Risk of depression and dementia among individuals treated with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists.

Abstract

Purpose of the review: To review whether sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists decrease the risk of depression, suicidal ideation and cognitive impairment in later life.

Recent findings: The results of studies using information derived from large registries and administrative health datasets suggest that GLP-1 receptor agonists (RAs) increase the risk of suicidality, although findings have been inconsistent. One nested-case control study reported that SGLT2i decreases the risk of depression among adults with diabetes, and findings from a small trial of the SGLT2i empagliflozin provided supportive evidence. Several observational studies reported that SGLT2i and GLP-1 RAs decrease dementia risk, with a target trial finding greater cognitive benefit associated with the use of GLP-1 RAs compared with other medicines commonly used to manage diabetes.

Summary: Recent results from large observational studies suggest that SGLT2i and GLP-1 RA may decrease the risk of cognitive impairment in later life. The effects of these medicines on mood have not been as well explored, but there are concerns about the potential increased risk of suicidality among GLP-1 RA users. Prescription bias could explain some of these associations, so that robust trial evidence is now needed to confirm or dismiss the reported findings.