Role of GLP-1 Drugs in Psoriasis and PsA Is Debated

Medscape

a day ago

BOGOTÁ, Colombia — Most dermatologists and rheumatologists agree that GLP-1 receptor agonists (GLP-1 RAs), such as liraglutide, semaglutide, and tirzepatide, powerful antidiabetes and weight-loss drugs, have the potential to help some patients with psoriasis and psoriatic arthritis (PsA).
Besides mitigating obesity, an established risk factor for psoriasis and PsA, GLP-1 drugs have shown promise in improving psoriasis symptoms and are associated with a lower risk for cardiovascular events, for which people with psoriasis and PsA are at increased risk. Some researchers predict that the drugs will prove to have immunomodulatory effects and become an important addition to current treatments for psoriasis and PsA, even in patients without obesity or diabetes.
At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2025 Annual Meeting and Trainee Symposium, investigators with the GRAPPA dove into hours' worth of discussions and debates about a class of drugs whose emergence Artie Kavanaugh, MD, professor of medicine at the University of California, San Diego, described as a possible 'watershed moment' for the field, akin to the advent of biologic therapies in the 1990s.
But with evidence still sparse in patients with psoriatic disease and ancillary concerns about access, cost, patient selection, and physician confidence in prescribing, there was little agreement as to how, whether, or when these drugs should be integrated into clinical practice.
A GLP-1 Pioneer
Endocrinologist Daniel J. Drucker, MD, professor in the Department of Medicine's Division of Endocrinology, University of Toronto, Ontario, Canada, who discovered some key biological actions of the hormone GLP-1 in the 1980s and '90s, kicked off the conference with a video presentation affirming GLP-1 RAs potential as immunoregulatory agents with anti-inflammatory activity beyond their well-documented effects on body weight.
In a 2023 trial of semaglutide in patients with obesity who did not have diabetes, Drucker noted prevention of cardiovascular events and death was seen as independent of weight loss. Similarly, Drucker said, a recent trial in people with metabolic liver disease saw improvements associated with semaglutide that were independent of weight loss.
With psoriasis and PsA, randomized controlled trial evidence has yet to support weight-loss independent improvements in symptoms. However, this may soon change: In two separate trials, Eli Lilly is studying a combination of tirzepatide and the interleukin-17A antagonist ixekizumab in patients with overweight or obesity and psoriasis or PsA. The trials will wrap up next summer.
Results from trials of GLP-1 inhibitors in nonobese populations, including cohorts of people with Alzheimer's disease, stand to shed further light on their anti-inflammatory effects outside the context of weight loss, Drucker said.
'These medicines are diversifying. We're going to see a wave of new molecules and new indications to treat inflammation,' he predicted, including that of skin, joints, and bone. Still, Drucker cautioned, the drugs 'are not magic bullets, and each condition will need to be assessed on its own.'
Real-World Experience From Latin America
In a subsequent talk, Enrique Soriano, MD, head of rheumatology at the Hospital Italiano de Buenos Aires, Buenos Aires, Argentina, presented a real-world perspective from Latin America, where GLP-1 drugs are approved in most countries for diabetes or obesity — but still not easy to access and far from becoming a routine part of any rheumatologist's or dermatologist's daily practice.
'We all know that obesity increases the risk of developing psoriatic arthritis in psoriasis patients,' Soriano said — and that weight loss can decrease that risk. 'We also know that treatment response is lower in PsA patients with obesity,' he said. 'But the question for us is whether this drug [class] can improve symptoms and inflammation in our patients and whether this improvement, if it happens, is related to the weight loss or is an independent effect.'
Soriano presented a retrospective review from his institution's service of 6800 patients with psoriasis (mostly mild) and 488 with PsA. In each group, just over 1% of patients were taking a GLP-1 RA for obesity, diabetes, or both. While acknowledging the limitations of his study's retrospective design, Soriano noted that 'there was no report of any improvement or change in the skin involvement, and there was also no record of any change in their joint symptoms after starting these drugs.'
