Integrating GLP-1 Receptor Agonists in Psoriatic Disease: A Dual-Target Approach to Inflammation and Obesity
At the Fall Clinical 2025 session, “Keep the Conversation Going: Optimizing Psoriatic Disease Outcomes With GLP-1 Receptor Agonists,” presenters Erin E. Boh, MD, PhD; Karan Lal, DO; and Marc Serota, MD, delivered a compelling update on how glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists can be integrated into the management of psoriatic disease, particularly in patients with obesity and systemic comorbidities. The discussion centered on the dual role of these agents in reducing systemic inflammation and promoting weight loss—2 factors strongly linked to psoriasis pathophysiology and therapeutic response.
The session began with a review of psoriasis immunopathogenesis, tracing the activation of naïve T cells and their downstream differentiation based on cytokine exposure. In the presence of IL-23, T cells differentiate into Th17 cells, producing IL-17 and IL-22, which drive the epidermal inflammation seen in psoriatic plaques. These pathways overlap significantly with inflammatory pathways seen in obesity, diabetes, and metabolic syndrome.
Dr Boh emphasized the need to view psoriasis as a multiorgan disease, noting that patients frequently present with multiple overlapping comorbidities, including psoriatic arthritis, obesity, fatty liver disease, diabetes, and hypertension. “It’s those comorbidities that contribute to the recalcitrant nature of treatment,” she said.
Dr Boh presented a case of a woman with longstanding psoriasis who had cycled through multiple biologics with temporary improvement. She responded well to bimekizumab in terms of skin clearance but continued to experience joint flares and rising weight, now with a body mass index over 44. “She has tried every diet,” Dr Boh said. “But she still has a problem getting the weight off and keeping it off.”
Despite well-controlled hypertension and diabetes, the patient’s obesity remained unaddressed—a common scenario that impedes long-term psoriasis control.
Dr Serota, a board-certified dermatologist and obesity medicine specialist, described how he reframes obesity in the clinical conversation. “Optimizing your weight” is the phrase he uses to open a nonjudgmental discussion, especially in patients with comorbid psoriasis, hidradenitis suppurativa, or other inflammatory conditions.
Dr Lal echoed the importance of language and relatability. “I used to be 300 lb,” he shared. “When I tell my patients that, I can be blunt. I explain that the drugs we use aren’t weight-based, so a patient who weighs 400 lb may not respond the same as someone who weighs 200 lb.”
Both emphasized that while the inflammatory component of psoriasis is treated immunologically, one of the root causes—obesity—is often left unaddressed, perpetuating inflammation and hindering treatment response.
Dr Serota made the case for dermatologists to become more involved in weight-focused management. “Forty percent of the US qualifies as obese or overweight with a weight-related comorbidity,” he said. “That means nearly half the country is eligible for a GLP-1 receptor agonist.”
He added, “Even if you’re not comfortable prescribing them, you should know who to refer to.”
GLP-1s, and newer dual agonists like tirzepatide, which targets GLP-1 and GIP, have shown marked effects on weight loss and systemic inflammation, making them uniquely positioned to benefit dermatologic patients with inflammatory disease.
Dr Serota walked through the immunologic rationale for integrating obesity medicine into psoriatic disease management. Adipocyte hypertrophy, he explained, leads to hypoxia, which triggers adipocyte necrosis and tumor necrosis factor-alpha (TNF-α) production—a key cytokine in both obesity and psoriasis.
“When you look at patients with obesity, their fat tissue shows elevated levels of cytokines we already treat in psoriasis: TNF-α, IL-6, IL-1β,” he said. “Obesity is an inflammatory disease.”
He added that many psoriasis therapies show reduced efficacy in patients with obesity due to the challenge of drug distribution across hypertrophied adipose tissue.
Dr Serota expanded the conversation to include metabolic signaling. Leptin, which promotes satiety, is elevated in patients with obesity, yet these individuals remain hungry—a sign of leptin resistance. “It’s like insulin resistance in type 2 diabetes,” he said. “You have plenty of the hormone, but the receptors aren’t working.”
This dysregulation adds another layer to the metabolic-inflammation link in psoriatic disease and supports a more comprehensive treatment approach that includes metabolic correction alongside immune modulation.
The panel discussed how GLP-1s can be used alongside IL-17 or IL-23 inhibitors to address both immune activation and systemic inflammation. This approach is particularly helpful in patients who are partially responsive to biologics or plateau over time.
Dr Lal noted that many patients are now initiating these conversations themselves. “Patients come in asking, ‘Would this be a good option for me?’” he said. “That’s where we can change the conversation.”
Dr Serota added that GLP-1s are not just adjuncts but may enhance the overall effect of psoriasis therapies by reducing baseline inflammation and improving drug distribution and target engagement.
The panel concluded with a shared goal: normalizing the integration of GLP-1 therapy into psoriatic disease management. “This is not just about weight,” Dr Serota said. “This is about treating the whole patient.”
As GLP-1 receptor agonists become more widely available, dermatologists are well-positioned to adopt a dual-target approach, treating both inflammation and the metabolic dysfunction that fuels it. With thoughtful counseling and collaboration, these therapies can optimize long-term outcomes for patients living with psoriatic disease.
Reference
Boh E, Lal K, Serota M. Keep the conversation going: optimizing psoriatic disease outcomes with GLP-1 receptor agonists. Presented at: 2025 Fall Clinical Dermatology Conference. October 23–26, 2025; Virtual.
