Glucagon-like peptide-1 receptor agonists may reduce psoriasis severity in selected patients with metabolic comorbidities, although evidence remains limited and inconsistent, according to a narrative review from the National Psoriasis Foundation Medical Board published in JAMA Dermatology.
The review synthesized mechanistic and clinical data on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide/GLP-1 agonists in patients with psoriasis. Evidence from small randomized trials and prospective cohorts—typically enrolling 7 to 48 patients with follow-up of up to 6 months—suggested relative reductions in Psoriasis Area and Severity Index (PASI) scores of approximately 40% to 80%, particularly among patients with obesity or type 2 diabetes.
In an open-label randomized trial of 31 patients with obesity, type 2 diabetes, and psoriasis receiving metformin, semaglutide was associated with a 52% reduction in PASI scores over 12 weeks, along with improvements in lipid levels, glycemic control, and inflammatory markers. In another open-label randomized trial (n = 24) of patients with type 2 diabetes, no obesity, and psoriasis receiving background therapy, liraglutide was associated with an 83% reduction in PASI scores over 12 weeks.
However, findings were not consistent across study designs. The only placebo-controlled randomized trial included in the review enrolled 20 patients with obesity and psoriasis without diabetes and found that liraglutide produced weight loss but no statistically significant improvement in PASI scores compared with placebo.
Prospective cohort studies reported similar trends. A 6-month study of patients with obesity and psoriasis found a 48% reduction in PASI scores with semaglutide, accompanied by improvements in insulin resistance and fat distribution. Smaller liraglutide studies reported PASI reductions ranging from 23% to 85%, although the largest reductions were observed in very small cohorts.
The review also included large observational cohort data evaluating cardiometabolic outcomes in patients with psoriasis. In these studies, GLP-1 RA use was associated with lower risks of all-cause mortality and major adverse cardiovascular events compared with other therapies. One cohort specifically compared GLP-1 RAs with dipeptidyl peptidase-4 inhibitors in patients with immune-mediated inflammatory diseases and type 2 diabetes, a distinction that may be clinically relevant given potential effects of comparator therapies on psoriasis risk.
Mechanistic and translational findings suggest that psoriasis improvement may reflect both metabolic and immune effects, including reductions in C-reactive protein and interleukin-6 and changes in interleukin-17, interleukin-23, and dermal immune cell populations; in some studies, PASI improvement correlated more strongly with reductions in superficial adiposity than with overall body mass index.
From a clinical standpoint, the researchers noted that GLP-1 RAs can be coadministered with methotrexate, cyclosporine, and biologic therapies without clinically meaningful pharmacokinetic interactions. Adverse effects were primarily gastrointestinal, with rare risks including pancreatitis and gallbladder disease. Dermatologic adverse events included injection-site reactions, rare immune-mediated skin conditions, and a reported increased risk of hair loss with tirzepatide—likely related to telogen effluvium from rapid weight loss—although evidence for this association remains limited and inconsistent.
The authors emphasized that current evidence is limited by small sample sizes, short follow-up durations, and heterogeneity in study design, with most data derived from patients with obesity or type 2 diabetes. GLP-1 RAs are not approved for the treatment of psoriasis, and their use in this setting remains off-label, with prescribing typically driven by cardiometabolic indications.
“GLP-1 RAs, including dual GIP/GLP-1 agents, represent a biologically plausible and clinically intriguing adjunct in selected patients, although their definitive role in psoriasis management remains to be established,” the authors wrote.
Several researchers reported consulting, advisory, or research relationships with pharmaceutical companies, including manufacturers of GLP-1–based and dermatologic therapies.
Source: JAMA Dermatology
