GLP-1 Hidradenitis Suppurativa: Semaglutide and Tirzepatide Evidence in 2026

Twenty patients on weekly tirzepatide, 24 weeks, open label, single arm. 80 percent hit HiSCR. That is the headline from Acosta-Madiedo et al. (2025) in the December 2025 issue of the Journal of Drugs in Dermatology. HiSCR is the standard hidradenitis suppurativa response endpoint: at least a 50 percent reduction in inflammatory lesion count without an increase in abscesses or draining tunnels. Adalimumab, the first and longest-running approved HS biologic, hit HiSCR in roughly 42 to 59 percent of patients in PIONEER I and II at week 12. Secukinumab in SUNSHINE and SUNRISE produced 42 to 46 percent at week 16. Bimekizumab in BE HEARD I and II hit 45 to 54 percent at week 16.

A single Phase 2 open-label proof of concept does not beat any of those trials. It does force a question. A metabolic drug not approved for any dermatology indication, tested at a single center with no placebo arm in 20 patients, produced a response rate at least as high as the three FDA-approved HS biologics produced in their pivotal trials. That observation, paired with four observational cohorts and one large incidence study published between September 2024 and July 2025, is why hidradenitis dermatologists started running the GLP-1 question on consults this year.

This piece walks through what semaglutide and tirzepatide actually did in the published 2024 to 2025 evidence, how the effect sizes compare to existing biologics, what the mechanism likely is, and where this sits for a patient with HS plus obesity considering semaglutide or tirzepatide.

Bottom line: Across four observational cohorts, one incidence cohort, one case report, and one 20-patient open-label proof of concept, semaglutide and tirzepatide produced consistent improvement in HS disease activity, flare frequency, quality of life, and healthcare utilization. The signal is real, the evidence is mostly observational, and the placebo-controlled trial that would settle the magnitude has not been run.

Why HS and obesity track together

Hidradenitis suppurativa is a chronic, recurrent inflammatory disease of the apocrine gland-bearing skin: axillae, groin, inframammary folds, perianal region. Painful nodules become draining sinuses and tunnels. Published prevalence estimates run between 0.05 and 4.1 percent depending on definition and geography, with North American claims data clustering around 0.1 to 1 percent and European cohorts higher.

What makes HS different from most dermatology conditions is how tightly it tracks obesity. A population-based JAAD pediatric analysis showed obesity prevalence of 68.7 percent in pediatric HS patients versus 29.8 percent in non-HS controls, with an adjusted odds ratio for obesity of 2.48. Adult cohorts run higher: 50 to 77 percent obesity prevalence in moderate-to-severe HS. Smoking is the second-strongest environmental signal, and metabolic syndrome shows up roughly twice as often in HS cohorts as in matched non-HS controls.

The biology overlaps. HS shares with obesity a chronic low-grade systemic inflammatory state: elevated IL-1β, TNF-α, IL-17A, and NLRP3 inflammasome activity. Mechanical loading on intertriginous skin from excess adipose tissue compounds the follicular occlusion that initiates HS lesions. Adipokines from visceral fat shift macrophage polarization toward M1, which is the same skewing that drives the IL-17 and IL-1 axis dermatologists target with biologics.

Weight loss alone, achieved any way, blunts HS activity. Bariatric surgery cohorts show flare reduction and modest Hurley stage regression. The question for the past three years has been whether GLP-1 receptor agonists do something on top of, or distinct from, the weight loss.

The semaglutide observational cohorts

Four observational studies in 2024 and 2025 looked specifically at semaglutide in HS patients, with broadly consistent direction of effect.

Lyons, Nathan, Pender et al. (2024) in the British Journal of Dermatology followed 30 patients with obesity and HS who started semaglutide for weight management. Mean patient-reported flare interval lengthened from once every 8.5 weeks to once every 12 weeks. Dermatology Life Quality Index dropped from 13 to 9 on a 30-point scale. About a third of patients had a DLQI reduction of at least 4 points, which exceeds the minimally important difference for the instrument. The signal held whether or not patients were on a concurrent biologic.

Posada Posada, Alora, Lima (2024) in the Journal of the European Academy of Dermatology and Venereology ran a separate retrospective chart review of 45 obese or diabetic HS patients on semaglutide. They reported parallel improvements in DLQI, weight, HbA1c, and HS Physician Global Assessment scores. The design did not allow for inflammatory biomarker tracking, but the direction of the effect matched the Lyons data.

Gupta, Cesar, Micheletti, Fang (2025) at the University of Pennsylvania Department of Dermatology surveyed 22 adults with HS on active GLP-1 RA treatment between January 2019 and August 2024. Mean age 45, 91 percent female, 55 percent Black, mean treatment duration 17 months. The breakdown by molecule: semaglutide 41 percent, tirzepatide 36 percent, dulaglutide 18 percent, liraglutide 5 percent. More than two-thirds reported subjective symptom improvement. The Penn data is useful because it captured a more racially diverse patient population than the European cohorts and showed similar response patterns across multiple GLP-1 molecules.

