GLP ‐ 1RAs and cardiovascular risk reduction in psoriasis: A retrospective cohort study

Psoriasis is a chronic inflammatory skin condition associated with an excess risk of cardiovascular events.1 Recent studies have highlighted the potential cardioprotective benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs), a class of medications primarily used to manage type 2 diabetes and obesity.2-4 However, it is unclear if these cardioprotective benefits extend to psoriasis patients. Our study aims to compare the incidence of major adverse cardiovascular events (MACEs) among those who use GLP-1RAs versus those who do not. We conducted a retrospective cohort study utilizing data from April 2005 to January 2025 in TriNetX, a research network providing electronic health record data from 69 healthcare organizations across the United States. Using ICD10-CM codes, we identified psoriasis patients aged ≥12 years who initiated GLP-1RA therapy. To identify psoriasis patients with no GLP-1RA use, we performed 1:1 propensity score matching by demographics, social factors, and common risk factors for MACE. Similar to methods from Ormaza Vera et al., the likelihood of MACE was evaluated using odds ratios (OR) with 95% confidence intervals at 5, 10 and 20 years following the index date, defined as the patient's first use of GLP-1RA after psoriasis diagnosis or, for non-users, date of psoriasis diagnosis.5 Patients with prior history of MACE were excluded from the analysis. We identified 646,438 patients with psoriasis. Among them, 41,873 (6.48%) used GLP-1RAs. These patients were propensity score matched to 41,873 psoriasis patients with no GLP-1RA use. GLP-1RA users with psoriasis, compared to non-users, were more likely to be older, female, tobacco users and to have metabolic disorders, obesity, diabetes mellitus, hypertensive disease, other forms of heart disease, diseases of arteries, arterioles and capillaries and disorders of lipoprotein metabolism and other lipidemias (std diff. ≥0.2). Within a 5-year observation window, GLP-1RA users with psoriasis had significantly lower odds of cerebrovascular disease (CVD) (OR 0.78 [0.71, 0.86]), heart failure (HF) (OR 0.84 [0.79, 0.89]), atherosclerosis (OR 0.81 [0.76, 0.87]) and percutaneous coronary intervention (PCI) (OR 0.59 [0.43, 0.81]) versus non-users (p < 0.05) (Figure 1). Significantly lower odds of these MACEs were also seen in GLP-1RA users at 10- and 20-year timepoints (Table 1). Although there were no significantly lower odds of ischaemic heart disease (IHD) within a 5-year observation window, there were significantly lower odds within the 10-year (OR 0.94 [0.89, 0.98]) and 20-year (OR 0.90 [0.86, 0.95]) observation windows. Our study highlights the potential cardioprotective benefits of GLP-1RAs in patients with psoriasis. Over 5-, 10- and 20-year observation periods, GLP-1RA users had significantly lower odds of CVD, HF, atherosclerosis and PCI versus non-users. Psoriasis patients using GLP-1RA also had significantly lower odds of IHD at 10- and 20-year timepoints. Limitations of our study include that TriNetX does not report length of GLP-1RA use or quantify psoriasis severity. Unmeasured confounding related to concomitant therapies should be considered when interpreting the results. Additionally, use of electronic health record (EHR) data may have introduced misclassification of diagnoses and incomplete capture of clinical events. Our results add to a growing body of evidence linking metabolic-targeted therapies to improved cardiovascular outcomes in chronic inflammatory diseases. Psoriasis-specific mechanisms of GLP-1RAs, including modulation of key immune cells and IL-23/Th17 axis suppression, highlight important clinical implications for psoriasis.6 Our findings in psoriasis align with those from our prior real-world cohort study in HS, in which GLP-1RA use was likewise associated with lower incidence of MACE.7 Future prospective studies and randomized clinical trials are needed to confirm these associations and to clarify the extent to which the observed benefits of GLP-1RAs in psoriasis reflect psoriasis-specific mechanisms versus broader cardiometabolic or anti-inflammatory effects. There were no funding sources for this study. AWA has served as a research investigator, scientific advisor and/or speaker to AbbVie, Amgen, Almirall, Arcutis, ASLAN, Beiersdorf, BI, BMS, EPI, Incyte, Leo, UCB, Janssen, Lilly, Novartis, Ortho, Sun, Dermavant, Dermira, Sanofi, Takeda, Regeneron and Pfizer. EJM, AMR, CYJ, PC, AK, YN, NJ, MY and MTO have no conflicts of interest to disclose. This study was considered exempt from review by the University of California, Los Angeles Institutional Review Board because all the data obtained by investigators were fully deidentified. The study was performed in full accordance with the Helsinki Declaration of 1975, as revised in 1983. The study used de-identified and aggregate data from electronic medical records that did not require written informed consent. The data that support the findings of this study are available from TrinetX. Restrictions apply to the availability of these data, which were used under licence for this study.