Two glucagon-like peptide-1 (GLP-1) receptor agonists, semaglutide and – to a lesser extent – liraglutide, have been shown to be effective in reducing the risk of worsening mental illness in people who also have diabetes, a large Swedish study has found.
The study, which was published in The Lancet Psychiatry, used Swedish national health register data from 2009 to 2022, and included 95,490 people with depression or anxiety who were taking antidiabetic medications.
The researchers compared the GLP-1 drugs, semaglutide, liraglutide, exenatide and dulaglutide – alone and as a class – against periods of non-use and against other non-GLP-1 second-line diabetes medications. To minimise bias, they tracked the same patients across periods when they were on and off the medications.
Mental health deterioration was the study’s primary measure and encompassed psychiatric hospital admissions, extended sick leave, self-harm and suicide. Depression, anxiety, and substance use disorder were also examined separately as secondary outcomes.
GLP-1s and worsening mental illness
The researchers found that semaglutide was associated with a 42% lower risk of worsening mental illness, while liraglutide was linked to an 18% decreased risk. The authors asserted that this association did not appear to reflect an effect of the whole GLP-1 receptor agonist class as exenatide or dulaglutide did not elicit a similar risk reduction. Though the study acknowledges that the statistical power for exenatide and dulaglutide was low.
In relation to the study’s secondary outcomes, the data showed that semaglutide was linked to reduced risk of worsening depression, anxiety and substance use disorder. Meanwhile, liraglutide was associated only with reduced risk of worsening depression.
The authors concluded that semaglutide, and to a lesser degree liraglutide, may offer dual therapeutic benefits as treatment options for reducing the risk of worsening depression and anxiety, in addition to treating diabetes and obesity. Consequently, the authors called for randomised controlled trials to confirm these findings.
Type 2 diabetes affects more than 4.6 million people in the UK and research shows that those with the condition are about twice as likely to have depression as the wider population, and have a 41% higher risk of developing anxiety disorders as well.
In 2024, researchers found an apparent disproportional risk of suicidal thoughts with semaglutide compared with other diabetes drugs.
Yet earlier that year, the European Medicine Agency (EMA)’s Pharmacovigilance Risk Assessment Committee concluded that available evidence does not support a causal association between GLP-1 receptor agonists and suicidal and self-injurious thoughts and actions.
A version of this article was originally published by our sister publication The Pharmacist.