Hill and Bordeaux (2025) in the Journal of the American Academy of Dermatology took a different angle. Instead of disease severity, they looked at healthcare resource utilization. Using the TriNetX network they identified HS patients on semaglutide and compared HS-related healthcare encounters before and after initiation. The cohort showed reduced HS-related emergency department visits, hospitalizations, and surgical procedures in the post-semaglutide window. That endpoint translates a clinical signal into an economic argument, which is exactly the kind of evidence dermatologists need to justify the off-label conversation with insurers.

The incidence signal

The most quietly important paper in the GLP-1 to HS literature came out of Ching, Guirguis, Iskandar, Tung (2025) in JAAD International. The design was a retrospective cohort study of type 2 diabetes patients in a multi-institutional database. The exposure was GLP-1 receptor agonist initiation. The endpoint was new diagnosis of hidradenitis suppurativa or psoriasis during follow-up.

Patients on GLP-1 RAs had an adjusted odds ratio of 0.61 for incident HS diagnosis, P less than 0.001. The same direction held for psoriasis, with comparable effect size. After adjusting for body weight change, smoking status, and glycemic control, the protective signal persisted.

Two implications. The magnitude (a 39 percent relative reduction in incident HS in diabetic patients) is on par with the strongest signals from immunosuppressive prophylaxis in other autoimmune conditions. And the effect surviving adjustment for weight loss is the strongest piece of evidence to date that GLP-1 RAs do something to HS pathophysiology beyond shrinking adipose tissue. The cohort is observational and channeling bias is impossible to fully exclude, but the size of the dataset and the adjustment matrix make this the most defensible argument for a direct anti-inflammatory mechanism in the GLP-1 to HS literature.

The tirzepatide-specific data

Semaglutide carries most of the published HS evidence. Tirzepatide is the molecule with the cleaner mechanistic story: GLP-1 plus GIP receptor co-agonism, larger weight loss in SURMOUNT, and a more pronounced effect on visceral adiposity. Two papers are doing the lifting.

Chan, Kaur, Kaffenberger (2024) in JAAD Case Reports described a woman in her 20s with 10 years of HS, BMI 41.4, type 2 diabetes, and polycystic ovary syndrome who had cycled through topicals, oral antibiotics, oral contraceptives, spironolactone, oral corticosteroids, adalimumab, and infliximab. She started tirzepatide 2.5 mg weekly for diabetes, titrated to 7.5 mg over three months. DLQI dropped from 14 (significantly affecting her life) to 3 (no effect). Visual analog scale for pain went from 3 to 1. Her HS Physician Global Assessment improved from moderate to mild. Lesion counts dropped from one abscess to zero and four baseline inflammatory nodules to three. She remained on infliximab during the tirzepatide course, so the case cannot isolate the tirzepatide contribution, but the magnitude and timing of the improvement on top of stable biologic therapy was the signal the field cited.

Acosta-Madiedo et al. (2025) in the Journal of Drugs in Dermatology is the closest thing to a prospective trial in the literature. Twenty adults with moderate-to-severe HS received once-weekly tirzepatide, titrated to maximum tolerated dose, for 24 weeks, followed by an 8-week washout. The primary endpoint was HiSCR at week 24. 16 of 20 (80 percent) achieved HiSCR, with P less than 0.00001 against the null of zero response. Secondary endpoints included DLQI, visual analog pain scale, Physician Global Assessment, and the Hospital Anxiety and Depression Scale. All moved in the expected direction. Adherence was high. Some of the benefit persisted through the 8-week washout window, which suggests the effect is not purely pharmacological.

Open label, single arm, n equals 20. The trial cannot answer placebo-controlled efficacy, durability past 32 weeks, or comparative effectiveness against adalimumab or bimekizumab. As a proof of concept, the response rate is high enough to justify the Phase 3 program that has not yet been registered.

The published studies at a glance

Mechanism: weight loss versus direct anti-inflammatory action

Two non-mutually-exclusive mechanisms are on the table.

Weight loss is the obvious one. Reducing adipose tissue lowers systemic IL-6 and TNF-α, reduces leptin and visfatin signaling, and decreases mechanical friction at intertriginous lesion sites. Bariatric surgery cohorts have shown HS improvement in the same direction without any pharmacological anti-inflammatory intervention, so the weight-mediated pathway is established as causal in HS.

Direct anti-inflammatory action is the more interesting one. GLP-1 receptors are expressed on macrophages, dendritic cells, and a subset of CD4-positive T cells. In rodent and human ex-vivo models, GLP-1 receptor agonism reduces NLRP3 inflammasome activation, downregulates IL-1β secretion, and shifts macrophage polarization toward M2. Those are the same inflammatory targets that ustekinumab, secukinumab, and bimekizumab hit through different mechanisms. The Ching incidence data, with the protective signal persisting after adjustment for weight loss, is the cleanest piece of evidence that the direct pathway is contributing.

Tirzepatide adds a GIP component. GIP receptor agonism in obesity reduces visceral adiposity more aggressively than pure GLP-1 agonism, and recent work in murine adipose tissue suggests GIP receptor signaling modulates the macrophage inflammatory milieu. Whether the larger Acosta-Madiedo response rate reflects molecule-specific GIP biology or just deeper weight loss is not yet possible to say.

