Semaglutide was associated with a 42% lower risk of worsening mental illness among patients with depression or anxiety receiving noninsulin antidiabetic therapy, compared with periods of nonuse, in a national cohort study from Sweden.
Researchers analyzed 95,490 patients with diagnosed depression or anxiety who received noninsulin antidiabetic medications between 2009 and 2022 in a study published in The Lancet Psychiatry. Using a within-patient design, periods of glucagon-like peptide-1 receptor agonist (GLP-1 RA) use were compared with nonuse within the same patient to reduce confounding.
The primary outcome—a composite of psychiatric hospitalization, sick leave lasting more than 14 days for psychiatric reasons, hospitalization for self-harm, or suicide—occurred in 32,638 patients over a mean follow-up of 5.2 years. Semaglutide was associated with a lower risk of this outcome, while liraglutide was associated with a more modest reduction. Exenatide and dulaglutide were not associated with a difference in risk.
Secondary analyses showed semaglutide was associated with lower risk of worsening depression, anxiety, and substance use disorder. Liraglutide was associated only with a reduced risk of worsening depression. At the class level, GLP-1 receptor agonists were associated with a lower risk of self-harm.
In comparisons using empagliflozin as the reference treatment, semaglutide was associated with a lower risk of worsening mental illness, while dapagliflozin and sitagliptin were associated with higher risk.
The study population had a mean age of 50.6 years, and 59.7% were female. Among participants, 81.5% had anxiety disorders, 54.9% had depression, and 36.4% had both. GLP-1 receptor agonists were used by 23.5% of the cohort.
Results were similar after excluding the first 30 and 60 days of exposure and when analyses were limited to periods following semaglutide approval.
The researchers noted that the within-patient design reduced confounding by comparing periods of use and nonuse in the same patient, but causality cannot be established. Additional limitations included lack of data on symptom severity, body mass index, and glycemic control, as well as limited statistical power for less frequently used agents.
“Semaglutide and, to a lesser extent, liraglutide were associated with significantly lower risk of worsening mental illness,” wrote lead study researcher Heidi Taipale, PhD, of the University of Eastern Finland and Niuvanniemi Hospital, and colleagues.
Full disclosures are available in the study.
Source: The Lancet Psychiatry
