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Comment
. 2024 Nov 1;184(11):1301-1312.
doi: 10.1001/jamainternmed.2024.4369.

GLP-1 Receptor Agonist Use and Risk of Suicide Death

Peter Ueda  1 , Jonas Söderling  1 , Viktor Wintzell  1 , Henrik Svanström  1   2 , Laura Pazzagli  1 , Björn Eliasson  3   4 , Mads Melbye  5   6   7   8 , Anders Hviid  2   9 , Björn Pasternak  1   2
Affiliations
Comment

GLP-1 Receptor Agonist Use and Risk of Suicide Death

Peter Ueda et al. JAMA Intern Med. .

Erratum in

  • Error in Figure 1.
    [No authors listed] [No authors listed] JAMA Intern Med. 2024 Nov 1;184(11):1396. doi: 10.1001/jamainternmed.2024.6163. JAMA Intern Med. 2024. PMID: 39495245 Free PMC article. No abstract available.

Abstract

Importance: Concerns have been raised regarding a link between use of glucagon-like peptide-1 (GLP-1) receptor agonists and increased risk of suicidality and self-harm.

Objective: To assess the association between use of GLP-1 receptor agonists and the risk of suicide death in routine clinical practice.

Design, setting, and participants: This active-comparator new-user cohort study used nationwide register data from Sweden and Denmark from 2013 to 2021. Adults 18 to 84 years old who initiated treatment with GLP-1 receptor agonists or the comparator sodium-glucose cotransporter-2 (SGLT2) inhibitors were included. Data were analyzed from March to June 2024.

Exposure: Initiation of treatment with a GLP-1 receptor agonist or SGLT2 inhibitor.

Main outcomes and measures: The primary outcome was suicide death recorded in the cause of death registers. Secondary outcomes were the composite of suicide death and nonfatal self-harm and the composite of incident depression and anxiety-related disorders. Using propensity score weighting, hazard ratios (HRs) with 95% CIs were calculated separately in the 2 countries and pooled in a meta-analysis.

Results: In total, 124 517 adults initiated a GLP-1 receptor agonist and 174 036 initiated an SGLT2 inhibitor; among GLP-1 receptor agonist users, the mean (SD) age was 60 (13) years, and 45% were women. During a mean (SD) follow-up of 2.5 (1.7) years, 77 suicide deaths occurred among users of GLP-1 receptor agonists and 71 suicide deaths occurred among users of SGLT2 inhibitors: weighted incidences were 0.23 vs 0.18 events per 1000 person-years (HR, 1.25; 95% CI, 0.83-1.88), with an absolute difference of 0.05 (95% CI, -0.03 to 0.16) events per 1000 person-years. The HR was 0.83 (95% CI, 0.70-0.97) for suicide death and nonfatal self-harm, and the HR was 1.01 (95% CI, 0.97-1.06) for incident depression and anxiety-related disorders.

Conclusions and relevance: This cohort study, including mostly patients with type 2 diabetes, does not show an association between use of GLP-1 receptor agonists and an increased risk of suicide death, self-harm, or incident depression and anxiety-related disorders. Suicide death among GLP-1 receptor agonist users was rare, and the upper limit of the confidence interval was compatible with an absolute risk increase of no more than 0.16 events per 1000 person-years.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Ueda reported grants from the Karolinska Institutet and the Strategic Research Area Epidemiology program during the conduct of the study. Dr Svanström reported being a former employee of IQVIA. Dr Pazzagli was supported by a grant from the Swedish Research Council for Health, Working Life, and Welfare. Dr Eliasson reported support from Konung Gustaf V:s and Drottning Victorias Frimurarstiftelse and personal fees from Novo Nordisk, Sanofi, Eli Lilly, Amgen, AstraZeneca, Boehringer Ingelheim, and Abbott outside the submitted work. Dr Melbye was supported by a grant from the Danish Cancer Society. Dr Hviid reported grants from the Novo Nordisk Foundation, the Lundbeck Foundation, and the Denmark Independent Research Fund outside the submitted work. Dr Pasternak reported grants from the Karolinska Institutet during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of the Study Cohort for the Primary Outcome Analysis
GLP-1 indicates glucagon-like peptide-1; SGLT2, sodium-glucose cotransporter-2.
Figure 2.
Figure 2.. Weighted Cumulative Incidence for Suicide Death Among Users of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors in Sweden and Denmark
Standardized mortality ratio weighting using a propensity score.
See this image and copyright information in PMC

Comment on

References

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