GLP-1 Evidence

Not medical advice. A record of published research and our assessments of it. The limits

Association of semaglutide with risk of suicidal ideation in a real-world cohort

Design
Retrospective cohort · 240618 participants · Hard outcome
Match to healthy normal-weight adults aged 55–75
Different populationEHR cohorts with obesity or diabetes; younger than target.
Could weight loss explain it?
UnknownSafety outcome.
Study tier
Study tier 3Large propensity-matched EHR cohort; observational; short follow-up.
Assessment
Version 2 · curated · Sep 13, 2026

Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.

In 240,618 US patients with overweight or obesity, semaglutide was associated with lower, not higher, rates of suicidal thoughts compared with other weight-loss drugs over six months. Publicly funded; does not support the suicidality concern.

01Findings

What the study reported

Drugs
Semaglutide
Comparator
non-GLP-1 anti-obesity or antidiabetic medications
Primary outcome
Incident and recurrent suicidal ideation over 6 months
Effect
Incident HR 0.27; recurrent HR 0.44 (obesity cohort); replicated in T2D
95% confidence interval
0.32 to 0.60 (recurrent)
Follow-up
6 months
Adverse events
Not extracted
Limitations
Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.

Who was studied

Mean age
50.1
Sex distribution
72.6% female
Obesity status
overweight/obesity cohort; T2D replication cohort
Diabetes status
separate cohorts
Sample size
240618

Study quality details

Study design
Retrospective cohort
Sample size
240618
Randomization
no
Blinding
not stated
Comparator
not stated
Follow up duration
50.1 years
Outcome type
unknown
Replication
not assessed (auto)
Consistency with other evidence
not assessed (auto)
Population applicability
INDIRECT
Statistical precision
large cohort
Risk of bias
EHR diagnosis codes; residual confounding; short follow-up
Funding conflicts
no
Peer review status
yes
02Funding

Funding and conflicts

Funding
NIH (NIA, NIAAA, NICHD, NCI)
Industry funded
No
Manufacturer
None identified
Sponsor role
Independent.
Author conflicts
Authors declare no competing interests.
Independent replication
yes (Nordic registers, PMID 39226030)

Funding is shown on every study and never used to score it.

03Claims

Claims this study bears on

04Source

The source, as retrieved

Abstract

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.

Where this record came from

SourceRetrievedIdentifier
pubmedSep 13, 202638182782
first ingestion