Swedish cohort ties semaglutide to lower risk of worsening mental illness
Registry data from Sweden associate semaglutide with fewer psychiatric crises in people who already have depression or anxiety, though the observational design cannot prove the drug is responsible.
Swedish national health registers show that people with depression or anxiety were less likely to see their psychiatric condition worsen while taking semaglutide than while not taking it, according to a cohort study published in The Lancet Psychiatry [1][2].
The analysis followed 95,490 people who had a recorded diagnosis of depression, anxiety, or both and who used any antidiabetic medication between 2009 and 2022 [1][2]. Women made up 59.7% of the cohort (56,976 people) and men 40.3% (38,514 people); the mean age was 50.6 years (SD 12.3) [2]. The registers did not contain information on ethnicity [2]. During follow-up, 22,480 of the participants used a GLP-1 receptor agonist [2].
Each person was compared with themselves: the researchers contrasted periods when someone was filling prescriptions for a given drug with periods when that same person was not, a within-individual design intended to reduce confounding [2]. The main outcome combined four events — psychiatric hospital admission, psychiatric sick leave lasting more than 14 days, hospital admission for self-harm, and death by suicide [2]. Estimates came from within-individual stratified Cox models, reported as adjusted hazard ratios with 95% confidence intervals [2].
For the combined outcome, semaglutide carried an adjusted hazard ratio of 0.58 (95% CI 0.51–0.65) and liraglutide 0.82 (0.76–0.89), both below 1.0 [2]. Exenatide (1.01, 0.69–1.46) and dulaglutide (1.01, 0.85–1.20) did not show a link in either direction [2].
The study also separated out individual outcomes. Semaglutide was associated with lower risk of worsening depression (0.56, 0.44–0.71), worsening anxiety (0.62, 0.52–0.73), and worsening substance use disorder (0.53, 0.35–0.80). For liraglutide, the only separate outcome with an association was worsening depression (0.74, 0.64–0.87). Pooled across the drug class, GLP-1 receptor agonists were associated with reduced risk of self-harm (0.56, 0.34–0.92) [2].
Semaglutide is the active molecule in Ozempic, Wegovy, and Rybelsus; liraglutide is the molecule in Victoza and Saxenda. Everyone in the cohort was taking these medicines as diabetes treatment, not for weight loss [2]. Tirzepatide, sold as Mounjaro and Zepbound, does not appear among the drugs reported on, and the study does not explain why [2].
The authors write that for anxiety and depression that overlap with diabetes and obesity, semaglutide and, to a lesser degree, liraglutide "might be useful dually effective therapeutic options," and that randomized controlled trials testing the findings are warranted [2]. Funding came from the Sigrid Jusélius Foundation, the Jane and Aatos Erkko Foundation, and the Finnish Ministry of Social Affairs and Health [2]. Three authors reported research grants from Janssen paid to their institutions, and several reported personal fees, consulting work, or honoraria from companies including Lundbeck, Otsuka, Janssen, Orion, and Recordati; one author declared no competing interests [2]. A person with related lived experience contributed to the study's design and write-up [2].
Why it matters for patients
Depression and anxiety are common alongside type 2 diabetes, and earlier research on whether GLP-1 drugs help or hurt mood has pointed in both directions [2]. By comparing the same individuals over time rather than two different groups of patients, this analysis removes some sources of distortion, but it still cannot show that the medication caused the difference in outcomes [2].
What the data indicate is narrower than a claim about mood improvement: in this cohort, psychiatric crises were less frequent during semaglutide use. Whether that pattern should influence anyone's prescription is a conversation for a clinician, and the results are not a reason to start, stop, or alter a medication on one's own.
What is not yet known
No one in the study was free of a psychiatric diagnosis at the start, so the results say nothing about prevention [2]. Because the cohort was defined by antidiabetic treatment, it is not known whether the same pattern would hold in people using semaglutide only for weight loss [2]. The abstract does not describe doses, so whether the association changes with dose has not been reported. And the study cannot establish cause and effect, which is why the authors call for randomized trials [2].
Sources
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