Clinical and mechanistic effects of GLP-1 receptor agonists in hidradenitis suppurativa and comorbidities

Abstract

Hidradenitis suppurativa (HS) is a painful inflammatory skin disease within the pilosebaceous unit associated with numerous comorbidities, including obesity type-2-diabetes (T2DM), and a general meta-inflammatory state. This narrative review explores the therapeutic potential of GLP-1-receptor-agonists (GLP-1RAs) in treating HS by analyzing mechanisms of action and clinical outcomes. Based on a literature search, encompassing 12 cohorts and 4 case-based reports, current evidence demonstrates significant improvements in both clinical and patient-reported outcomes in patients with HS treated with GLP-1RAs. Treatment consistently resulted in reduced body mass index (BMI) and disease activity, measured by Hurley-staging and the number of nodules and abscesses. Patients across studies experienced fewer flares and less pain, supporting improvements in dermatology quality of life (DLQI) scores. Studies observed reductions in systemic inflammatory markers and improved glycemic control. The beneficial effects of GLP-1RAs in HS are attributed to the reduction in mechanical friction and metabolic improvements from weight loss. Suggestively, concurrent and direct anti-inflammatory mechanisms, including inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway and modulation of cytokines, occur independently of weight-reduction. Results from cohorts and cases supported this theory, showing significant improvements in HS and metabolic markers independent of weight-related outcomes. Four supplementary cohorts found GLP-1RAs beneficial for cardiovascular comorbidities in patients with HS. Additionally, studies suggest that GLP-1RAs enhance the efficacy of biologic therapies used for HS and reduce the need for adjunctive treatment. In conclusion, GLP-1RAs represent a promising pleiotropic treatment within a multimodal therapy strategy for HS and comorbidities.

Background

Hidradenitis suppurativa (HS) is a painful, chronic inflammatory skin disease involving the pilosebaceous unit and characterized by nodules, abscesses, draining tunnels, and scarring. Lesions primarily arise in intertriginous areas such as the axillae, groin, and gluteal regions, and the disease typically debuts after puberty, with a female predominance and an estimated global prevalence of 1%.^1,2 Increased body mass index (BMI) has been associated with worsened disease progression and a lower quality of life in patients with HS. ³ Additionally, HS is heavily associated with a series of comorbidities, including inflammatory diseases and metabolic diseases such as type 2 diabetes mellitus (T2DM) and obesity.^4,5

The exact pathogenesis of HS is not completely understood but is thought to develop from a meta-inflammatory state affecting the terminal hair follicles, causing infundibular hyperkeratosis and resulting in plugging and rupture of the follicles. Cell damage and bacteria trigger the induction of an intense inflammatory immune response, clinically presenting as inflamed nodules and abscesses.^1,6 More specifically, the release of pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) from damaged skin cells drives several immunologic pathways through Toll-like-receptors (TLRs) with responses mediated by T-helper cells; Th1 and Th17, through the recruitment of neutrophils, macrophages, B-cells and activation of the inflammasome with an increase in interleukin-1β (IL-1β) production.^1,7,8

Similar to HS pathogenesis, treatment is generally complex and often requires a combination of different modalities depending on the severity and phenotype.^9,10 For mild HS, topicals such as clindamycin 1% or topical peels often serve as first-line treatment. For systemic treatment, antibiotics such as tetracyclines are often the first choice, while a combination of rifampicin and clindamycin is commonly used for moderate to severe disease. In treating refractory or more severe HS, biologics represent a cornerstone, targeting the above-mentioned immune responses.^9,10 Biologics such as adalimumab (anti-TNF- α), secukinumab (anti-IL17A), and bimekizumab (anti-IL17A/F) are approved for HS. Other agents, such as infliximab (anti-TNF- α) and ustekinumab (IL-12/23) are often used as off-label treatments. ¹⁰ Emerging small-molecule therapies such as povorcitinib and upadacitinib (JAK1 inhibitors) have also shown promising results in clinical trials. ¹⁰

