GLP-1RA and reduced mortality, cardiovascular and psychiatric risks in psoriasis: a large-scale cohort study

Psoriasis is associated with a significant comorbidity burden, especially cardiovascular and metabolic complications. Glucagon-like peptide-1 receptor agonists (GLP-1RA), such as semaglutide, used to treat obesity and diabetes, could potentially reduce comorbidity in patients with psoriasis. To investigate all-cause mortality, cardiovascular, inflammatory, psychiatric outcomes, and adverse events in psoriasis patients treated with GLP-1RA. This retrospective population-based cohort study utilized real-world data from the US TriNetX database. Patients with psoriasis who were treated for diabetes or obesity with GLP-1RA during the full follow-up period of 2 years were compared with those treated with other systemic anti-diabetic or obesity drugs. After 1:1 propensity-score matching for relevant risk factors, 3,048 participants were included in each cohort. The 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 results were further validated through two sensitivity analyses involving (i) later follow-up periods, or (ii) exclusion of patients with pustular psoriasis. In the matched cohorts of 3,048 patients with psoriasis treated with GLP-1RA (60.37% females, mean age 56.94 years, standard deviation SD 12.02 years) versus other antidiabetic and obesity drugs (61.91% females, mean age 56.42 years, SD 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<0.0001) and reduced risk for major adverse cardiac events (MACE, HR 0.561, 95% CI 0.442-0.714, p<0.0001). Additionally, lower risks for alcohol (HR 0.346, CI 0.174-0.685, p=0.009) and substance abuse (HR 0.510, CI 0.350-0.743, p=0.002) were observed. Typical adverse drug events were not more frequent in the GLP-1RA cohort. The risk reductions were more pronounced in the cohorts with psoriasis compared to persons with obesity or diabetes without psoriasis. Findings were consistent across all sensitivity analyses. 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.