Emerging data about benefits of the newer weight-loss drugs for some chronic skin conditions suggests their potential use in dermatology, as well as a role for dermatologists in obesity management.
Glucagon like peptide 1 receptor agonist (GLP-1 RA) medications began as treatments for type 2 diabetes (T2D), then emerged as weight-loss drugs. The newer generation of these medications, semaglutide (Ozempic and Rybelsus for T2D, Wegovy for weight reduction) and the dual GLP-1/ glucose-dependent insulinotropic polypeptide agonist tirzepatide (Mounjaro for T2D, Zepbound for weight), are more potent for both conditions than first-generation predecessors, such as liraglutide (Victoza for T2D, Saxenda for weight loss) and exenatide (Byetta for T2D).
More recently, semaglutide was approved for reducing cardiovascular risk and to prevent kidney disease worsening in people with T2D and tirzepatide for treating obstructive sleep apnea. The agents have also shown benefits in studies of a wide range of other conditions, including those of the skin.
Thus far, psoriasis and psoriatic arthritis are the most-studied skin conditions with GLP-1 RA medications, but data also suggest the agents can improve symptoms of hidradenitis suppurativa (HS) and promote wound healing. Much of the effect appears to be secondary to the weight loss, but the GLP-1 RA drugs may also impart independent anti-inflammatory properties. Moreover, GLP-1 receptors (GLP-1Rs) have been identified in the skin, suggesting yet another independent mechanism.
"We know that weight loss, even with just a dietary modification, can reduce psoriasis severity and improve cardiovascular outcomes. However, GLP-1 Rs are actually found not just in fat and in the pancreas but also in skin cells, in hair follicles, and in immune cells. So by acting on those cells, there is a direct wound healing property and direct anti-inflammatory property," Dermatologist Naiem T. Issa, MD, PhD, who practices in Vienna, Virginia, told Medscape Medical News.
Issa, who holds academic appointments at the University of Miami, Miami, and The George Washington University, Washington, DC, co-authored a recently published review paper summarizing the effects of GLP-1 in dermatology. Included are the evidence for GLP-1 Rs in the skin, as well as the drugs' effects in wound healing, psoriasis, and HS. The authors also review the cutaneous side effects of GLP-1 RA medications.
"Dermatologists can think about prescribing these drugs beyond just a cosmetic outcome. They may be useful for patients with diabetes or obesity who have trouble with wound healing. That's really exciting," Issa said.
Eli Lilly and Company is currently conducting two Phase 3 trials, TOGETHER-PsO and TOGETHER-PsA, investigating the use of tirzepatide in combination with ixekizumab for adults with moderate or severe psoriasis or active psoriatic arthritis, respectively. Two Phase 4 studies will further investigate the effect of adding tirzepatide to standard treatment in clinical practice. Results are expected in 2026, a Lilly spokesperson told Medscape Medical News.
About "38% of people with psoriasis have obesity and up to 48% of people with psoriatic arthritis have obesity....Because of this, we are accelerating additional research to potentially support better health outcomes for people living with either of these immune system conditions as well as obesity or overweight," said the Lilly spokesperson, while declining to comment on specific regulatory submissions.
Joel M. Gelfand, MD, director of both the Psoriasis and Phototherapy Treatment Center and the Center for Clinical Sciences in Dermatology at Penn Medicine, Philadelphia, told Medscape Medical News that GLP-1 RAs could potentially have a major impact on the treatment of psoriasis in people who also have obesity.
"Obesity is a major driver of psoriasis. It is a risk factor for developing psoriasis, and for developing psoriatic arthritis within psoriasis. It makes people less responsive to treatment and more likely to lose response to treatment over time," he said. It is also "a major driver" of diseases like diabetes, as well as cardiovascular events and premature mortality, "so in theory, GLP-1s potentially address an enormous amount of unmet medical need in the space of psoriasis."
Gelfand noted that for some patients, "once their obesity is treated, their psoriasis may become mild enough that they might not need topicals or other psoriasis treatments at all. So it may switch the paradigm for those with psoriasis and obesity where you treat the obesity first, and then see what's left of the skin disease that needs to be treated."
However, Gelfand also cautioned that dermatologists might encounter a variety of barriers to prescribing GLP-1 RAs. "They have a lot of side effects. You need to know how to titrate the dose carefully. You have to counsel the patient carefully...Who's going to answer the phone that Friday night when the patient is having nausea, vomiting, or abdominal pain? So I think dermatologists need to think about this before prescribing these drugs. That said, at a minimum, we should be making our patients aware of GLP-1 RAs and encouraging them to speak to their primary care or other related type of provider who could prescribe them."
Gelfand added, "I think that we need to think of these patients holistically. People with psoriasis are very prone to cardiometabolic disease, including obesity, insulin resistance and diabetes, hypertension, dyslipidemia, atherosclerotic disease and cardiovascular events, and mortality. So we need to educate patients about these relationships, and make sure they receive the appropriate screenings."
A multidisciplinary setting in which the patient receives nutrition and activity counseling along with careful titration of GLP-1 RA medications is optimal, he continued, but "a lot of patients won't have access to that. If a dermatologist feels comfortable prescribing GLP-1 RAs, it's probably better for the patients to have access than not to have access."
Gelfand also noted that despite the evidence for independent effects on psoriasis outside of weight loss, GLP-1 RAs are unlikely to be useful for treating people with psoriasis who do not have overweight or obesity because "you don't want people to lose weight if they're not overweight."
In their paper, Issa and colleagues wrote that GLP-1Rs have been detected in the skin of newborn mice and cultured skin cells. In a study of punch biopsies of skin from healthy human volunteers and patients with plaque psoriasis, GLP-1 Rs were expressed in five of six of the psoriasis plaque biopsies, one of six from unaffected psoriatic skin, and one of six from healthy skin. The study authors concluded that the increased presence of the receptors in the psoriasis plaques was most likely due to infiltration with immune cells, offering "a possible explanation for the positive effect of treatment with GLP-1R agonists in patients with psoriasis."
Most of the evidence for wound healing has come from animal studies using the older-generation GLP-1 RAs liraglutide or exendin-4. Suggested mechanisms include anti-inflammatory/pro-healing effects, endothelial protection and angiogenesis, increased endothelial cell proliferation, induced keratinocyte migration, increased vascularity, and dermal/epidermal regeneration. The findings of these and other studies summarized in their paper "suggest that treatment with GLP-1 RAs could have significant applications in wound healing," Issa and colleagues wrote.
With psoriasis, data regarding improvement with GLP-1 RAs is mixed, and much of it comes from case reports. In one systematic review and meta-analysis of four trials of 32 patients with plaque psoriasis and T2D, those treated with liraglutide had significantly lower Psoriasis Area and Severity Index (PASI) scores and fasting plasma glucose, but no significant differences in body mass index (BMI), A1c, or Dermatology Life Quality Index (DLQI).
"This suggests that the role of GLP-1 RAs in improvement of psoriasis was independent of weight loss or diabetic control," Issa and colleagues wrote.
In a prospective study, 12 weeks of 1.8 mg liraglutide treatment in seven patients with psoriasis and T2D resulted in significant reductions in PASI and DLQI scores, and epidermal thickness. There were also significant improvements in glycemic parameters, BMI, lipids, and inflammatory markers.
"We are unable to determine through this study if improvement in psoriasis is due to mechanisms directly related to GLP-1 RAs or through improved blood glucose management and weight loss," Issa and colleagues noted.
However, in an 8-week randomized, placebo-controlled trial of 20 individuals with obesity but normal glycemia and psoriasis, there were no significant differences in PASI, DLQI, or C-reactive protein in those treated with liraglutide vs control individuals, despite significant weight loss and lower total cholesterol. "Given the lack of response in glucose-tolerant patients, this study suggests that the mechanism by which GLP-1 RAs improve psoriasis is indirect and mediated by glycemic control," Issa and his coauthors concluded in their paper.
HS is a chronic inflammatory condition that commonly presents in intertriginous areas as nodules, abscesses, draining sinus tracts, and scarring. Current treatments include oral and topical antibiotics and biologics such as adalimumab, infliximab, and secukinumab.
Issa and colleagues' paper included literature published through May 2024. In October 2024, a systematic review of GLP-1 RA effects in HS revealed that "GLP1 RAs, specifically liraglutide and semaglutide, led to significant reductions in weight and systemic inflammation in HS patients," the review authors wrote. "Notably, improvements in lesion severity and quality of life were reported. The anti-inflammatory effects of GLP1 RAs were attributed to the suppression of key inflammatory pathways," they added.
They concluded, "GLP1 RAs demonstrate significant potential as an adjunct therapy for HS, addressing both the metabolic and inflammatory aspects of the condition. While early results are promising, further research is necessary to determine their long-term efficacy in managing HS."
Issa and colleagues' paper also summarizes reports of cutaneous reactions to GLP-1RAs, such as injection site pruritus and erythema and rash and/or urticaria. Most of these have been reported with the older GLP 1 RAs exenatide and dulaglutide. Injection site nodules were also mostly reported with exenatide. Altered skin sensations including dysesthesia, hyperesthesia, paresthesia, pain, and burning have all been reported with 50 mg weekly oral semaglutide (Rybelsus).
"Moving forward, it is important for clinicians to be aware of the possibility of known or novel injection-site reactions in response to GLP-1 RAs," they wrote.
Overall, Issa said in the interview, the use of GLP 1 RAs in dermatology "is a promising avenue for future research."
Issa has served as a consultant and advisor for Eli Lilly and Company. Gelfand reported having financial relationships with AbbVie, Amgen, Artax Biopharma, BMS, Boehringer Ingelheim, Celldex, Daavlin Company, FIDE, Healio, Inmagene Biopharmaceuticals, Janssen Pharmaceuticals, Leo Pharma Inc, Maui Derm, Moonlake, National Psoriasis Foundation, Neuroderm LTD, Novartis Pharmaceuticals, Oruka Therapeutics, Pfizer, UCB, and Veolia North America.