Surgeries are often necessary when the disease has led to irreversible tissue destruction, which cannot be resolved with medication. Methods include deroofing, wide local excision, and CO2-laser.^9,10

Large weight loss interventions, particularly bariatric surgery, are associated with improvements in disease severity.^9,10 Additionally, emerging studies show promising results in the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) traditionally prescribed for obesity and T2DM, in treating both HS and comorbidities.^4,11GLP-1RAs induce both mechanical and systemic improvements through weight reduction, addressing the metabolic drivers in a manner similar to effects seen following bariatric surgery. ¹² Moreover, they show promise in their ability to both mimic and synergistically enhance the immunomodulatory effects of biological and small-molecule therapies by theoretically suppressing pro-inflammatory cytokines.^13,14 This narrative review aims to explore the potential therapeutic role of GLP-1RAs in HS by examining their mechanistic pathways potentially relevant for HS, summarizing current clinical evidence, and evaluating the objective patient outcomes.

Methods

This review was guided by the Scale for the Assessment of narrative review articles (SANRA). ¹⁵ A structured approach was applied to identify relevant literature (Supplementary Figure 1). PubMed and Embase were searched on 8 November 2025 and 23 November 2025, respectively, using key terms related to “hidradenitis suppurativa” and “acne inversa” combined with “GLP-1” or “GLP-1 agonists” and specific agents, including “semaglutide”, “liraglutide”, “dulaglutide”, and “tirzepatide” (Supplementary Table 1). Clinical studies were included if they reported original HS-specific outcomes following the use of GLP-1RAs. Records without an HS population, GLP-1RA exposure, or original clinical outcome data were excluded. The combined search strategy yielded 85 unique records. Following screening, 12 cohorts and 4 case-based reports were included to evaluate GLP-1RA use in patients with HS, with the primary outcomes including weight loss, disease activity, and inflammatory markers. Secondary outcomes addressing cardiometabolic effects were reported in 4 included cohorts. Study quality was assessed using design-appropriate tools to contextualize the strength of the presented clinical evidence (Supplementary Table 2). Additional literature was included to contextualize the proposed mechanisms of GLP-1RAs in HS.

Obesity and meta-inflammation in HS

Genetics and lifestyle factors, including smoking and obesity, are assumed to be the main pathophysiological drivers of HS.^6,12 An elevated BMI is an independent indicator of severe and persistent HS. Additionally, studies find that patients with HS combined with a higher BMI generally experience worse disease outcomes and a lower quality of life.^12,16 Previously, weight loss and bariatric surgery have been strongly associated with HS regression.^4,11 Dysfunctional visceral adipose tissue in patients with obesity is suggested to promote low-grade systemic inflammation by the secretion of proinflammatory adipocytokines activating signaling pathways such as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). ¹² This systemic inflammation is believed to exacerbate or even initiate the local inflammatory processes within the pilosebaceous unit where proinflammatory cytokines; IL-1β, IL-17, IL-23, TNF-α and lymphocyte infiltration promote follicular rupture and local tissue destruction.^6,12 Mechanical friction and irritation in intertriginous skin areas, exacerbated by increased peripheral fat distribution, further contribute to the inflammatory condition. ¹² (Figure 1).

Figure 1.

Obesity, metabolic dysfunction, and inflammation in hidradenitis suppurativa: Obesity may contribute to hidradenitis suppurativa (HS) through mechanical and systemic mechanisms. Increased adiposity can promote friction in intertriginous skin areas, whereas dysfunctional visceral adipose tissue may sustain chronic low-grade inflammation. This meta-inflammatory state is associated with adipokine dysregulation, insulin resistance, and activation of inflammatory pathways, including NF-κB signaling. Together, these processes may increase pro-inflammatory cytokines, such as IL-1β, IL-17, IL-23, and TNF-α, and thereby contribute to follicular occlusion, follicular rupture, immune-cell recruitment, abscess formation, and progressive tissue damage in HS.

