Real world study provided reassurance of the safety of GLP-1 therapy on mental health and suicide risk

In July of 2023, the European Medicines Agency announced that it was conducting a formal review into reports that the use of these drugs could increase the risk for suicide and suicidal thoughts. This was based on The Icelandic Medicines Agency receiving reports of up to 150 people who took the drugs and experienced suicidal thoughts or self-injury.

This was surprising since there was no signal of this potential adverse effect in the randomized trial data. However, since randomized trials have strict inclusion criteria to exclude people with psychological issues at baseline, trial safety data may not observe concerns about psychiatric safety risks.

As such, the other approach is to look at real world data. To this end, a study published in JAMA medicine have reported this.¹

In the study, investigators identified everyone in Sweden and Denmark who started taking semaglutide or liraglutide (N = 124 517) for diabetes from 2013 to 2021. Use of SGLT2 inhibitor (N = 174 036) at the same time but not GLP-1 therapy was used as a control group.

In any case, 124 517 adults were prescribed Ozempic or an Ozempic-like drug, and 174 036 started taking an SGLT2 inhibitor. Interestingly, those who were prescribed Ozempic were more likely to be using or to have previously used antidepressants and to have had an outpatient visit for a psychiatric diagnosis. Analysis was undertaken via a propensity score analysis to adjust for confounders. The study showed that 77 new Ozempic users died from suicide (6 out of 10 000 people) as did 71 new SGLT2 inhibitor users (4 out of 10 000 people). While there was a slight increase risk with GLP-1, the margin of error is very large. Crucially, when death from suicide and nonfatal self-harm were combined, GLP-1 receptor agonists appear to be protective (HR, 0.83; 95% CI, 0.07–0.97), while no difference was noted between GLP-1 and SGLT2 inhibitor on new psychiatric disorder.

In my opinion therefore, the outcome is equivocal and that there is no significant association between Ozempic and suicide. These findings are reassuring but further monitoring and surveillance is needed to monitor its safety.