Glucagon-like peptide-1 receptor agonists and reduced mortality, cardiovascular and psychiatric risks in patients with psoriasis: a large-scale cohort study

Background Psoriasis is associated with a significant comorbidity burden, especially cardiovascular and metabolic complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide, used to treat obesity and diabetes, could potentially reduce comorbidities in patients with psoriasis. Objectives To investigate all-cause mortality, cardiovascular, inflammatory and psychiatric outcomes, and adverse events in patients with psoriasis treated with GLP-1RAs. Methods This retrospective population-based cohort study used real-world data from the US TriNetX database. Patients with psoriasis who were treated for diabetes or obesity with a GLP-1RA during the follow-up period of 2 years were compared with those treated with other systemic antidiabetic or antiobesity drugs. After 1: 1 propensity score matching for relevant risk factors, 3048 participants were included in each cohort. Primary outcomes included the risk of cardiometabolic, psychiatric and autoimmune sequelae of psoriasis, as well as all-cause mortality and potential adverse drug events. The analysis was repeated using cohorts without psoriasis and the results were further validated through two sensitivity analyses involving (i) later follow-up periods or (ii) the exclusion of patients with pustular psoriasis. Results In the matched cohorts of 3048 patients with psoriasis treated with a GLP-1RA [60.4% women, mean (SD) age 56.94 (12.02) years] vs. other antidiabetic and antiobesity drugs [61.9% women, mean (SD) age 56.42 (14.16) years], GLP-1RA treatment was associated with significantly decreased all-cause mortality [hazard ratio (HR) 0.219, 95% confidence interval (CI) 0.123–0.391; P < 0.001] and reduced risk of major adverse cardiac events (HR 0.561, 95% CI 0.442–0.714; P < 0.001). Additionally, lower risks for alcohol (HR 0.346, 95% CI 0.174–0.685; P = 0.009) and substance abuse (HR 0.510, 95% CI 0.350–0.743; P = 0.002) were found. Typical adverse drug events were not more frequent in the GLP-1RA cohort. The risk reductions were more pronounced in the cohorts with psoriasis than in those with obesity or diabetes without psoriasis. The findings were consistent across all sensitivity analyses. Conclusions GLP-1RA treatment was safe and associated with reduced risks of cardiovascular and psychiatric comorbidities, as well as lower mortality in patients with psoriasis, with risk reductions markedly higher than in cohorts without psoriasis. Physicians should consider this drug class for patients with psoriasis and comorbid obesity or diabetes.