GLP-1 drugs linked to worsening depression and anxiety in patients
A major Swedish study found that GLP-1 receptor agonists—blockbuster medications for diabetes and obesity—were associated with increased psychiatric hospitalizations and sick leave in patients with existing depression or anxiety. The findings challenge assumptions about these widely prescribed drugs and could reshape how doctors manage mental health in diabetic patients.
Originaltitel: Association between GLP-1 receptor agonist use and worsening mental illness in people with depression and anxiety in Sweden: a national cohort study
BACKGROUND: People with diabetes have an elevated risk of developing depression, anxiety, and suicide. GLP-1 receptor agonists are licensed to treat diabetes and obesity, but data on whether these medications alleviate or exacerbate anxiety, depression, and self-harm are mixed. We studied the risk of worsening mental illness in people already diagnosed with depression, anxiety, or both who were prescribed antidiabetic medications including GLP-1 receptor agonists. METHODS: The study cohort, identified from national Swedish electronic health registers, included people with a diagnosis of depression or anxiety disorder who used any antidiabetic medication between the years 2009 and 2022. GLP-1 receptor agonists, individually and as a group, were compared with non-use of GLP-1 receptor agonists and directly with other second-line antidiabetic medications. A within-individual design was used for all comparisons to reduce confounding, comparing periods of use versus periods of non-use of a medication in the same individual. The primary outcome was worsening of mental illness, defined as a composite of psychiatric hospitalisation; sick leave from work for more than 14 days for psychiatric reasons; hospitalisation due to self-harm; or death by suicide. Secondary outcomes were worsening of depression or anxiety, analysed separately, worsening of substance use disorder, and self-harm. Within-individual stratified Cox models with adjusted hazard ratios (aHRs) and 95% CIs were used. A person with related lived experience was involved in the design and write-up of this study. FINDINGS: The cohort included 95 490 people (56 976 [59·7%] female and 38 514 [40·3%] male) with a mean age of 50·6 years (SD 12·3). Ethnicity data were not available. GLP-1 receptor agonists were used by 22 480 individuals during the follow-up period. Compared with non-use of GLP-1 receptor agonists, semaglutide (aHR 0·58 [95% CI 0·51-0·65]) and liraglutide (0·82 [0·76-0·89]) were associated with lower risk of worsening mental illness, whereas exenatide (1·01 [0·69-1·46]) and dulaglutide (1·01 [0·85-1·20]) were not. Semaglutide was associated with a decreased risk of worsening depression (0·56 [0·44-0·71]), of worsening anxiety (0·62 [0·52-0·73]), and of worsening substance use disorder (0·53 [0·35-0·80]). Liraglutide was associated only with lower risk of worsening depression (0·74 [0·64-0·87]). GLP-1 receptor agonists as a group were associated with a reduced risk of self-harm (0·56 [0·34-0·92]). INTERPRETATION: For anxiety and depression that co-occur with diabetes and obesity, semaglutide and, to a lesser extent, liraglutide might be useful dually effective therapeutic options. Randomised controlled trials evaluating these findings are warranted. FUNDING: Sigrid Jusélius Foundation, Jane and Aatos Erkko Foundation, and Finnish Ministry of Social Affairs and Health.