Key takeaways:

• For years, obesity was treated as a comorbidity of skin disease.
• Evidence suggests obesity is fueling the inflammation causing some dermatologic diseases, and GLP-1s could play a role in treatment.

GLP-1 receptor agonists are best known for treating type 2 diabetes and obesity, yet a growing body of evidence suggests their benefits may extend well beyond metabolic disease to dermatologic indications.

“GLP-1s are the surprise anti-inflammatory that no one saw coming,” Mona Shahriari, MD, FAAD, associate clinical professor of dermatology at Yale University School of Medicine, told Healio. “They do much more than help with weight loss. They also reduce systemic inflammation.”

Image: Jeslaney Rodriguez, MA

Interest in GLP-1s’ dermatologic potential accelerated this year after the landmark TOGETHER-PsO trial showed that combination treatment with tirzepatide (Zepbound, Lilly), a dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonist, and ixekizumab (Taltz, Lilly), an interleukin-17a inhibitor, significantly improved psoriasis outcomes compared with ixekizumab alone.

The new evidence supports what many dermatologists have long suspected: GLP-1s may be a valuable therapeutic tool for treating multiple inflammatory skin diseases, namely psoriasis, psoriatic arthritis and hidradenitis suppurativa.

Benefits independent of weight loss

TOGETHER-PsO — a 52-week, phase 3b, randomized, double-blind, open-label study — demonstrated patients with psoriasis were five times more likely to achieve the multicomponent, primary endpoint of PASI 100 and a 10% or more reduction in body weight by 36 weeks if they received both ixekizumab and tirzepatide, Healio previously reported.

Investigators found 27.1% of participants who received combination therapy, compared with 5.8% of those receiving ixekizumab monotherapy, achieved the primary endpoint by week 36. Notably, 40.6% of patients in the combination group vs. 29% in the monotherapy group achieved complete skin clearance despite not meeting the weight loss target.

“The combination of ixekizumab and tirzepatide is much more effective than ixekizumab alone,” Mark Lebwohl, MD, principal investigator for the TOGETHER-PsO trial, told Healio. “If your most effective [psoriasis] treatments are not working well enough, adding obesity medications may increase the efficacy of those treatments.”

Researchers observed similar results for adults with psoriatic arthritis and obesity participating in the counterpart TOGETHER-PsA. In that study, 31.7% of patients in the combination ixekizumab and tirzepatide group achieved the primary endpoint of a 50% improvement in PsA activity and at least a 10% weight reduction, compared with 0.8% of participants assigned to monotherapy, Healio reported.

Data also suggest GLP-1s may play a significant role in the treatment of HS, a chronic, inflammatory skin condition that causes painful abscesses and tunnels in the skin.

According to a 2025 review published in the Journal of the American Academy of Dermatology, more than 58% of patients saw improvement in their HS after initiating semaglutide (Ozempic/Wegovy, Novo Nordisk), liraglutide or tirzepatide.

“What is interesting for HS is that one study has shown that patients saw improvements in their skin even if they didn’t see significant weight loss,” Steven Daveluy, MD, FAAD, professor of dermatology at Wayne State University, told Healio.

A study published in July in JAMA Dermatology added to the growing evidence, showing that patients with HS treated with GLP-1s had a lower risk for all-cause mortality and major adverse cardiovascular events. This benefit, observed in more than 20,000 patients, was sustained through 2 years.

Treating obesity ‘removes the fuel’

The benefits of GLP-1s in inflammatory skin diseases are thought to arise through two closely interconnected mechanisms: weight loss and anti-inflammation.

“It has been known for a long time that there is a connection between obesity and these skin conditions,” Sara Perkins, MD, associate professor of dermatology at Yale School of Medicine, told Healio. “Most of these patients have overweight or obesity as well as other risk factors such as cardiovascular disease, metabolic syndrome and diabetes.”

According to a study published in the Journal of the European Academy of Dermatology & Venerology, approximately 80% of the 60 million people worldwide with psoriasis have overweight or obesity. According to the Hidradenitis Suppurativa Foundation, obesity is the most common comorbidity linked to HS and is strongly associated with increased disease severity. GLP-1s likely mitigate a key driver of systemic inflammation, and data suggest some benefits may be independent of weight loss.

“For years, we have treated obesity as something that happens to coexist with diseases like psoriasis, but now we know that those fat cells are producing cytokines that fuel the very diseases that we are trying to treat,” Shahriari said. “That changes the conversation.”

According to Shahriari, adipose tissue is not just composed of fat-storing cells — it is an active endocrine organ that produces pro-inflammatory cytokines that contribute to inflammatory skin disease. GLP-1s reduce this inflammatory burden through both weight loss and direct immunomodulatory effects, Shahriari said.

“I like to think of obesity as adding fuel to the inflammatory fire,” Shahriari said. “Obesity does not cause diseases like psoriasis or HS, but it can make them more severe and harder to treat. Treating obesity helps remove the fuel while our targeted therapies put out the fire.”

In the TOGETHER-PsO trial, Shahriari said ixekizumab blocked IL-17a while tirzepatide addressed the metabolic inflammation coming from the adipose tissue.

“By adding this therapy, we went from simply suppressing the immune response to also removing one of the major drivers that kept fueling it,” Shahriari said.

GLP-1s in clinic: ‘Start low and go slow’

Successful use of GLP-1s requires more than simply writing a prescription. Optimal outcomes depend on selecting the right medication, identifying suitable candidates, crafting ideal management strategies and employing appropriate titration schedules, all while keeping safety in mind, according to Shahriari.

GLP-1s that are FDA-approved to treat obesity include:

• liraglutide, a daily injectable;
• orforglipron (Foundayo, Lilly), an oral GLP-1 approved in April for adults with obesity;
• semaglutide, a once-weekly injectable or daily oral medication; and
• tirzepatide, a once-weekly injectable.

