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.
There were 14,665 pairs of patients in the cohort for GLP-1RAs versus SGLT2is and 13,711 pairs in the cohort for GLP-1RAs versus DPP4is. Over the follow up period, 961 GLP-1RA users and 902 SGLT2i users were diagnosed with depression, indicating very little difference in risk for depression between GLP-1RAs and SGLT2is.
In the cohort comparing GLP-1RA and DPP4is treatment, 963 and 1075 depression events occurred, respectively, suggesting an antidepressant effect of GLP-1RAs. More research is needed to confirm these findings; however, the findings could have important implications on the management of diabetes and depression in older adults.
Reference:
Huilin Tang, Ying Lu, William T. Donahoo, et al. Glucagon-Like Peptide-1 Receptor Agonists and Risk for Depression in Older Adults With Type 2 Diabetes: A Target Trial Emulation Study. Ann Intern Med. [Epub 25 February 2025]. doi:10.7326/ANNALS-24-01347