Semaglutide and suicidal thoughts: a large health-record study

Why this study matters

Reports of suicidal thoughts in people taking semaglutide (Wegovy, Ozempic) led European regulators to open investigations. Suicidal ideation means thinking about ending one's life. Because this is such a serious question, researchers looked at a very large set of health records to see whether people on semaglutide had more of these recorded thoughts than people on other medicines. Canadian readers who have seen news coverage of this concern will want to know what the data showed and how much weight it can carry.

Who was in the study

The main analysis drew on 240618 people with overweight or obesity who were prescribed either semaglutide or a weight-management medicine that is not a GLP-1 medicine. The average age was 50.1 years, and 72.6% were female. To check the result, the researchers repeated the analysis in 1589855 people with type 2 diabetes (average age 57.5 years, 49.2% female), comparing semaglutide with non-GLP-1 diabetes medicines. According to the extracted data, the matched groups in the main analysis included 52783 people on each side. Follow-up was six months.

What the researchers did

This was a retrospective cohort study using the TriNetX Analytics Network, a large database of de-identified electronic health records from US health systems. Retrospective means the records already existed. No one was assigned to a medicine by chance.

The researchers used propensity score matching. This method pairs each person on semaglutide with a similar person on the comparison medicine, based on many recorded characteristics, so the two groups look alike on the things that were measured. They then compared the rate of two outcomes over six months: incident suicidal ideation (a first recorded episode in someone with no history of it) and recurrent suicidal ideation (a new episode in someone who had a previous record).

Results are given as hazard ratios. A hazard ratio compares how often an event happens in one group with another over time. A value of 1 means no difference, and a value below 1 means the event was less common in the semaglutide group.

What they found

In people with overweight or obesity, semaglutide was associated with a lower rate of new suicidal ideation than the comparison medicines: hazard ratio 0.27, with a 95% confidence interval of 0.20 to 0.36 (R32-C120). A confidence interval is the range in which the true value is likely to sit. According to the extracted data, new suicidal ideation was recorded in 0.11% of the semaglutide group and 0.43% of the comparison group.

For recurrent suicidal ideation, the hazard ratio was 0.44 (95% CI 0.32 to 0.60). The pattern was consistent across sex, age and ethnicity groups.

In the replication analysis in people with type 2 diabetes, the findings were similar. The summary we reviewed does not give the exact figures for that group.

The authors conclude that their findings do not support a higher risk of suicidal ideation with semaglutide compared with other weight-management or diabetes medicines.

Side effects and people who stopped

This study looked only at suicidal ideation. It does not report other side effects or how many people stopped their medicine.

What this study does not tell you

• This is an observational study. It cannot prove that semaglutide lowers the risk of suicidal thoughts, and the authors do not claim a protective effect. People who are prescribed semaglutide may differ from other patients in ways the records did not capture.
• The outcome depends on suicidal thoughts being recorded in a medical chart. Many people never tell a clinician, so the true rates are unknown.
• Follow-up was six months, so the study says nothing about longer use.
• The comparison was with other medicines, not with no treatment.
• The records came from US health systems, and the study did not include people from Canada.
• The PubMed abstract for this paper contains a garbled confidence interval for the main result. The interval on this page (0.20 to 0.36) was checked against the full published paper.
• The summary we reviewed does not state who funded the study.

What it means in Canada

This study is one of the largest to look at semaglutide and suicidal thoughts, and it did not find a higher recorded risk. It does not close the question, because health records miss many cases and the study was not a randomized trial. For how the medicine is used in Canada, see semaglutide in Canada. For coverage questions, see public drug coverage by province. If you or someone you know is thinking about suicide, please reach out to a health professional or a crisis service in your area.

Related reading

Other studies in this library that bear on the same question.

Source