GLP-1RAs lower depression risk in older adults with T2D

The incidence of depression among older adults with type 2 diabetes is low, and the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) helps reduce the risk of depression relative to dipeptidyl peptidase-4 inhibitors (DPP4is), but not sodium–glucose cotransporter-2 inhibitors (SGLT2is).

In this target trial emulation study, 14,665 matched pairs of older adults with T2D were included in the cohort for GLP-1RAs versus SGLT2is. The rate difference of depression between GLP-1RA users and SGLT2i users was 3.48 per 1,000 person-years (95 percent confidence interval [CI], –0.81 to 7.78; hazard ratio [HR], 1.07, 95 percent CI, 0.98–1.18).

In the cohort for GLP-1RAs versus DPP4is involving 13,711 matched pairs, the rate difference was –6.578 per 1,000 person-years (95 percent CI, –10.49 to –1.07; HR, 0.90, 95 percent CI, 0.82–0.98).

This study used US National Medicare administrative data from January 2014 to December 2020 to compare the risk for depression in older adults with T2D who initiated treatment with GLP-1RAs versus SGLT2is or DPP4is.

Adults aged 66 years or older with T2D treated with a GLP-1RA were matched 1:1 on propensity score with those treated with either an SGLT2i or DPP4i. Incident depression served as the primary endpoint. The investigators estimated the HRs with 95 percent CI within matched groups using Cox proportional hazards regression models.

The study was limited by unmeasured confounders (eg, haemoglobin A1c levels and BMI), outcome misclassification, and limited generalizability to all GLP-1RA users (eg, younger populations or those without T2D receiving the drug for obesity treatment).