The finding:
This population-based retrospective cohort study utilized TriNetX Global Collaborative Network data encompassing electronic medical records (EMRs) from 113 health care organizations with around 8 million individuals diagnosed with type 2 diabetes (T2D), with over 83% residing in the United States. The study showed that the use of glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) (e.g.: liraglutide, semaglutide) is associated with lower suicide risk in people with T2D. The analysis comprised of four cohorts, differentiated based on the use of GLP‐1RA compared to dipeptidyl peptidase‐4 inhibitors (DPP‐4i) (e.g.: sitagliptin, saxagliptin) and the assessed suicide risk level. Those treated with GLP‐1RA exhibited a consistently lower risk of suicide attempts compared to those treated with a DPP‐4i. The high‐risk group of individuals with a history of depression or suicide attempts showed the same outcome and the risk ratios and ORs were significantly lower in the GLP‐1RA treated cohorts across all analyses.

Strength and weaknesses:
The study’s strengths lie in its large sample size, detailed stratification of people into specific cohorts based on their medical history allowed for a nuanced analysis of the treatment’s impact across different subgroups. There are several limitations including its retrospective nature inherently restricting the ability to establish causality, residual confounding factors may not have been accounted for or measured, reliance on EMRs and diagnostic codes may lead to underreporting of outcomes like suicide attempts, access to GLP-1RA in the US being a high-cost barrier potentially causing a selection bias. The study did not consider other factors that might be related to suicide, such as blood glucose control levels and episodes of hypoglycaemia, family history of suicide, and socioeconomic status.

Relevance:
The advent of GLP‐1RA has marked a significant advancement in the treatment of T2D, offering not just glycemic control but also benefits in weight loss and cardiovascular risk reduction. However, the safety profile of these agents has come under scrutiny. Concerns have been heightened by reports of rare yet severe psychiatric adverse events, including suicide and self‐injury. The FDA is currently assessing the necessity of regulatory measures following the receipt of reports in its FDA FAERS regarding suicidal ideation among individuals using GLP‐1RA. This study argues strongly against there being a potential for GLP‐1RA to cause an increase in suicide risk. While these findings require further investigation to fully understand the underlying mechanisms and broader clinical implications, this study is relevant to CL psychiatrists due to the widespread use of GLP-1RA medications in a general patient population encountered during routine CL psychiatry practice.