Large Study Finds GLP-1 Drugs Do Not Increase Depression Risk Compared to SGLT2 Inhibitors | Research

The takeaway

A new-user active-comparator cohort study comparing GLP-1 receptor agonists with SGLT2 inhibitors found no increased risk of depression with GLP-1 drugs in overweight/obese type 2 diabetes patients.

No increased depression risk
GLP-1 RA vs SGLT2i in propensity-matched overweight/obese T2D cohort

What the researchers found

GLP-1 receptor agonist use was not associated with increased depression risk compared to SGLT2 inhibitor use in a propensity-matched cohort of overweight/obese T2D patients.

Why it matters

Depression concerns have been raised about GLP-1 drugs, with some regulatory agencies investigating. This large real-world study provides reassuring evidence for the millions of people taking these medications.

How the study worked

New-user, active-comparator cohort study with 1:1 propensity score matching using deidentified EHR data from January 2016 to July 2024.

What this study cannot tell us

Observational study cannot prove absence of risk; EHR data may underdiagnose depression; SGLT2i comparator group may not represent true baseline risk.

How to read the evidence

Well-designed active-comparator cohort study with propensity matching — strong observational evidence addressing a specific safety concern.

When this study was published

Published in 2026, providing timely evidence as regulatory agencies investigate GLP-1 drug psychiatric safety.

The bigger picture

As GLP-1 drugs are prescribed to tens of millions globally, establishing their psychiatric safety profile is critical. This study adds to growing evidence that these drugs do not increase depression risk.

Questions still open

Do specific GLP-1 drugs (semaglutide vs liraglutide) differ in depression risk?
Could GLP-1 drugs actually improve mood through weight loss and metabolic improvements?

Common questions

Do GLP-1 drugs like Ozempic cause depression?

This large study found no increased depression risk with GLP-1 drugs compared to another diabetes drug class (SGLT2 inhibitors), providing reassurance despite some earlier case reports of mood changes.

Why were there concerns about GLP-1 drugs and depression?

Some patients reported mood changes, and regulatory agencies opened investigations. However, controlled studies like this one have generally not found an increased risk, suggesting individual experiences may not reflect a drug-class effect.

Read the original research

Risk of depression with GLP-1 receptor agonists use in overweight or obese adults with type 2 diabetes: A new-user, active-comparator cohort study.

Diabetes, obesity & metabolism, 28(1), 197-209

View on PubMed ↗Publisher’s paper ↗

Citation

Chang, Yu; Hsieh, Ming-Hong; Ju, Po-Chung; Chang, Cheng-Chen. (2026). Risk of depression with GLP-1 receptor agonists use in overweight or obese adults with type 2 diabetes: A new-user, active-comparator cohort study.. Diabetes, obesity & metabolism, 28(1), 197-209. https://doi.org/10.1111/dom.70175