Translation of a-t 2024; 55: 40

SUICIDAL TENDENCIES IN PATIENTS TREATED WITH GLP-1 AGONISTS – RISK SIGNAL NOT CURRENTLY CONFIRMED

In July 2023, the European Medicines Agency (EMA) reported that the European Pharmacovigilance Risk Assessment Committee (PRAC) was, at the request of the Icelandic Medicines Agency, investigating a risk signal for suicidal tendencies in connection with GLP-1 agonists such as liraglutide (SAXENDA, VICTOZA), and to do this was assessing 150 corresponding suspect notifications, among other things.¹ The result is now available: in the PRAC's opinion, the data that are currently available do not indicate a causal link between the use of the incretin mimetics and suicidal or self-harm-related thoughts or actions. ² In addition to spontaneous reports, the Committee also used two cohort studies^3,4 for its assessment.²

In a first investigation,³ electronic health data from the USA was used to compare the risk of suicidal thoughts in patients receiving semaglutide (OZEMPIC, WEGOVY) to treat obesity (n = 52,783) and type 2 diabetes (n = 27,276) with that in two control groups being treated with other anti-obesity or anti-diabetic drugs matched using propensity scores. The incidence of suicidal thoughts within six months of the start of treatment is significantly less in patients in both cohorts receiving semaglutide than it is in patients receiving alternative treatments (obesity: 0.11% compared to 0.43%, hazard ratio [HR] 0.27; 95% confidence interval [CI] 0.20-0.36; type 2 diabetes: 0.13% compared to 0.36%, HR 0.36; 95% CI 0.25-0.53). The risk of a relapse when taking the GLP-1 analogue is also lower in people with a history of known suicidal thoughts (HR 0.44 and 0.51; n = 865 and 251 per group, respectively).³

The second study carried out by the EMA² is currently only available as a study report.⁴ Based on electronic health data from Great Britain, the occurrence of suicidal tendencies or self-harm-related thoughts/actions in patients with type 2 diabetes using a GLP-1 agonist (n = 6,207) or an SGLT-2 inhibitor (n = 20,855; e.g. dapagliflozin [FORXIGA]) for the first time was determined. Within a median follow-up of 3.5 years and 2.0 years, 125 incidents of this type occurred in patients receiving incretin mimetics, as compared with 175 in patients receiving SGLT-2 inhibitors, corresponding to an adjusted incidence rate of 0.36 compared to 0.33 per 100 person-years. No statistically significant increase in risk can be deduced from this (adjusted HR 1.10; 95% CI 0.86-1.41). Various sensitivity analyses support the result.⁴ Following a PRAC meeting in November 2023, however, additional post-hoc analyses were carried out, one of which (a sub-group assessment of patients with obesity before the start of treatment) calculated a significant increase in risk (aHR 1.33; 95% CI 1.02-1.72). Overall, however, the authors (and evidently the PRAC²) consider that the results do not indicate a clinically relevant increased risk of suicidal or self-harm tendencies in patients treated with GLP-1 agonists compared to SGLT-2 inhibitors. However, further studies to confirm this are needed.⁴

The US Food and Drug Administration (FDA), which is currently also evaluating the risk of suicidal tendencies in patients being treated with GLP-1 agonists and unlike the EMA is also including tirzepatide* (MOUNJARO, a-t 2023; 54: 91-2 and 2024; 55: 29-30), does not yet consider there to be a link according to an interim analysis.⁵ We feel that increased awareness when prescribing incretin mimetics is currently still appropriate, –Ed.

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