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Cosmos Study

Most GLP-1 Medications Correlated with a Lower Likelihood of Anxiety and Depression Diagnoses

February 6, 2024
Dual-Team Study
Team A:Anna Miller, RNBrendan Joyce
Team B:Kersten Bartelt, RNJoe Deckert, PhD

Key Findings

  • Diabetic patients prescribed tirzepatide, semaglutide, dulaglutide, and exenatide are less likely to be diagnosed with depression after starting the medication compared to those not on a glucagon-like peptide-1 receptor agonist (GLP-1) medication.  
  • The likelihood of anxiety in diabetic patients is lower for those on all five GLP-1 medications studied. 
  • Among non-diabetic patients, semaglutide is correlated with a lower likelihood of depression and anxiety, while liraglutide showed no statistically significant difference compared to those on non-GLP-1 weight management medications. 

Glucagon-like peptide-1 receptor agonist (GLP-1) medications have been used for glucose control in diabetic patients for several years. Recently, the U.S. Food and Drug Administration (FDA) approved some GLP-1 medications, including semaglutide and liraglutide, for weight management in obese patients.1 Notably, one such medication, Wegovy, which has a main active ingredient of semaglutide, lists depression and suicidal ideation as potential side effects.2 Other GLP-1 medications, including another with semaglutide as a main active ingredient, do not list depression or suicidal ideation as potential side effects.3 An initial evaluation by the FDA suggests no direct link between GLP-1 medications and suicidal ideation.1 

To better understand the potential relationship between GLP-1 medications and mental health diagnoses after starting the medications, we studied 3,081,254 diabetic patients and 929,174 non-diabetic patients. We adjusted for patient age, sex, and history of depression or anxiety. For the diabetic population, we also adjusted for HbA1c level and use of other diabetic medications. For the non-diabetic population, we adjusted for BMI classification. For the diabetic population, we compared patients prescribed GLP-1 medications to patients with an HbA1c level documented. For the non-diabetic population, we compared patients prescribed GLP-1 medications to patients prescribed a non-GLP-1 weight management medication. 

We first investigated the correlation between GLP-1 medications and depression diagnosis after starting the medication. Among diabetic patients, those prescribed any of the GLP-1 medications studied, except for liraglutide, showed a decreased likelihood of depression compared to those not prescribed the GLP-1 medication. Tirzepatide showed the greatest reduction in likelihood of depression for diabetic patients (65%), as shown in Figure 1. Among non-diabetic patients, those prescribed semaglutide had a lower likelihood of depression compared to those not prescribed the GLP-1 medication. Liraglutide showed no statistically significant difference in depression diagnoses for non-diabetic patients. 

Figure 1
Depression Likelihood by GLP-1 Medication
Depression Likelihood by GLP-1 Medication
Figure 1. The likelihood of patients being diagnosed with depression after a GLP-1 prescription compared to those on a non-GLP-1 medication.

Next, we evaluated the relationship between GLP-1 medications and anxiety. Similar to depression, diabetic patients prescribed any of the GLP-1 medications had a lower likelihood of being diagnosed with anxiety after starting the medication compared to those not prescribed a GLP-1 medication. Tirzepatide showed the greatest reduction in likelihood, with a 60% reduction, as seen in Figure 2. Among non-diabetic patients, only those prescribed semaglutide had a lower likelihood of anxiety compared to those not prescribed the GLP-1 medication, while those prescribed liraglutide had no statistically significant difference. 

Figure 2
Anxiety Likelihood by GLP-1 Medication
Anxiety Likelihood by GLP-1 Medication
Figure 2. The likelihood of patients being diagnosed with anxiety after a GLP-1 prescription compared to those on a non-GLP-1 medication.

These data come from Cosmos, a collaboration of Epic health systems representing more than 233 million patient records from 1,325 hospitals and more than 28,900 clinics from all 50 states and Lebanon. This study was completed by two teams that worked independently, each composed of a clinician and research scientists. The two teams came to similar conclusions. Graphics by Brian Olson. 

References

  1. Update on FDA’s ongoing evaluation of reports of suicidal thoughts or actions in patients taking a certain type of medicines approved for type 2 diabetes and obesity. U.S. Food and Drug Administration. Published January 11, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/update-fdas-ongoing-evaluation-reports-suicidal-thoughts-or-actions-patients-taking-certain-type. Accessed January 16, 2024. 
  2. Common Side Effects of Wegovy®. Wegovy. https://www.wegovy.com/taking-wegovy/side-effects.html. Accessed January 16, 2024. 
  3. Possible Side Effects of Ozempic® (semaglutide) Injection. Ozempic. https://www.ozempic.com/how-to-take/side-effects.html. Accessed January 26, 2024.