New Study Confirms GLP-1 Drugs Are Safe for Mental Health in Diabetes

New Study Confirms GLP-1 Drugs Are Safe for Mental Health in Diabetes

A large study analyzing data from over 60 million patients finds no evidence that GLP-1 receptor agonists increase the risk of suicidality in patients with type 2 diabetes, challenging previous safety concerns.

A current oneBMJThe study will determine whether the use of glucagon-like peptide-1 (GLP-1) receptor agonists in type 2 (T2D) patients reduces the risk of self-harm, suicidal ideation and suicide compared to patients with dipeptidyl peptidase-4 (DPP-4) or sodium glucose cotranporter-2 (SGLT-2) inhibitors (SGLT-2) inhibitors (SGLT-2) inhibitor increased.

GLP-1 and the risk of suicide version

The GLP-1 receptor agonist drug class is widely prescribed for the treatment of T2D. These drugs achieve glycemic control very effectively while promoting beneficial cardiorenal effects and reducing the risk of all-cause mortality.

After the Icelandic Medicines Agency published initial safety concerns in July 2023, regulators worldwide have launched investigations to assess the potential risk of suicide among users of GLP-1 receptor agonists. However, the lack of available evidence has limited researchers' ability to draw definitive conclusions about this potential link.

Multiple mechanisms may be involved in this potential association, some of which include sudden weight loss and hyperactivity of the hypothalamic-pituitary-adrenal axis. However, the exact manner in which the risk of suicidal ideation and self-harm may be increased by the use of GLP-1 receptor agonists remains unclear.

About the study

The current observational study estimates the average treatment effect of continuous GLP-1 receptor agonist use on suicidal ideation, self-harm, and suicide in T2D patients. Data from over 60 million patients treated in over 2,000 GP practices was obtained from the UK Clinical Practice Research Datalink (CPRD) Gold and Aurum.

The patients were divided into two cohorts. The first cohort included individuals who continued a GLP-1 receptor agonist or a DPP-4 inhibitor for the first time between January 1, 2007 and December 31, 2020. The second group included people who first met between January 1, 2013 and December 31, and December 31, and December 31, 2020, and December 31, 2020, and December 31, 2020, and 2020, and 2020, and 2020, and 2020, 2020.

The primary outcome was suicidality, which was defined as the composite of hospital admission for self-harm, suicidal ideation, or completed suicide. Secondary outcomes included each of these events separately.

Study results

The study cohort consisted of 36,082 and 234,028 GLP-1 receptor agonist and DPP-4 inhibitor users followed for a median of 1.3 and 1.7 years, respectively. In comparison, 32,336 GLP-1 receptor agonist and 96,212 SGLT-2 inhibitor users were followed for a median of 1.2 and 1.2 years, respectively.

GLP-1 receptor agonist users had higher hemoglobin A1C levels and longer T2D duration. These individuals were also more likely to have a history of anxiety, depression, schizophrenia, self-harm and insomnia.

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

Before covariate weighting, GLP-1 receptor agonist users were more likely to be obese, diagnosed with T2D for a longer duration, and diagnosed female compared to those prescribed SGLT-2 inhibitors. Patients with GLP-1 receptor agonists also had a higher frequency of microvascular complications and a history of depression.

The weighted incidence of suicidality was 4.3 and 4.6 per 1000 person-years in subjects prescribed GLP-1 receptor agonists and SGLT-2 inhibitors, respectively. No significant differences in secondary outcomes by weight were found between these two groups, with all results consistent across multiple sensitivity analyses.

Conclusions

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

The database used for the current study allowed researchers to account for a wide range of confounding factors that are often not present in other administrative databases. Another important strength is the study design, which minimized biases associated with the inclusion of prevalent users without excluding patients with self-harm or suicidal ideation. This is particularly important because individuals with self-harm or suicidal ideation may be most vulnerable to adverse psychiatric events associated with GLP-1 receptor agonist use.

A notable limitation of the current study is the potential presence of residual confounding. Exposure misclassification is also possible as the prescriptions in the database are only those written by general practitioners. In addition, the results of some secondary analyzes should be interpreted with caution, as wide-spread confidence intervals arise from the rarity of the results.

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