GLP-1 receptor agonists are widely used to treat type 2 diabetes and obesity. But in recent years, questions have been raised about whether these medications might worsen depression, anxiety, or even increase the risk of self-harm. A large national study published in The Lancet Psychiatry examined this issue closely—and the findings may be reassuring for patients and clinicians alike.
Researchers in Sweden studied nearly 100,000 people with diabetes who already had depression or anxiety. They found that some GLP-1 medications, especially semaglutide, were linked to a lower risk of worsening mental illness, not a higher one.
Why Mental Health and Diabetes Are Closely Connected
People with diabetes are more likely than the general population to develop depression and anxiety. These conditions can make blood sugar control more difficult, and poor metabolic control can worsen mood symptoms. This creates a cycle in which physical and mental health affect each other.
GLP-1 receptor agonists help regulate blood sugar and reduce appetite. Some studies have suggested they might improve mood, while others raised concerns about possible psychiatric side effects. Because results have been mixed, researchers wanted to examine the issue using a strong study design that reduces bias.
How the Study Was Designed
This was a national cohort study using Swedish health registers from 2009 to 2022. The study included:
- 95,490 people with a diagnosis of depression or anxiety
- All were using non-insulin antidiabetic medications
- 22,480 people used a GLP-1 receptor agonist during follow-up
The average age was about 50 years, and about 60% of participants were women.
To reduce bias, researchers used a within-individual design. This means each person served as their own comparison. Periods when someone was taking a GLP-1 drug were compared with periods when that same person was not taking one. This helps control for differences in baseline mental health severity and other personal characteristics. However, since the time they were not taking GLP-1 drugs happened first, there could also have been improvement in mental health over time, but with this research design, that is hard to tell.
The primary outcome was “worsening mental illness,” defined as:
- Psychiatric hospitalization
- Sick leave longer than 14 days for psychiatric reasons
- Hospitalization due to self-harm
- Death by suicide
Secondary outcomes included worsening depression, worsening anxiety, substance use disorder, and self-harm.
What the Researchers Found
The results showed clear differences between specific GLP-1 medications.
Semaglutide Had the Strongest Protective Association
Compared to periods when people were not using GLP-1 drugs, semaglutide use was associated with:
- 42% lower risk of worsening mental illness (adjusted hazard ratio 0.58)
- Lower risk of worsening depression
- Lower risk of worsening anxiety
- Lower risk of substance use disorder
Even when the analysis was restricted to hospital admissions only, semaglutide was still associated with reduced risk.
Liraglutide Also Showed Benefits
Liraglutide was linked to:
- An 18% lower risk of worsening mental illness
- Lower risk of worsening depression
- Reduced risk of psychiatric sick leave
However, its benefits were not as broad as semaglutide’s.
Not All GLP-1 Drugs Showed the Same Effect
Exenatide and dulaglutide were not associated with reduced risk of worsening mental illness.
This suggests the findings are not simply a “class effect” of all GLP-1 drugs. Instead, individual medications may differ.
Reduced Risk of Self-Harm
When GLP-1 drugs were analyzed as a group, they were associated with a lower risk of self-harm. Only one suicide occurred during GLP-1 use, and suicide deaths made up just 0.2% of the main outcome events.
Comparison With Other Diabetes Medications
To make sure results were not simply related to diabetes severity, researchers compared GLP-1 drugs with other common second-line diabetes medications, including:
- Empagliflozin
- Dapagliflozin
- Sitagliptin
Semaglutide was associated with a lower risk of worsening mental illness even when compared directly with empagliflozin. In contrast, dapagliflozin and sitagliptin were linked to higher risks compared to empagliflozin.
These comparisons strengthen the conclusion that semaglutide’s association with improved psychiatric outcomes is not just due to general diabetes treatment.
Why Might GLP-1 Drugs Affect Mood?
The authors discuss several possible biological explanations:
- GLP-1 signaling may reduce inflammation in the brain.
- It may influence serotonin and dopamine pathways involved in mood regulation.
- GLP-1 activation may support neuronal survival and reduce oxidative stress.
- Weight loss and improved metabolic control could indirectly improve mood.
However, the study does not prove that weight loss directly caused mental health improvement. The relationship is likely complex.
Important Limitations
Because this was an observational study, it cannot prove causation. Other limitations include:
- No direct measures of symptom severity
- No data on body weight or HbA1c changes
- Limited statistical power for some drugs
- Results based on the Swedish healthcare system
- The results do not control for what could have happened over time
Still, the large sample size and within-individual design make the findings strong and meaningful.
What This Means for Patients and Clinicians
This study provides reassurance that GLP-1 receptor agonists—especially semaglutide—are not linked to worsening depression or anxiety in people who already have these conditions. In fact, they may be associated with improved outcomes.
The authors suggest that randomized controlled trials are now needed to confirm whether GLP-1 drugs could play a dual role in treating both metabolic and mental health conditions.
For patients living with diabetes and depression or anxiety, these findings are encouraging. Rather than increasing psychiatric risk, certain GLP-1 medications may offer additional mental health benefits.
Source
Taipale H, Taylor M, Lähteenvuo M, Mittendorfer-Rutz E, Tanskanen A, Tiihonen J. Association between GLP-1 receptor agonist use and worsening mental illness in people with depression and anxiety in Sweden: a national cohort study. Lancet Psychiatry. 2026;13:327–335.
Accessed by: https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(26)00014-3/fulltext
