GLP-1 Drugs May Offer Antidepressant Effects

A study led by researchers in the University of Florida College of Pharmacy has found that GLP-1RAs, a class of glucose-lowering medication, may offer antidepressant effects.

In a National Institutes of Health-funded study published in the Annals of Internal Medicine on Feb. 25, UF researchers studied Medicare claims data of older adults with Type 2 diabetes to assess their risk of depression while undergoing treatment with either GLP-1RAs, SGLT2is or DPP4is.

The 28,000 study participants were randomly assigned treatment with one of the three medications, and their health was followed for up to two years until the onset of depression symptoms or death or until they could no longer be contacted.

The data showed a modestly reduced risk of depression with GLP-1RAs when compared with DPP4is and a negligible difference in depression risk between GLP-1RAs and SGLT2is.

Serena Jingchuan Guo, M.D., Ph.D., an assistant professor of pharmaceutical outcomes and policy in the UF College of Pharmacy and the study’s senior author, said this research carries significant implications for older patients with diabetes, a group that has a higher depression risk than the general population.

“Depression occurs two to three times more frequently in people with Type 2 diabetes than in those without diabetes, and it negatively affects their diabetes management,” Guo said. “Given the substantial disease burden and adverse health outcomes associated with this comorbidity, interventions aimed at reducing this risk for depression in the Type 2 diabetes population are crucial, particularly among older adults who are disproportionately affected by both conditions.”

Guo noted that previous research suggested that GLP-1RAs — a drug also used to treat obesity and kidney disease — may alleviate depression symptoms due to its ability to cross the blood-brain barrier. In response to the modest and mixed results gleaned from this study, Guo said her team of researchers plans to continue investigating the potential antidepressant effects of GLP-1RAs.

“The minimal difference in depression risk between GLP-1RAs and SGLT2is suggests that both classes of drugs may have similar effects on mood regulation. This finding highlights the need for further research to understand the mechanisms through which these medications influence mental health and to identify which patient populations might benefit the most from each treatment,” Guo said.

To fully understand the role of GLP-1RAs in managing diabetes and depression, further randomized controlled trials and long-term studies are needed, Guo added.

Reference: Tang H, Lu Y, Donahoo WT, et al. Glucagon-Like Peptide-1 Receptor Agonists and Risk for Depression in Older Adults With Type 2 Diabetes. Ann Intern Med. 2025. doi: 10.7326/ANNALS-24-01347

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