These two studies are good papers that are part of the arsenal dedicated to studying the 'worrisome' possible association between GLP-1 analogue drugs -mostly used in the treatment of type 2 diabetes and in some cases obesity-, and an increased tendency to suicide among users.

The study by Wadden et al. analyzes [the mental health of] subjects who participated in 4 clinical trials with semaglutide and liraglutide. To do so, they used the Patient Health Questionnaire (PHQ-9) and the Columbia Suicide Severity Rating Scale, perfectly validated for this type of study.

In the case of the work carried out by Ueda's group, the sample to be analyzed came from national patient registry data from Denmark and Sweden and they compared semaglutide with sodium-glucose cotransporter (SLGT2) inhibitors -both drugs widely used in the symptomatology of type 2 diabetes-. Neither study found differences between the groups treated with these drugs and their respective controls.

Their conclusions are well validated and, although reassuring, it is necessary to maintain continued vigilance to be able to assume, definitively, that there is no relationship between treatment with GLP-1 analogues and suicidal ideation or changes in mental health.

Currently, there are some cases reported by the FDA and the EMA that link suicidal ideation and treatment with GLP-1 analogues, but in no case has a cause-effect relationship been demonstrated. Evidence published throughout 2024 does not support a link between the two situations. In some cases it is attributed to a number of other comorbidities that are present in patients treated with GLP-1 analogues.

Therefore, these studies help us to broaden our knowledge in this field, although neither fully answers the question of whether these drugs are completely safe on our mental health.

These two studies have different limitations, among which we should highlight, firstly, in the study conducted by Wadden's team, the fact that patients with symptoms of mild depression and a history of major depression, schizophrenia or bipolar disorder in the two years prior to participation in the 4 clinical trials on which the study is based were excluded from the study. In addition, follow-up of most patients was limited to 68 weeks and there are patients who did not have type 2 diabetes. In the case of Ueda's team, their study does include patients with psychiatric disorders and a 5-year follow-up, although it was not taken into account whether the subjects dropped out of treatment. On the other hand, both studies were limited to evaluating only 2 GLP-1 analogues, semaglutide and liraglutide, and neither was compared with another GLP1/GIP receptor analogue, tirzepatide. Considering that there are a large number of marketed drugs with these characteristics, these two studies are limited.

In an overall analysis, these findings help to reassure users of these drugs regarding the suspicion raised by the major drug regulatory agencies, i.e. the EMA and the FDA, which linked their use to an increase in suicidal tendencies. At the same time, these results support most of the recently published studies that do not support this association. However, further research and vigilance in the prescription of GLP-1 analogues is needed, especially in patients who also suffer from psychiatric disorders.