Type 2 diabetes is a disease where the body cannot properly regulate blood sugar levels. People with diabetes are at higher risk for many diseases, including depression. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a type of medication used to treat type 2 diabetes. GLP-1 RAs may potentially increase the risk of suicide and self-harm, but few studies have been conducted on this association. To address this question, we will use the Clinical Practice Research Datalink to conduct a large cohort study to determine whether the use of GLP-1 RAs is associated with an increased risk of suicide, suicidal ideation, or self-harm. The findings of this study could have important implications for prescribing practices for patients with type 2 diabetes.
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a second- to third-line treatment for type 2 diabetes that exerts its effects through GLP-1 signalling. Several case reports indicate that GLP-1 RAs may increase the risk of suicide and self-harm, which has prompted investigation by several regulatory agencies. Observational studies on the topic are scarce and have been subject to several limitations, and stronger evidence on the association is needed.
Our study will explore the relationship between the use of GLP-1 RAs and the risk of self-harm, suicidal ideation, and suicide. We will assemble a cohort of patients aged 18 and older who were newly prescribed a GLP-1 RAs or a dipeptidyl peptidase-4 (DPP-4) inhibitor between January 2007 and March 2021. We will use Cox proportional hazards models with propensity score fine stratification weighting to estimate hazard ratios and 95% confidence intervals for the incidence of a composite of suicide, suicidal ideation, and self-harm among GLP-1 RA users compared to DPP-4 inhibitor users. The outcomes of interest will be identified using data from the CPRD GOLD and Aurum, Hospital Episode Statistics, and Office for National Statistics databases. We will conduct analyses to assess the outcomes separately and to examine whether there is a duration-response relationship, and whether the relationship varies by drug, age, sex, history of depression, history of self-harm, body mass index, or socioeconomic status. The findings of this study could have relevant implications for prescribing practices for patients with type 2 diabetes.
The primary outcome will be a composite of the first occurrence of completed suicide, suicidal ideation, or self-harm resulting in hospitalization during the follow-up period. The secondary outcomes will be suicide, suicidal ideation, or self-harm assessed as standalone endpoints. Suicide and self-harm will be defined by ICD-10 codes; suicidal ideation will be defined by Read and SNOMED-CT codes.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Laurent Azoulay - Corresponding Applicant - McGill University
Hui Yin - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Samantha Shapiro - Collaborator - McGill University
Soham Rej - Collaborator - McGill University
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation