In this episode of Topical Conversations, Michael Cameron, MD, and James Allred, MD, explore the intersection of GIP and GLP-1 receptor agonists, such as tirzepatide and semaglutide, and inflammatory skin diseases like psoriasis, hidradenitis suppurativa (HS), and atopic dermatitis (AD). They discuss how these medications, originally developed for diabetes and weight management, are emerging as potential tools in dermatology, impacting the way clinicians can approach inflammatory conditions. 

GLP-1 receptor agonists: a game-changer for inflammation 

Dr Allred highlights how GLP-1 receptor agonists have shown significant anti-inflammatory effects, even before substantial weight loss occurs. Historically, weight reduction has been associated with improvements in inflammatory skin diseases but achieving it through diet and exercise alone is often challenging for many patients. GLP-1 receptor agonists provide a new avenue, reducing systemic inflammation and complementing existing therapies for psoriasis and other conditions. 

Dr Cameron adds that anecdotal evidence shows improvements in psoriasis, HS, and AD when these medications are used, often alongside biologics. He emphasizes that GLP-1 receptor agonists are becoming more accessible and commonly prescribed, making it crucial for dermatologists to understand their potential benefits. 

The role of visceral fat in inflammation 

Dr Allred explains the pathophysiology of visceral fat and its role in systemic inflammation. Unlike subcutaneous fat, visceral fat is hormonally active, releasing cytokines like IL-6 and TNF-alpha that exacerbate inflammatory diseases. He notes that GLP-1 receptor agonists reduce the inflammatory burden by targeting these fat cells, which are highly metabolically active and prone to cellular damage. 

Dr Cameron points out that some patients on GLP-1 receptor agonists experience marked improvements in their psoriasis even without concomitant biologics, suggesting the reduction in proinflammatory mediators from fat cells plays a significant role in disease improvement. 

Practical considerations for dermatologists 

1. Understanding the therapy: Dermatologists should familiarize themselves with the prescribing process for GLP-1 receptor agonists, including contraindications such as a history of medullary thyroid cancer or diabetes-related gastroparesis. These medications are relatively easy to initiate, requiring no specific lab monitoring. 
2. Holistic patient care: Dr Allred underscores the importance of screening patients with psoriasis for comorbidities such as obesity, lipid abnormalities, and metabolic syndrome. Addressing these factors can improve overall outcomes and complement traditional therapies. 
3. Expanding the scope of care: GLP-1 receptor agonists have often been considered the domain of endocrinologists and primary care providers, but Dr Allred advocates for dermatologists to take ownership of treating inflammation as part of managing inflammatory skin diseases. 

Future directions in research 

Dr Cameron concludes by previewing ongoing research comparing outcomes for patients on ixekizumab alone versus ixekizumab combined with GLP-1 receptor agonists. Early evidence suggests that this combination may amplify disease improvement in conditions like psoriasis and psoriatic arthritis. 

Dr Allred believes GLP-1 receptor agonists represent the next major evolution in psoriasis treatment, likening their impact to the revolutionary introduction of biologics. He encourages dermatologists to embrace this innovation to maximize the care they provide for their patients. 

Takeaways for Dermatologists 

• GIP and GLP-1 receptor agonists like tirzepatide and semaglutide offer promising anti-inflammatory benefits, particularly for overweight patients with psoriasis, HS, and AD 
• Understanding the role of visceral fat in systemic inflammation can help dermatologists appreciate the broader impact of weight management on skin health 
• Dermatologists should consider integrating GLP-1 receptor agonists into treatment plans where appropriate 
• Ongoing research will further elucidate the role of GLP-1 receptor agonists in dermatology, potentially paving the way for new treatment paradigms.