Soriano also conducted a survey of rheumatologists across several countries in Latin America and found that under a third said that they had encountered a patient whom they thought could benefit from the addition of a GLP-1 drug, while fewer than 10% said that they would feel confident prescribing one. More than half said that if they did think a patient could benefit, they would refer that person to a specialist, such as an endocrinologist.
Dermatologist Describes Current Data as 'Weak'
Anthony Fernandez, MD, PhD, director of medical and inpatient dermatology at the Cleveland Clinic, Cleveland, praised GLP-1 RAs as 'fascinating medications' with 'a very attractive adverse event profile.'
Fernandez cited studies dating back over a decade in which use of these medications has been shown to improve psoriasis. 'And we have some data to suggest that the mechanism…is not entirely related to weight loss. In fact, there's data to support that these medications affect psoriasis-relevant immune pathways. So, in that way, they share similarities with many of the systemic medicines that we already prescribe to treat psoriasis.'
Still, Fernandez cautioned, 'The data right now is really weak,' limited to small studies and randomized trials enrolling mostly men. While a few patients in these studies saw dramatic improvements in psoriasis after starting these drugs, 'the reality is that most have, at best, a modest improvement,' he said, 'certainly nowhere near the improvement we are used to seeing' from targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) and biologic DMARDs (bDMARDs).
Moreover, he said, some patients enrolled in the studies were effectively treatment naive. 'That raises a critical question about whether or not a patient [on ts- or bDMARDs] would actually see any further improvement adding GLP-1 RAs,' he said.
Fernandez said he thought that dermatologists can safely prescribe and manage GLP-1 therapies. The bigger question is whether they should.
'My opinion is no,' he concluded. 'There will be rare patients who are obese and or have type 2 diabetes and either fail or have a contraindication to all the great systemic medicines we already have available to us. And in those patients, a trial of a GLP-1 RA would seem to be reasonable. But personally, I think we need much, much better data for recommendations concerning general use by dermatologists.'
During a question-and-answer period after Soriano's and Fernandez's presentations, other physicians shared their experiences and practical concerns about insurance approvals, referrals, and whether most dermatologists and rheumatologists were simply too busy to manage all the comorbidities of chronic immune-mediated disease for their patients. Some shared anecdotes about patients whose disease had improved after treatment with GLP-1 RAs, including in the absence of other systemic therapies.
Patients Intrigued — but Share Clinician's Caution
At the same session, Suzanne Grieb, PhD, a patient research participant (PRP) with GRAPPA and assistant professor at Johns Hopkins University, Baltimore , presented results from a survey of her fellow GRAPPA PRPs about their experiences and interests regarding GLP-1 drugs.
None of the 11 respondents reported having been prescribed the medications.
'The majority of us described our psoriatic disease as mostly manageable with our current treatment,' Grieb, who has PsA, told the conference.
However, that did not mean they weren't curious about GLP-1s. Grieb's survey revealed that while all participants were aware of the importance of exercise and healthy weight in disease management, many continued to struggle with both. Few reported having spoken with their providers about specific interventions. While three respondents expressed interest in taking GLP-1s, they were uncertain whether they would be able to access them.
Patients 'are interested in GLP-1s' impact on our psoriatic disease, but also on other elements of our health, thinking more holistically [about] the benefits that could be achieved through these medications,' Grieb said. But the respondents in her survey also reported concerns about adding medications and 'the potential for having to take this medication for the rest of our lives.'
In an interview after her presentation, Grieb elaborated on her personal perspective. 'I don't meet the requirement for obesity,' she said. 'But I'm overweight, and I could probably benefit from a GLP-1. Without clear weight-related indications, it's hard, perhaps to be able to justify prescribing it if it's not going to be available. So it's a hard conversation [for clinicians] to bring up with their patients.'