New studies find no increased depression or suicidality with GLP-1 drugs

September 17, 2024

Two studies reported in JAMA Internal Medicine last week provide reassurance that GLP-1 medications such as Ozempic, Monjouro, Wegovy and Zepbound are not likely to lead to increased depression or suicidality. These complement a large observational study reported in January that showed those on these drugs for obesity had lower rates of suicidal ideation and suicide than those on other obesity medications. However, these new studies are stronger because one was a randomized clinical trial and the other included full national registries of medication use, medical care and death.

Depression scores among those on semaglutide compared to placebo

Source: Wadden, et al JAMA IM September 3, 2024. Higher PHQ-9 scores mean that the patient is more likely to be depressed. Scores of 10 represent moderate depression and 20 represent major depression; the maximum score is 27.

The first study followed over 2,000 patients treated with the highest recommended dose of Wegovy for between 17 and 24 months, and found that their PHQ-9 scores, a standard way to assess depression, were statistically significantly better than those of patients treated with placebo.

The second study retrospectively reviewed 72,420 with no history of psychiatric disease who were started on GLP-1 medications for diabetes between 2013 and 2021 in Sweden and Denmark. The researchers found that suicide rates and incidents of self-harm were not higher than the general population. About half of the patients in this research were on liraglutide (Saxenda or Victoza), an earlier daily GLP-1 medication which leads to less weight loss than semaglutide and tirzepatide, which are now much more commonly used for obesity.

In both instances, patients with preexisting mental illness were excluded, so these studies cannot rule out worsening of existing mental health problems from this class of drugs.

Implications for employers:

-       This is further evidence that this class of drugs, which leads to substantial weight loss in most with obesity and improves outcomes in people with obesity or diabetes, is generally safe as currently being prescribed.

-       GLP-1 costs are driving a substantial portion of the increase in pharmacy costs for employers that cover these drugs for obesity. Employers that do not cover these medications should not make this decision at this point based on concerns about suicidality.

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