GLP-1RAs may offer modest antidepressant effects compared to DPP4is but not SGLT-2is: Study

A target trial emulation study compared risk for depression among older adults with type 2 diabetes initiating treatment with glucagon-like peptide-1 agonists (GLP-1RAs) versus sodium–glucose cotransporter-2 inhibitors (SGLT2is) or dipeptidyl peptidase-4 inhibitors (DPP4is). The data showed that risk for depression was low overall, with no difference in incidence when comparing GLP-1RAs to SGLT2is and a modestly reduced risk with GLP-1RAs compared to DPP4is. The findings are published in Annals of Internal Medicine.

Some research has suggested the potential of GLP-1RAs to alleviate depression symptoms due to its ability to cross the blood-brain barrier, however, population-based studies have yielded inconsistent results.

Researchers from the University of Florida used U.S. national Medicare claims data between January 2013 and December 2020 to emulate a target trial assessing the risk of depression among older adults with diabetes initiating treatment with GLP-1RAs, SGLT2is or DPP4is. Participants were randomly assigned treatment to one of the three medications and were followed until the onset of depression, death, loss to follow-up, up to 2 years of follow-up, or the end of the study, whichever came first.