A practical framework for the GLP-1 question in HS

Note: None of the patient profiles above includes "instead of a biologic." Adalimumab, secukinumab, and bimekizumab carry pivotal trial evidence in HS that no GLP-1 RA has. A GLP-1 RA addition or substitution decision belongs with a treating dermatologist, not with a self-directed protocol.

What this evidence does not change

Three things still matter.

First, no GLP-1 RA is FDA-approved for hidradenitis suppurativa. Adalimumab, secukinumab, and bimekizumab remain the labeled biologic options for moderate-to-severe HS, and the standard of care has not moved. The GLP-1 conversation belongs alongside, not instead of, those agents.

Second, GLP-1 RAs come with class side effects independent of the HS question. Nausea, gastroparesis, pancreatitis signal, gallbladder events, and the 2023 ASA pre-procedural aspiration guidance all still apply. HS patients undergoing deroofing, excision, or laser treatment under sedation are precisely the population that guidance was written for. We cover the procedural risk question in the GLP-1 pancreatitis review and the pre-surgery aspiration guidance article. The gastroparesis evidence review covers the dose-relationship data.

Third, the evidence base is observational. No RCT has been completed with HiSCR or IHS4 as the primary endpoint. Open-label proof of concept is hypothesis-generating, not confirmatory. The honest answer to "does semaglutide treat HS" is "probably contributes useful effect, magnitude unknown, mechanism partly weight-mediated and partly direct, do not stop a working biologic to find out."

The trials that would settle this

The Phase 2 and Phase 3 pipeline for HS in 2026 is dominated by IL-17 and IL-1 axis biologics. No registered Phase 3 of semaglutide or tirzepatide for HS exists at the time of writing. What will likely come first is an investigator-initiated multi-center RCT of tirzepatide following the Acosta-Madiedo proof of concept, with HiSCR or IHS4-55 as the primary endpoint and a placebo arm. The 2025 systematic reviews in the American Journal of Clinical Dermatology and Current Dermatology Reports both flagged the absence of an RCT as the single largest gap in the literature.

Closely related work on the metabolic-inflammatory axis is moving in parallel. The GLP-1 inflammatory bowel disease evidence review covers the same biology in a different organ system. The GLP-1 PCOS evidence article overlaps significantly with HS in the obese hyperandrogenic female phenotype, which represents a meaningful fraction of the HS population. The broader cardiometabolic case for the class sits in the SELECT trial cardiovascular review.

For research-only sourcing of injectable semaglutide or tirzepatide, Ascension Peptides carries both with code ENHANCED for 50 percent off. Oral semaglutide and the next-generation oral GLP-1 candidates relevant to the HS question are catalogued at Limitless Biotech with code ENHANCED.

Bottom line: Across four observational cohorts, one large incidence study, one case report, and one 20-patient open-label proof of concept, semaglutide and tirzepatide produced consistent improvement in HS disease activity, flare frequency, quality of life, and healthcare utilization. The Ching 2025 incidence cohort suggests a 39 percent relative reduction in incident HS diagnosis in diabetic GLP-1 RA users that survives adjustment for weight loss. The Acosta-Madiedo 2025 open-label trial reported 80 percent HiSCR with weekly tirzepatide at 24 weeks. The evidence supports adding a GLP-1 RA to the metabolic plan for moderate-to-severe HS patients with obesity or type 2 diabetes, not replacing adalimumab, secukinumab, or bimekizumab. The placebo-controlled trial that would settle the magnitude has not been run.

---

This article is for educational and research purposes only and is not medical advice. No GLP-1 receptor agonist (semaglutide, tirzepatide, dulaglutide, liraglutide, or any next-generation candidate) is FDA-approved for hidradenitis suppurativa, psoriasis, or any dermatological indication. The data summarized above is overwhelmingly observational, drawn from retrospective cohorts, cross-sectional surveys, a single case report, and one 20-patient single-arm open-label proof-of-concept study. No randomized placebo-controlled trial has been completed with HiSCR or IHS4 as the primary endpoint. The 80 percent HiSCR response rate in the Acosta-Madiedo 2025 tirzepatide trial cannot be directly compared to the HiSCR rates reported in the PIONEER, SUNSHINE, SUNRISE, or BE HEARD pivotal trials because the trial designs, patient populations, and placebo controls differ in ways that matter for interpretation. Adalimumab, secukinumab, and bimekizumab remain the FDA-labeled biologic options for moderate-to-severe HS. GLP-1 receptor agonists carry class side effects including nausea, vomiting, delayed gastric emptying, pancreatitis signal, gallbladder events, and pre-procedural aspiration risk that are independent of the HS question and that may matter more for HS patients undergoing frequent dermatological surgeries. Do not start, switch, or stop any GLP-1 receptor agonist, HS biologic, antibiotic, or topical agent on the basis of this article. Consult a dermatologist or qualified prescribing clinician about your individual circumstances before acting on any information here.