average follow-up of 5.2 years, about 23.5% of the cohort used GLP-1 receptor agonists, with semaglutide and liraglutide being the most common.

The study revealed that use of semaglutide was associated with a 42% lower risk of worsening mental illness compared to periods when the same individuals were not taking GLP-1 receptor agonists.

Liraglutide also showed a beneficial effect, though less pronounced, with an 18% reduced risk. In contrast, exenatide and dulaglutide did not show significant associations with mental health outcomes.

When looking at specific mental health conditions, semaglutide use was linked to significantly lower risks of worsening depression, anxiety, and substance use disorders. Liraglutide was associated primarily with reduced risk of worsening depression. Additionally, GLP-1 receptor agonists as a group were associated with a lower risk of self-harm.

Compared directly with other second-line antidiabetic medications, semaglutide was again associated with better mental health outcomes, suggesting its benefits extend beyond glucose control alone. The study also found that these associations held true even when accounting for factors such as sex and the type of mental health diagnosis at study entry.

Additionally, the reduced risk of worsening mental illness was reflected not only in fewer psychiatric hospitalizations but also in reduced sick leave due to mental health reasons, which has implications for work capacity and quality of life.

The researchers took care to rule out potential biases, such as effects due to the sequence of medication use or carryover effects between treatment periods. Their analyses remained consistent when excluding initial days after starting or stopping medication and when focusing on medication use after official approval dates.

Lauren Grawert, MD, clinical advisor at The Garden New Jersey, said it’s believed that GLP-1 medications can provide psychiatric benefits because they can cross the blood-brain barrier and bind to brain regions associated with the reward system. Grawert wasn’t involved in the study.

“These medications may affect the way the brain responds to dopamine signals in these areas, decreasing the overactive reward response that drives impulsivity and cravings for substances,” she told Healthline.

Still, GLP-1s may also exert anti-inflammatory effects on the central nervous system, reducing brain inflammation, which has been linked with depression and anxiety, Grawert said.

“As a result, semaglutide may help stabilize mood and improve emotional regulation by addressing these underlying biological processes in addition to its effects on metabolism,” she explained.

Looking at the implications for treating patients, Jason Kirby, Chief Medical Officer at Recovery Centers of America, said that GLP-1 medications could help people with metabolic and psychiatric disorders, possibly reducing hospitalizations and functional impairment associated with conditions like depression and anxiety. Kirby wasn’t involved in the study.

“However, this was an observational study, so it does not establish causality, and GLP-1 agents should not yet be considered primary treatments for depression or anxiety,” he told Healthline.

According to Kirby, these findings reinforce the importance of integrated care. He said the research represents “a promising avenue for future research at the intersection of psychiatry, addiction medicine, and metabolic health.”