A study led by researchers at Karolinska Institutet, Sweden, has found there is no association between glucagon-like peptide-1 receptor agonists (GLP1-RAs) and an increased risk of suicide and self-harm.
Last year, the European Medicines Agency (EMA) launched an investigation following around 150 reported possible cases of suicidal thoughts and self-injury with use of GLP-1 analogs. The investigation was completed in the spring and based on the limited data available at the time, it concluded that there were no obvious connections.
Researchers at Karolinska Institutet can now further support this conclusion after analysing large amounts of data from people treated with GLP-1 analogs in Sweden and Denmark .
"We found no clear link between the use of the drugs and an increased risk of suicide death, self-harm or depression and anxiety-related disorders. This is reassuring," said Dr Björn Pasternak, principal researcher at the Department of Medicine, Solna, Karolinska Institutet, and one of the study's lead authors.
The data includes approximately 300,000 adults aged 18–84 who started treatment with either GLP-1 analogs or SGLT2 inhibitors, from 2013 to 2021. In total, 124,517 adults initiated a GLP-1 receptor agonist and 174,036 initiated an SGLT2 inhibitor; among GLP-1 receptor agonist users.
During a mean (SD) follow-up of 2.5 (1.7) years, 77 suicide deaths occurred among users of GLP-1 receptor agonists and 71 suicide deaths occurred among users of SGLT2 inhibitors: weighted incidences were 0.23 vs 0.18 events per 1000 person-years (HR, 1.25; 95% CI, 0.83-1.88), with an absolute difference of 0.05 (95% CI, −0.03 to 0.16) events per 1000 person-years. The HR was 0.83 (95% CI, 0.70-0.97) for suicide death and nonfatal self-harm, and the HR was 1.01 (95% CI, 0.97-1.06) for incident depression and anxiety-related disorders.
Therefore, there was no apparent increase in the proportion of people who committed suicide, engaged in self-harm, or suffered from depression or anxiety-related disorders among users of GLP-1 receptor agonists.
"It is important to specifically examine people with previous self-harm or suicidal thoughts as they are at increased risk and it is possible that the drug's safety profile differs in this group," said Dr Peter Ueda, assistant professor at the same department and one of the study's main authors. However, he emphasised the importance of larger studies as more data is collected.
“In this binational cohort study including predominantly patients with type 2 diabetes, use of GLP-1 receptor agonists compared with SGLT2 inhibitors was not associated with an increased risk of suicide death, self-harm, or incident depression and anxiety-related disorders,” the authors concluded. “While reassuring, the study could not rule out smaller absolute risk differences for suicide death, and future studies with more outcome events should be performed as data accumulate.”
The findings were reported in the paper, ‘ GLP-1 receptor agonists and risk of suicide death: nationwide cohort study in Sweden and Denmark’, published in JAMA Internal Medicine. To access this paper, please click here
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