Metabolic syndrome and comorbidities in HS

Laboratory studies have supported systemic inflammation and metabolic involvement in HS by showing elevated levels of associated markers of metabolic dysfunction in skin samples from patients with HS who had a BMI greater than 30 kg/m². These skin samples also contained increased expression of the key inflammatory cytokine receptor, interleukin-17 receptor (IL-17R), involved in both HS and systemic inflammation. ¹⁷ HS is also associated with raised levels of leptin, resistin, and visfatin, together with low adiponectin, a pattern that is similar to the adipokine profile seen with metabolic syndrome. ¹² Clinical studies support this connection, showing a particularly high prevalence of metabolic comorbidities in patients with HS, including obesity, T2DM, hypertension, dyslipidemia, and metabolic syndrome. ⁴ Additionally, patients with HS exhibit elevated rates of other comorbidities including increased cardiovascular disease, immune-mediated diseases, and psychiatric disorders. More recent studies have also reported associations with asthma, chronic kidney disease, thyroid disease, and sexual dysfunction, supporting the substantial systemic involvement and complexity in HS pathogenesis.^4,5

Endocrine and metabolic effects of GLP-1RAs

The therapeutic effects of GLP-1RAs include reduced triglycerides, low-density lipoprotein, cholesterol, and reduced fat deposition in the liver and visceral compartments, promoting overall metabolic health. ¹⁸ GLP-1 RAs modulate brain regions controlling appetite and regulate hunger, satiety, and energy expenditure through leptin and ghrelin signaling pathways, contributing to weight loss. ¹⁸ Glycemic control is improved by GLP-1 RAs through enhancement of glucose-dependent insulin secretion in pancreatic β-cells, reduction of glucagon release from pancreatic α-cells, delay of gastric emptying, and regulation of gut hormones, including Peptide YY (PYY), Cholecystokinin (CCK) and Glucose-dependent Insulinotropic Polypeptide (GIP). ¹⁸ Dual and tri-analogues co-targeting these pancreatic and intestinal hormones are on the rise, especially Gastric Inhibitory Polypeptide-Receptor Agonists (GIP-RAs) and Glucagon-Receptor Agonists (GCG-RAs). While GIP modulates both insulin and fat metabolism, glucagon agonism might increase energy usage and fat catabolism. ¹⁸ These endocrine pathways exhibit multiple effects in numerous organ systems including the heart, liver, kidneys, and adipose tissue. ¹⁹ Tirzepatide is a dual-agonist analogue (GIP/GLP-1RA) that is already approved for the treatment of obesity and T2DM. In addition, several novel dual-agonists combining GLP-1RA and glucagon receptor agonism (GLP-1RA/GCG-RA), as well as tri-agonists targeting GIP, GLP-1, and glucagon receptors (GIP-RA/GLP-1RA/GCG-RA), are currently under development. Five head-to-head clinical trials (SURPASS 1-5) have compared tirzepatide to semaglutide. Results showed that tirzepatide groups reached significantly greater reductions in both hemoglobin A1c (HbA1c) and body weight compared to semaglutide groups. ²⁰ Retatrutide (GIP/GLP-1/glucagon) is still undergoing phase 2 trials, showing an even greater potential of weight reduction. ²¹

Anti-inflammatory mechanisms of GLP-1RAs

GLP-1 RAs are hypothesized to exert a range of anti-inflammatory and regenerative effects relevant to skin health and healing. ¹³ The possible anti-inflammatory mechanism of GLP-1RAs involves inhibition of the NF-κB signaling pathway, leading to reduced adipose tissue inflammation and decreased expression of pro-inflammatory cytokines; IL-1β, IL-6, IL-17, and TNF-α, etc. Paralleling mechanisms observed with biologic agents used in HS therapy.^13,14 Moreover, GLP-1 RAs enhance endothelial function via the nitric oxide pathway by reducing the production of Reactive Oxygen Species (ROS) and upregulating endogenous antioxidant enzymes such as Superoxide dismutase (SOD) and catalase, thereby promoting wound repair and restoration of the skin barrier.^13,18 Concurrent weight loss further inhibits metabolic dysfunction and normalizes adipokine dysregulation in leptin, resistin, visfatin and adiponectin, resulting in decreased systemic inflammation. ¹² Additionally, reduced mechanical stress and friction from skin folds contribute to fewer inflammatory responses. ⁶ (Figure 2).

