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Depression Risk Lower With GLP-1 Receptor Agonists Versus DPP-4 Inhibitors in Seniors

Medically reviewed by Carmen Pope, BPharm. Last updated on Feb 25, 2025.

By Elana Gotkine HealthDay Reporter

MONDAY, Feb. 24, 2025 -- For older adults with type 2 diabetes (T2D), use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is associated with a modestly lower risk for depression compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) use, according to a study published online Feb. 25 in the Annals of Internal Medicine.

Huilin Tang, Ph.D., from the University of Florida College of Pharmacy in Gainesville, and colleagues compared the risk for depression in older adults with T2D initiating treatment with GLP-1 RAs versus sodium-glucose cotransporter-2 inhibitors (SGLT-2is) or DPP-4is in a target trial emulation study using national Medicare administrative data from January 2014 to December 2020. Adults aged 66 years or older with T2D initiating treatment with a GLP-1 RA were propensity score-matched to those initiating treatment with an SGLT-2i (14,665 matched pairs) or a DPP-4i (13,711 matched pairs).

The researchers found that the rate difference of depression was 3.48 per 1,000 person-years between GLP-1 RA users and SGLT-2i users (hazard ratio, 1.07; 95 percent confidence interval, 0.98 to 1.18). The rate difference was −5.78 per 1,000 person-years for GLP-1 RA users versus DPP-4i users (hazard ratio, 0.90; 95 percent confidence interval, 0.82 to 0.98).

"These results, if confirmed in randomized controlled trials, could have important implications for the management of T2D, especially in older patients at risk for depression," the authors write.

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Disclaimer: Statistical data in medical articles provide general trends and do not pertain to individuals. Individual factors can vary greatly. Always seek personalized medical advice for individual healthcare decisions.

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Posted February 2025

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