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Association of semaglutide with risk of suicidal ideation in a real-world cohort
Open accessAbstract
Concerns over reports of suicidal ideation associated with semaglutide treatment, a glucagon-like peptide 1 receptor (GLP1R) agonist medication for type 2 diabetes (T2DM) and obesity, has led to investigations by European regulatory agencies. In this retrospective cohort study of electronic health records from the TriNetX Analytics Network, we aimed to assess the associations of semaglutide with suicidal ideation compared to non-GLP1R agonist anti-obesity or anti-diabetes medications. The hazard ratios (HRs) and 95% confidence intervals (CIs) of incident and recurrent suicidal ideation were calculated for the 6-month follow-up by comparing propensity score-matched patient groups. The study population included 240,618 patients with overweight or obesity who were prescribed semaglutide or non-GLP1R agonist anti-obesity medications, with the findings replicated in 1,589,855 patients with T2DM. In patients with overweight or obesity (mean age 50.1 years, 72.6% female), semaglutide compared with non-GLP1R agonist anti-obesity medications was associated with lower risk for incident (HR = 0.27, 95% CI = 0.200.32-0.600.36) and recurrent (HR = 0.44, 95% CI = 0.32-0.60) suicidal ideation, consistent across sex, age and ethnicity stratification. Similar findings were replicated in patients with T2DM (mean age 57.5 years, 49.2% female). Our findings do not support higher risks of suicidal ideation with semaglutide compared with non-GLP1R agonist anti-obesity or anti-diabetes medications.
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“in the retrospective cohort study using TriNetX Analytics Network electronic health records, semaglutide significantly lowered the risk of both new (HR, 0.27; 95% CI, 0.20 to 0.32) and recurrent (HR, 0.44; 95% CI, 0.32 to 0.60) suicidal ideation compared to non-GLP-1 RAs anti-obesity treatments [80].”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [80]
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“whereas several observational studies have generated varied findings on of the effect of GLP-1 receptor agonists on the risk of suicidal ideation, self-harm, and suicide, which may be a result of methodological limitations in these studies.8 9 10 11 12 13”
From Glucagon-like peptide-1 receptor agonists and risk of suicidality among patients with type 2 diabetes: active comparator, new user cohort study (2025) · cites this paper as [9]
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“and recurrent (HR, 0.44; 95% CI, 0.32 to 0.60) suicidal ideation compared to non-GLP-1 RAs anti-obesity treatments [80].”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [80]
In the citing paper
“Among AOMs currently approved, tirzepatide 15 mg and semaglutide 2.4mg have the greatest efficacy (Figure 1).65,67,87”
From Approach to Obesity Treatment in Primary Care: A Review (2024) · cites this paper as [87]
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Metadata
- Authors
- Wang, W., Volkow, N. D., Berger, N. A., Davis, P. B., Kaelber, D. C., & Xu, R.
- Affiliations
- Case Western Reserve University (US)
- National Institutes of Health (US)
- MetroHealth (US)
- Corresponding author
- Volkow, Nora D.
- Xu, Rong
- Venue
- Nature Medicine
- Published
- 2024-01
- Volume
- 30
- Issue
- 1
- Pages
- 168-176
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC11034947
- OpenAlex
- W4390616108
- Cited by
- 248
- References
- 34
- Citations by year
- 2026: 72 · 2025: 91 · 2024: 84
- FWCI
- 81.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Case Comprehensive Cancer Center, Case Western Reserve University (CA043703)
- National Institute on Alcohol Abuse and Alcoholism (R01AA029831)
- National Institute on Aging (R01AG061388, R56AG062272, RF1AG076649, R01AG057557)
- National Cancer Institute (CA043703, CA2332216, P30CA043703, R25CA221718)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (DP2HD084068)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Keywords
- semaglutide, suicidal ideation, GLP-1 receptor agonists, type 2 diabetes, obesity, anti-obesity drugs, drug safety, adverse drug reactions, real-world evidence
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide, Diabetes Mellitus, Type 2, Glucagon-Like Peptides, Female, Humans, Hypoglycemic Agents, Male, Middle Aged, Obesity, Retrospective Studies, Anti-Obesity Agents, Overweight, Suicidal Ideation
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