Figure 2.

Proposed mechanisms of GLP-1 receptor agonists in hidradenitis suppurativa and associated comorbidities: GLP-1 receptor agonists (GLP-1RAs) may improve hidradenitis suppurativa (HS) through several complementary mechanisms. Weight reduction may reduce mechanical friction, improve insulin resistance, and attenuate adipose tissue-driven systemic inflammation. GLP-1RAs may also exert direct anti-inflammatory effects by modulating NF-κB signaling, oxidative stress, endothelial function, adipokine balance, and pro-inflammatory cytokines, including IL-1β, IL-6, IL-17, and TNF-α. These effects may contribute to reduced HS disease activity, improved metabolic control, and lower cardiometabolic risk.

Regenerative and immunomodulatory mechanisms of GLP-1RAs

Studies suggest that GLP-1RAs may promote keratinocyte migration, cohesion, and proliferation, thereby accelerating wound healing through the phosphoinositide 3-kinase (PI3K)/Akt (protein kinase B, PKB) pathway. In keratinocytes, GLP-1RAs further inhibit inflammatory responses via AMP-activated protein kinase (AMPK). ¹³ Treatment with semaglutide has been shown to upregulate key growth factors such as epidermal growth factor (EGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF) which are essential for tissue repair, extracellular matrix remodeling, and angiogenesis. Additionally, GLP-1RAs inhibit the activity of matrix metalloproteinases such as MMP3 and MMP9, thereby limiting connective tissue degradation.^13,22 Furthermore, treatment stimulates the synthesis of several collagens: Type I, III, IV, and VI, supporting structural regeneration and integrity. ²² GLP-1RAs are also possibly involved in regulating immune-cell activity through several complementary pathways. They promote polarization of M2 macrophages, characterized by anti-inflammatory cytokine production and enhanced tissue repair.^13,23 Moreover, GLP-1RAs inhibit chemokine-driven migration of lymphocytes, thereby reducing inflammatory cell infiltration in the skin. ¹³ In psoriasis, GLP-1RAs contribute to the redistribution of invariant natural killer T-cells (iNKT-cells) from skin lesions back into circulation, leading to a decrease in local pro-inflammatory cytokines.^13,24

GLP-1RAs and cardiovascular effects

Semaglutide has recently been approved to reduce the risk of cardiovascular events in patients with T2DM and established cardiovascular disease. ¹⁹ The cardiovascular effects of GLP-1RAs potentially arise through both systemic metabolic improvements and direct intracellular mechanisms. ¹⁸ Improvements in lipid profile, triglycerides, and low-density lipoprotein (LDL) further support their role in promoting general cardiovascular health. ¹⁸ Moreover, GLP-1RAs facilitate reductions in visceral adiposity, contributing to reduced cardiovascular risk. ¹⁸ Studies on exenatide have demonstrated increased atrial contractility in isolated human myocardium, potentially through modulation of calcium release and cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathways. ¹⁹ Additionally, exenatide has been shown to prevent atherosclerosis by inhibiting fatty acid metabolism and the conversion of macrophages into foam cells. ¹⁹ It also exerts protective and anti-aging effects on vascular smooth muscle cells (VSMCs) by reducing oxidative stress and cellular senescence. ¹⁹

Clinical evidence: GLP-1RAs in HS management

Treatment of comorbidities such as T2DM and obesity has demonstrated beneficial effects in the management of HS.^4,25 Recent studies further suggest that GLP-1RAs may exert a protective effect against the development and progression of HS.

