U.S. veterans have a high prevalence of post-traumatic stress disorder (PTSD), for which no effective psychotropic medications are indicated. Nearly 25% of veterans have diabetes, for which metformin is a first line treatment. Although metformin is associated with improved neurodegenerative outcomes, there is no evidence on the association between metformin and PTSD-related symptom relief. This study aimed to examine whether metformin was associated with a clinically meaningful reduction in PTSD symptoms (≥20 points reduction PTSD checklist for DSM-5 {PCL-5}) score)) among veterans with PTSD using data from Veterans Health Administration. The metformin cohort was defined as first metformin use after a recorded PTSD diagnosis with a PCL-5 score ≥33 (i.e., clinical cut-score). The control cohort (never used metformin) was selected by propensity score 1:1 matching on the likelihood of initiating metformin with the covariates of age, gender, race, durations of PTSD, diabetes, and depression, and baseline CCI, PCL-5, and PHQ-9 scores. Multivariable Cox proportional regression was used to assess the association between metformin exposure and improvement in the PCL-5 scores. A total of 7950 veterans (mean age: 51.9 ± 13.6 years, male: 85%, white: 61.4%, African American: 28.8%) with confirmed PTSD were comparable on the baseline demographics and medical conditions between metformin and control PSM-matched cohorts with a median follow-up 1.2 years in both cohorts. The baseline PCL-5 score was 56.2±11.6 and 56.5±11.7 in metformin and control cohort, respectively. The metformin-treated cohort was more likely to have a clinically meaningful reduction in PTSD symptoms (adjusted hazard ratio (aHR): 1.31, 95%CI: 1.16-1.48), compared the control cohort. Furthermore, patients on metformin ≥2 years were 22% more likely to reduce PTSD symptoms (aHR: 1.22, 95%CI: 1.04-1.43), compared with metformin exposure <2 years. Metformin exposure may be beneficial to PTSD symptoms among veterans.


S. Liu: None. A.M. Raines: None. Y. Yoshida: None. W. Tang: None. J.I. Constans: None. V. Fonseca: Consultant; Self; Abbott, Asahi Kasei Corporation, AstraZeneca, Bayer Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Stock/Shareholder; Self; Amgen, Bravo4health. L. Shi: None.

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