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Suicide and Self-Harm Events With GLP-1 Receptor Agonists in Adults With Diabetes or Obesity: A Systematic Review and
Pouya Ebrahimi1, Juan Carlos Batlle2, Aryan Ayati1
1Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Importance:
Bariatric surgery, once the criterion standard in obesity treatment, has a small but concerning association with increased suicidality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), originally developed to treat diabetes, now provide substantial efficacy in the treatment of obesity. However, concerns of risk of suicidality with these medicines have been raised.
Objective:
To evaluate the risk of suicidality and self-harm in randomized, placebo-controlled trials of GLP-1 RAs in adults with diabetes or obesity.
Data Sources:
MEDLINE, Embase, ClinicalTrials.gov, and Cochrane databases were systematically searched from inception to August 29, 2023.
Study Selection:
Reports of randomized clinical trials (RCTs) lasting 6 or more months comparing GLP-1 RAs with placebo for the treatment of diabetes or obesity published in peer-reviewed journals were identified. Two independent reviewers screened all search-identified studies for inclusion. Records of outcomes were queried from primary papers, ClinicalTrials.gov entries, and corresponding authors.
Data Extraction And Synthesis:
Two independent researchers abstracted data and assessed data quality and validity using PRISMA guidelines. Data were pooled using random-effects models.
Main Outcomes And Measures:
Pooled incidence of completed or attempted suicide, occurrences of suicidal ideation, or self-harm.
Results:
A total of 27 of 144 RCTs meeting inclusion criteria systematically recorded suicide and/or self-harm-related events and included 32 354 individuals receiving GLP-1 RAs and 27 042 treated with placebo, over 69 653 and 63 853 person-years of exposure, respectively. Event incidence was very low in the GLP-1 RA (0.047 per 100 person-years) and placebo (0.042 per 100 person-years) groups, with no statistically significant difference (rate ratio [RR], 0.76; 95% CI, 0.48-1.21; P = .25). Subgroup analyses did not suggest differences in outcomes based on diabetes status or GLP-1 RA used. Five studies were considered at risk of bias due to the loss of more than 5% of participants to follow-up. Otherwise, studies were not found to be heterogeneous nor at high risk of bias.
Conclusions And Relevance:
There is unlikely to be an increase in the very low incidence of suicide-related adverse events among individuals receiving GLP-1 RAs within the context of RCTs. While these findings may further ease concerns about these adverse effects, continued monitoring is warranted to identify particular patients who may be at risk as extended use of GLP-1 RAs expands.
Insights
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) show no increased risk of suicidality compared to placebo in randomized trials for obesity or diabetes. Event rates were very low in both groups, easing concerns about these widely used medications.
Area of Science:
- Pharmacovigilance and Clinical Trial Analysis
- Endocrinology and Metabolic Diseases
- Psychiatry and Behavioral Sciences
Background:
- Bariatric surgery, a standard obesity treatment, has a noted association with increased suicidality.
- Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are effective for diabetes and obesity but raise concerns about suicidality risk.
Purpose of the Study:
- To systematically evaluate the risk of suicidality and self-harm associated with GLP-1 RAs.
- To analyze data from randomized, placebo-controlled trials (RCTs) involving adults with diabetes or obesity.
Main Methods:
- Systematic search of MEDLINE, Embase, ClinicalTrials.gov, and Cochrane databases up to August 29, 2023.
- Inclusion of RCTs (≥6 months) comparing GLP-1 RAs with placebo in diabetes or obesity.
- Data extraction and quality assessment using PRISMA guidelines, with pooled analysis via random-effects models.
Main Results:
- 27 RCTs (32,357 on GLP-1 RAs, 27,046 on placebo) were analyzed.
- Incidence of suicide-related events was very low and statistically similar between GLP-1 RA (0.044/100 person-years) and placebo (0.040/100 person-years) groups (RR, 0.76; P=.24).
- Subgroup analyses showed no significant differences based on diabetes status or specific GLP-1 RA used; most studies had low risk of bias.
Conclusions:
- The incidence of suicide-related adverse events with GLP-1 RAs in RCTs is unlikely to be increased.
- Findings may alleviate concerns regarding suicidality risk with GLP-1 RAs.
- Continued post-market surveillance is recommended to monitor for potential risks in specific patient populations as GLP-1 RA use expands.
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