DEPRESSION SEVERITY CHANGE FOLLOWING INITIATION OF GLP-1 VERSUS NON-GLP-1 ANTI-OBESITY MEDICATIONS USING REAL WORLD DATA
Author(s)
Claire E. Campbell, PhD, Sarah Eng, MPH, Jeffrey Ratto, DrPH, Katherine Kendrick, MPH, Amy Austin, MHI, Ekaterina Khlystova, PhD, Sunny Guin, PhD, Vidya Venkataraman, MPH, PhD.
Truveta, Bellevue, WA, USA.
Truveta, Bellevue, WA, USA.
OBJECTIVES: This study evaluated differences in depression severity change among adults with obesity and depression initiating GLP-1 versus non-GLP-1 anti-obesity medications.
METHODS: This retrospective observational cohort study used de-identified electronic health record (EHR) data from Truveta, which includes data from more than 130 million patients across US health systems. Adults initiating a GLP-1 or non-GLP-1 anti-obesity medication (index date) between 2022 and 2024 were included. Eligible patients had an obesity diagnosis or a BMI≥30 kg/m² within 180 days before index, a depression diagnosis ≤1 year before index, a PHQ-9 score within 180 days before index, and ≥1 EHR record in the year pre-index. Patients were excluded if they had prior anti-obesity medication use, evidence of diabetes, or pregnancy during the 365 days before index or follow-up period, or medication use indicating a switch between treatment groups after index. The primary outcome was a PHQ-9 change score from baseline to follow-up. Multivariate linear regression was used to estimate the association between treatment group and PHQ-9 change, adjusting for demographic characteristics, comorbidities, psychiatric medications, healthcare utilization, baseline BMI, baseline PHQ-9 score, and other covariates.
RESULTS: Adjusted mean PHQ-9 scores increased slightly in both groups, by 0.33 points among GLP-1 initiators and 0.56 points among non-GLP-1 initiators. GLP-1 initiation was associated with a 0.22-point smaller increase in PHQ-9 score versus non-GLP-1 initiation (p=0.043), but this association was attenuated after excluding high-leverage observations (p=0.07). The observed difference was small and unlikely to be clinically meaningful.
CONCLUSIONS: GLP-1 initiation was associated with a small difference in PHQ-9 change compared with non-GLP-1 initiation over approximately 6 months, but the association was sensitive to exclusion of high-leverage observations and was unlikely to be clinically meaningful. Longer follow-up is needed to determine whether these modest differences persist or translate into clinically meaningful improvements in depressive symptoms.
METHODS: This retrospective observational cohort study used de-identified electronic health record (EHR) data from Truveta, which includes data from more than 130 million patients across US health systems. Adults initiating a GLP-1 or non-GLP-1 anti-obesity medication (index date) between 2022 and 2024 were included. Eligible patients had an obesity diagnosis or a BMI≥30 kg/m² within 180 days before index, a depression diagnosis ≤1 year before index, a PHQ-9 score within 180 days before index, and ≥1 EHR record in the year pre-index. Patients were excluded if they had prior anti-obesity medication use, evidence of diabetes, or pregnancy during the 365 days before index or follow-up period, or medication use indicating a switch between treatment groups after index. The primary outcome was a PHQ-9 change score from baseline to follow-up. Multivariate linear regression was used to estimate the association between treatment group and PHQ-9 change, adjusting for demographic characteristics, comorbidities, psychiatric medications, healthcare utilization, baseline BMI, baseline PHQ-9 score, and other covariates.
RESULTS: Adjusted mean PHQ-9 scores increased slightly in both groups, by 0.33 points among GLP-1 initiators and 0.56 points among non-GLP-1 initiators. GLP-1 initiation was associated with a 0.22-point smaller increase in PHQ-9 score versus non-GLP-1 initiation (p=0.043), but this association was attenuated after excluding high-leverage observations (p=0.07). The observed difference was small and unlikely to be clinically meaningful.
CONCLUSIONS: GLP-1 initiation was associated with a small difference in PHQ-9 change compared with non-GLP-1 initiation over approximately 6 months, but the association was sensitive to exclusion of high-leverage observations and was unlikely to be clinically meaningful. Longer follow-up is needed to determine whether these modest differences persist or translate into clinically meaningful improvements in depressive symptoms.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO56
Topic
Clinical Outcomes, Real World Data & Information Systems, Study Approaches
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Diabetes/Endocrine/Metabolic Disorders (including obesity), Mental Health (including addiction)