Patients on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) - Victoza (Liraglutide 1.8mg), Saxenda (Liraglutide 3mg), Ozempic (Semaglutide 1mg) and Wegovy (Semaglutide 2.4mg) - exhibited a 195% higher risk of major depression, a 108% increased risk for anxiety and a 106% elevated risk for suicidal behaviour, according to a study led by researchers from Chung Shan Medical University, Taichung, Taiwan.
For this study, the researchers used post-marketing data to compare patients prescribed GLP-1 RAs (cases) with those not taking these medications (controls). The analysis spanned data from January 2015 to December 2023. To minimise selection bias, they employed 1:1 propensity score matching to account for demographic factors such as age, sex, race, and comorbidities. After matching, the study included 162,253 case and control patients.
After matching they noted that the mean age in the cohorts was 52.4 years, with the population comprising 55.6% females and 61% Whites. The prevalence of comorbidities was as follows: 51.1% of patients with hypertension, 50% with diabetes mellitus, 5.2% with psychoactive substance use and 0.5% experiencing problems related to housing and economic circumstances.
Outcomes
From six months to five years, the researchers found that there was a consistent increase in psychiatric outcomes among GLP-1 RA users. At six months, the incidence in the GLP-1 RA group was 9.36%, compared to 4.76% in the non-GLP-1 RA group. This trend continued at one year (15.29% vs. 7.63%), three years (29.62% vs. 16.45%) and five years (39.64% vs. 23.38%). The incidences of major depressive disorder, anxiety, and suicidal ideations or attempts, as well as their hazard ratios, are higher in the GLP-1 RA group, indicating an association with GLP-1 RA treatment over time.
The hazard ratio (HR) for any psychiatric disease is 1.98 (95% CI 1.94–2.01). Specifically, the HR for major depressive disorder is 2.95 (95% CI 2.82–3.08), for anxiety 2.08 (95% CI 2.04–2.12) and for suicidal ideations or attempts 2.06 (95% CI 1.92–2.21), further demonstrating the significant association with GLP-1 RA treatment over time.
“It is important to mention that the follow-up duration of Wegovy is only three years, whereas other GLP-1 RA medications were studied for five years,” the researchers noted. “The most striking result is the suicidal ideations or attempts of the Ozempic group, which showed an approximately 2.4-fold increase in risk. These findings suggest varied psychiatric risks associated with different GLP-1 RA medications, with Wegovy demonstrating the highest risk for conditions such as major depressive disorder and anxiety.”
Across all demographic subgroups, GLP-1 RA users consistently exhibited an elevated risk of psychiatric diseases. For example:
Female users had a 105% higher risk of any psychiatric disease (HR: 2.05, 95% CI 2.01–2.09) compared to non-users.
Patients aged 18–49, 50–69 and ≥70 showed increased risks of 101%, 78%, and 71%, respectively, for any psychiatric disease when using GLP-1 RAs compared to non-users.
The risk of major depressive disorder was the highest among female GLP-1 RA users, with a 216% elevated risk (HR: 3.16, 95% CI 2.98–3.34) compared to non-users, surpassing the risks of anxiety and suicidal ideations or attempts.
Among racial groups, Black faced the highest risk of anxiety, with a 137% elevated risk (HR: 2.37, 95% CI 2.25–2.50) compared to non-users.
These findings underscore the consistent relationship between psychiatric outcomes and GLP-1 RA usage, with a particular focus on the heightened risks for females, age, sex and race.
The HR for any psychiatric disease in the Victoza group was 1.65 (95% CI 1.59–1.72), while in the Saxenda group, it was 1.73 (95% CI 1.64–1.83). The Ozempic group showed an HR of 1.72 (95% CI 1.67–1.76) and the Wegovy group presented a significantly higher HR of 2.14 (95% CI 2.05–2.24).
“These findings underscore the critical need for physicians to thoroughly assess patient history before prescribing GLP-1 RAs and highlight the urgent requirement for further prospective clinical trials to fully understand the implications of GLP-1 RA use on mental health in the obese patient population,” the authors concluded.
The findings were reported in the paper, ‘The risk of depression, anxiety, and suicidal behavior in patients with obesity on glucagon like peptide-1 receptor agonist therapy’, published in Scientific Reports. To access this paper, please click here
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