In a retrospective cohort study by Ching et al. (2025) which included 601 patients with HS and 1,601 with psoriasis, individuals with T2DM treated with GLP-1RAs were significantly less likely to receive a future diagnosis of both HS and psoriasis. This protective association was independent of weight loss, smoking status, or glycemic control, indicating an effect that was independent of traditional metabolic improvements. ²⁶

Similarly, Krajewski et al. (2024) reviewed 25 studies on liraglutide and semaglutide in patients with HS and reported reductions in lesion severity, systemic inflammation, body weight and blood glucose, as well as improvements in insulin sensitivity and Dermatology Life Quality Index (DLQI). The authors highlighted the therapeutic potential of early GLP-1RA intervention in delaying and reducing the need for biologic therapy, potentially achieving a synergistic effect when combined with traditional biologics. ¹⁴

In a systematic review, Birda et al. (2026) analyzed 33 studies investigating the efficacy and safety of GLP-1RAs in patients with immune-mediated inflammatory diseases (IMIDs) including inflammatory bowel disease (IBD), multiple sclerosis (MS), and HS. Treatment with liraglutide was associated with reduced Hurley stage, DLQI, lower C-reactive protein (CRP), and a reduction in pain (VAS-score). Improvements in depressive symptoms (BDI-score) were also observed among patients with HS. Across IMIDs, GLP-1RAs promoted weight loss, glycemic control (HbA1c), and lipid-control, while demonstrating a favorable safety profile with no increase in disease flares. ²⁷

Finally, Tassavor et al. (2025) reviewed 21 studies on GLP-1RAs and identified clinical benefits across several skin disorders, particularly in patients with HS and concurrent obesity or T2DM. Among these, eight studies focused on psoriasis and six on HS, with treatment leading to reduced symptom burden, drainage and flare frequency, pain (VAS-score), and improved DLQI. HS cohorts demonstrated a decrease in the need for antibiotics, steroids, and hospital visits. Benefits were most pronounced in patients with metabolic comorbidities, and no cutaneous adverse effects were reported. ¹³

GLP-1RAs and hidradenitis suppurativa: Cohorts and cases

From this literature review, 16 studies were identified as reporting primary outcomes related to (1) weight loss, (2) disease activity, and (3) serological markers. The evidence base included five retrospective cohort studies comprising a total of 239 patients with HS, three prospective cohort studies totaling 58 patients with HS (although a large portion of patients in two of these, did not receive GLP-1RAs due to insurance issues^28,29) and four single case reports.

Females constituted the majority of participants across all included studies, with mean ages ranging from 36 to 46 years in cohort studies and from 19 to 31 years in case reports. The prevalence of T2DM was high in most cohorts. In Gouvrion et al. (2025), all 66 patients had obesity, and 86% had T2DM. ³⁰ Similarly, Romanelli et al. (2025) included 25 patients with obesity, of whom three patients also had diabetes, and six patients had pre-diabetes. ²⁸ Lyons et al. (2024) reported 30 patients with obesity; two were diabetic, two had IBD, and two patients also had polycystic ovary syndrome (PCOS). ³¹ In Nicolau et al. (2024) among 14 patients with obesity and HS, six patients also had hypertension, five patients had dyslipidemia, two patients had depression, two patients had sleep apnea, nine patients had “emotional eating” and four patients had binge eating disorder. ³² In Posada et al. (2025) which included 45 patients with HS treated with semaglutide, the most significant predictor of response was higher drug doses. Additionally, there was a tendency for men and current smokers to respond better to treatment, even though the findings did not reach statistical significance. ³³ Many participants had previously received multiple systemic therapies including; biologics (adalimumab, infliximab), long-term antibiotics (rifampicin/clindamycin) and hormonal agents (spironolactone and finasteride).^34–36GLP-1RAs were typically administered as adjuvant treatment. In Lyons et al. (2024), the mean duration of prior HS treatment before semaglutide was 14.9 months, and common concurrent treatments included metformin (63%), adalimumab, brodalumab, and lymecycline.^35,37 Most patients were classified as Hurley stage 2 or 3. Affected sites predominantly included intertriginous areas.^6,32,38 DLQI was consistently high, indicating severe impairment in quality of life.^35,36 Smoking emerged as a frequent lifestyle factor across studies. In the Rames et al. (2025) case series, 71% of patients were active smokers, ³⁹ while Lyons et al. (2024) reported 12 active smokers and 10 former smokers; equating to a 73% lifetime smoking prevalence. ³⁷ Nicotine exposure was discussed as a potential contributor to HS pathogenesis by stimulating epidermal hyperplasia and altering immune responses. ³⁷

