A new study confirms that GLP-1 drugs are safe for the mental health of diabetes

A large study analyzing data from over 60 million patients find no evidence that GLP-1 receptor agonists increase the risk of suicide Type 2 diabetes patientschallenges previous safety concerns.

study: Glucagon-like peptide-1 receptor agonists and risk of suicide in type 2 diabetes patients: an aggressive comparator, a new user cohort study. Image credit: azimmytws/shutterstock.com

recently BMJ Research determines the use of Glucagon– Peptide-1 (GLP-1) receptor agonists by type 2 diabetes (T2D) patients increase the risk of self-harm, suicidal ideation, and suicide compared to patients prescribed dipeptidylpeptidase-4 (DPP-4) or sodium-glucose coranose porter-2 (SGLT-2).

GLP-1 and the risk of suicide

The GLP-1 receptor agonist drug class is widely defined to manage T2D. These drugs are extremely effective in achieving glycemic control, while also promoting beneficial cardiac effects and reducing the risk of all-cause death.

After the Icelandic Drug Agency announced its initial safety concerns in July 2023, regulatory agencies around the world have launched a study to assess the potential risk of suicide among GLP-1 receptor agonist users. However, the lack of available evidence has limited researchers as it draws conclusive conclusions about this potential association.

This potential association may involve several mechanisms, some of which include sudden weight loss and hyperactivity of the hypothalamus-pituitary adrenal axis. Nevertheless, the exact way that the use of GLP-1 receptor agonists increases the risk of suicidal ideation and self-harm is still unknown.

About the research

The current observational study estimates the average therapeutic effect of serial GLP-1 receptor use on suicidal ideation, self-harm, and suicide in patients with T2D. Data from over 60 million patients treated with over 2,000 common practices were obtained from the UK clinical practice study Datalink (CPRD) Gold and Aurum.

Patients were divided into two cohorts. The first cohort constituted individuals who first started and continued GLP-1 receptor agonists or DPP-4 inhibitors between January 1, 2007 and December 31, 2020. The second group included individuals who had first continued either GLP-1 receptor agonists or SGLT-2 inhibitors on January 1, 2013 and December 31, 2020.

The main outcome was suicidal, which was defined as the combination of self-harm, suicidal ideation, or hospitalization for the completion of the suicide. Secondary results include that each of these events is being considered separately.

Survey results

This study cohort consisted of 36,082 and 234,028 GLP-1 receptor agonists and DPP-4 inhibitor users, respectively, with medians of 1.3 and 1.7 years. In comparison, 32,336 GLP-1 receptor agonists and 96,212 SGLT-2 inhibitor users were followed to medians of 1.2 and 1.2 years, respectively.

GLP-1 receptor agonist users had higher levels of hemoglobin_1c Longer periods of T2D. These individuals were also more likely to have a history of anxiety, depression, schizophrenia, self-harm, and insomnia.

The weighted incidence of suicide was 3.9 and 3.7 per 1,000 person-years for GLP-1 receptor agonists and DPP-4 inhibitor users. No significant differences in secondary outcomes were observed after weighting, and all results were consistent across multiple sensitivity analyses.

Before covariate weighting, GLP-1 receptor agonist users were obese, diagnosed with T2D for a longer period of time, with females being more elevated compared to SGLT-2 inhibitors prescribed. Patients using GLP-1 receptor agonists were also more likely to have a history of microvascular complications and depression.

The weighted incidence of suicide was 4.3 and 4.6 for every 1,000 person-years of individuals prescribed GLP-1 receptor agonists and SGLT-2 inhibitors, respectively. There were no significant differences in the secondary results after weighting between these two groups, and all results are consistent across multiple sensitivity analyses.

Conclusion

The findings show that the use of GLP-1 receptor agonists is not associated with increased risk of self-harm, suicidal ideation, and suicide compared to DPP-4 and SGLT-2 inhibitors in T2D patients.

The databases used in the current study allowed researchers to consider a wide range of confounding factors that are often absent in other management databases. Another important strength is the study design that minimizes bias associated with inclusion of common users without excluding patients with a history of self-harm or suicidal ideation. This is especially important. This is because individuals with a history of self-harm or suicidal ideation may be the most vulnerable to adverse psychiatric events associated with the use of GLP-1 receptor agonists.

A significant limitation of the current study is the potential presence of residual confounding. The database prescriptions only included those written by the GP, which allows for misclassification of exposure. Furthermore, the results of some secondary analyses need to be interpreted carefully due to broad confidence intervals due to the scarcity of the results.