Adults who have a BMI of at least 30 or a BMI of 27 to 30 and at least one weight-related health condition are eligible for a GLP-1 prescription, according to the Association of American Medical Colleges. For this reason, Perkins said that only dermatologic patients with a metabolic indication are ideal candidates for concomitant GLP-1 therapy.

“We are not yet at a place where someone with a normal BMI, despite having a dermatologic disease, should also go on this combination treatment,” Perkins said.

If a dermatologist determines their patient could benefit from a GLP-1, Shahriari recommends they monitor them every 4 to 8 weeks, looking for three key changes: weight loss, appetite reduction and skin improvement.

Most patients should lose approximately 0.5% to 1% of their body weight every week, but this may differ from person to person, Shahriari said. This is why it is important not to titrate based solely on scale, according to Shahriari.

“My mantra is to start low and go slow,” Shahriari said. “While I generally like to follow the FDA-approved titration schedule, I do let the patient guide me. If they are tolerating the medicine well but are still hungry and losing weight at an appropriate rate, I increase the dose. If they are experiencing significant gastrointestinal side effects or losing weight too quickly, I’ll stay on the current dose longer.”

If, during a dose escalation transition, a patient begins experiencing too many adverse effects, Shahriari recommends reverting to the lowest effective dose or the last dose that worked well for them.

“This is a marathon, not a sprint,” Shahriari said. “The goal is not to get every patient to that highest dose. It is to find the lowest effective dose that achieves healthy weight loss and improves their inflammatory disease.”

Enlarge Safety, long-term outcomes

Although generally safe, GLP-1s are associated with several adverse events, including gastrointestinal upset, hair loss and facial sagging, also known as “Ozempic face,” according to Daveluy. GLP-1s have a boxed warning for the potential development of thyroid C-cell tumors, making them contraindicated in those with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, according to the FDA.

Daveluy said that for most who are eligible, the benefits outweigh the risks.

“If patients are nervous about side effects but have severe HS, for example, I will tell them that their disease actually increases their risk for the things they are concerned about, such as heart attacks and strokes,” Daveluy said. “While it is reasonable to be concerned about medication side effects, patients should be more concerned with their disease’s comorbidities. I tell them that it is important we get this inflammation under control.”

Shahriari said patients will likely require long-term treatment with GLP-1s to maintain weight loss and disease control.

“Just like we wouldn’t expect hypertension or diabetes to stay controlled after we stop the medication, many patients are going to regain the weight when their GLP-1 therapy is discontinued, and with that, their skin disease usually flares,” Shahriari said. “Most patients will need to stay on a low dose long term.”

Embracing collaborative care

The success of GLP-1s in dermatology has many dermatologists questioning whether they should prescribe the medications or defer to colleagues in obesity medicine.

Perkins said dermatologists should adhere to the latter approach.

“I still lean towards collaborating with my colleagues in primary care and endocrinology because I do think there are important monitoring and diet considerations that I may not be the best person to manage,” Perkins said. “That said, in 5 to 10 years from now, if we have more robust evidence that these medicines, independent of weight loss, are beneficial for inflammatory disease, and we receive guidelines, then I would feel more comfortable prescribing.”

According to Fatima Cody Stanford, MD, MPH, MPA, MBA, MACP, FAAP, FAHA, FAMWA, FTOS, an obesity medicine physician-scientist at Massachusetts General Hospital, the current recommendation for dermatologists with patients who may benefit from a GLP-1 medication is to incorporate the expertise of other specialists.

“While dermatologists are frequently on the front lines of identifying obesity-related comorbidities, including psoriasis, prescribing these medications requires longitudinal management, familiarity with metabolic complications and ongoing monitoring,” Stanford told Healio. “For that reason, in most cases, I recommend a collaborative, multidisciplinary approach where dermatologists screen, initiate the conversation and partner with clinicians experienced in obesity medicine, endocrinology or primary care to initiate and manage medications.”

However, the model does not need to be rigid, Stanford added.

“Dermatologists with appropriate training and infrastructure can play a more direct role, particularly as we move toward more integrated care models,” Stanford said. “The key is ensuring that patients receive comprehensive, safe and evidence-based care rather than siloed treatment.”

Shahriari agreed.

“If you ask me whether GLP-1s belong in the dermatology toolkit, my answer is yes, a hundred times yes,” Shahriari said. “I believe we are just scratching the surface of what these drugs can do, not only in dermatology, but across medicine.”

For more information:

Steven Daveluy, MD, FAAD, is professor and program director of dermatology at Wayne State University, associate editor of JAAD Case Reports and coeditor in chief of the Journal of Integrative Dermatology. Daveluy can be reached on X @SteveDaveluy; Instagram @doctor_beard_md; TikTok @doctor_beard_md.

Mark Lebwohl, MD, is dean for clinical therapeutics, professor and chairman emeritus of the department of dermatology at the Icahn School of Medicine at Mount Sinai. Lebwohl can be reached at lebwohl@aol.com.

Sara Perkins, MD, is associate professor of dermatology at Yale School of Medicine. Perkins can be reached at dermatology@healio.com.

Mona Shahriari, MD, FAAD, is associate clinical professor of dermatology at Yale University School of Medicine, associate director of clinical trials at CCD Research PLLC and founding partner of Central Connecticut Dermatology. Shahriari can be reached on Instagram @persianskindoc.

Fatima Cody Stanford, MD, MPH, MPA, MBA, MACP, FAAP, FAHA, FAMWA, FTOS, is an obesity medicine physician-scientist at Massachusetts General Hospital and associate professor of medicine and pediatrics at Harvard Medical School. Stanford can be reached on Instagram @askdrfatima.