Outcomes: Weight loss and BMI reduction

Across studies, the use of GLP-1RAs in patients with HS and obesity consistently demonstrated significant reductions in body weight, BMI, and waist circumference in both cohorts and case reports. Nicolau et al. (2024), in a prospective study of 14 patients with HS treated with liraglutide 3 mg daily combined with a 500-calorie daily deficit and 50 min of aerobic exercise weekly, reported a significant decrease in BMI from 39.3 to 35.6 kg/m² and a reduction in waist circumference from 121.3 cm to 110.6 cm after 3 months. ³¹ Similarly, Gouvrion et al. (2025), a retrospective multicenter cohort study including 66 patients with HS receiving various GLP-1RAs, showed a mean BMI decrease from 39.4 to 37.2 kg/m². ³⁰ Romanelli et al. (2025), a prospective cohort of 25 patients with HS, reported a mean weight loss of 9.1 kg over 19.5 weeks, although only 44% of the participants received liraglutide due to insurance issues. ²⁸ Comparable outcomes were documented in single-patient case reports. In one case by Khandalavala et al. (2017), a 19-year-old female with HS and obesity achieved a weight reduction of 18 kg (19% of body weight) following liraglutide treatment for 6 months. Although weight loss was not fully maintained, the patient’s HS remained in clinical remission, suggesting a potential direct anti-inflammatory effect of GLP-1RAs. ³⁸

Outcomes: Disease activity and clinical severity

Across studies, Hurley staging, Hidradenitis Suppurativa Physician Global Assessment (HS-PGA), Hidradenitis Suppurativa Clinical Response (HiSCR) and the number of nodules and abscesses (AN count) were commonly used to evaluate HS disease activity, while DLQI and Numeric Rating Scale (NRS)/Visual Analogue Scale (VAS) pain scores were central patient-reported outcomes. Gouvrion et al. (2025) evaluated patients with HS (median BMI 39.4 kg/m²; 86% with T2DM) treated with GLP-1RAs. At the 6-month follow-up, 54% achieved a ≥1-point reduction in HS-PGA, alongside significant decreases in flare frequency, NRS pain, NRS suppuration, and DLQI. Notably, improvements remained significant even in patients (n=34) whose treatment had been unchanged for 12 months prior. ³⁰ Encarnacion et al. (2025) analyzed 67 patients with HS (BMI ≥ 27 kg/m² and ≥ 2 doctors’ appointments); 64.2% showed clinical improvements based on provider or patient reports, though no changes in Hurley stage were observed. ⁴⁰ Nicolau et al. (2024) treated 14 patients with obesity and HS with liraglutide 3 mg for 3 months, observing a significant reduction in mean Hurley stage (2.6 → 1.1), VAS pain (5.6 → 3.2), and DLQI (12.3 → 9.7). ³¹ In a case series by Rames et al. (2025) patients (four men, three women, 71% smokers) received different GLP-1RAs. Four received dulaglutide, one received liraglutide, one received tirzepatide, and one received semaglutide for a mean of 329.5 days. ³⁹ Three patients demonstrated measurable improvement: Patient 1 (dulaglutide): Hurley stage decreased from 3 to 2, and affected areas were reduced from 4 to 2 (after concurrent bariatric surgery). Patient 2 (dulaglutide): Hurley stage decreased from 3 to 2. Patient 3 (tirzepatide): Hurley stage decreased from 2 to 1 (concurrent secukinumab therapy).

