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

Written by Dr. Kamal Kant Kohli Published On 2025-02-25T22:45:32+05:30 | Updated On 25 Feb 2025 10:46 PM IST

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

Annals of Internal Medicineantidepressanttype 2 diabetesglucagon like peptide-1 agonistssodium glucose cotransporter-2 inhibitors

Source : Annals of Internal Medicine

Dr. Kamal Kant Kohli

Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Email: drkohli@medicaldialogues.in. Contact no. 011-43720751