Several individual case reports described similar clinical improvements. Chan et al. (2024) reported a woman in her twenties (BMI 41.3 kg/m², 10-year HS history) treated with tirzepatide while on infliximab, achieving a reduction in HS-PGA from 3 to 2 and a DLQI improvement from 14 to 3. ³⁴ Drumm et al. (2023) described a 21-year-old (BMI 33 kg/m², Hurley 2) treated with semaglutide. After 6 weeks, disease severity improved, DLQI decreased, and the patient no longer needed daily narcotic analgesia. ³⁶ In Jennings et al. (2017) a 31-year-old female smoker (BMI 45.3 kg/m², Hurley 2) presented with HS affecting the sub-mammary area, abdomen, groin, and upper thighs. After treatment with liraglutide, HS-PGA decreased from 4 to 1 and DLQI from 24 to 14; HS remained well-controlled, despite previous resistance to adalimumab, dapsone, metformin, and several antibiotics, and the patients had previously required daily pain medication. ³⁵ Khandalavala (2017) reported a 19-year-old female (BMI 37 kg/m², 8-year HS history, Hurley 3) with HS, PCOS, fatty liver, anemia, and acne treated with liraglutide combined with metformin, dapsone, finasteride, and contraceptives. Additionally, she was put on an aggressive low-carbohydrate diet. The patient experienced complete healing of the axillary regions. Previously, her disease was resistant to several treatments, including several surgeries. ³⁸

Outcomes: Inflammatory and metabolic markers

Several studies assessed inflammatory and metabolic markers to evaluate the systemic effects of GLP-1RA treatment in HS. In Nicolau et al. (2024) months of liraglutide treatment resulted in a significant decrease in CRP, homocysteine, plasma-cortisol, and insulin levels. Similarly, Lyons et al. (2024) reported a significant decrease in HbA1c following semaglutide treatment. In a single case, Khandalavala et al. (2017) reported that multimodal treatment including liraglutide showed extensive improvements over 3 years in white blood cell count, hemoglobin, and liver enzyme profiles. ³⁸ In another single case by Chan et al. (2024) treatment with tirzepatide resulted in an extensive reduction in HbA1c and triglycerides over 3 months. ³⁴ Killion et al. (2025) (n = 69), the measured parameters included neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammatory index (SII), and systemic inflammation response index (SIRI). NLR decreased from 2.42 to 2.33 and SII from 756 to 705. Paradoxically, SIRI increased from 1.48 to 1.57, although results did not reach statistical significance; the overall trend suggested attenuation of systemic inflammation. ⁴¹ In Romanelli et al. (2025), the IDEOM Musculoskeletal Questionnaire (MSK-Q), traditionally used in psoriasis, was applied to patients with HS (n=25) treated with GLP-1RAs. ²⁹ At baseline, the mean impact score was measured at 5.8 ± 3.5 (on a scale up to 10), reflecting a substantial musculoskeletal symptom burden. Among patients who completed follow-up, improvements across most MSK-Q items were observed, suggesting the potential benefit of GLP-1RA therapy for systemic musculoskeletal inflammation associated with HS. ²⁹ (Table 1, Table 2).

Table 1.

Clinical Cohort studies of GLP-1RAs in Hidradenitis Suppurativa.

Study	Population	Mean Age	Baseline BMI	Hurley stage	GLP-1RA regimen	Concomitant treatments	Key Outcomes
Retrospective cohort 37	30 patients with HS	42 yrs.	NA	III(n=11)	Semaglutide 0.8 mg weekly, 8.2 months	Adalimumab, infliximab, brodalumab, metformin, spironolactone	Weight: -6.1 kg.
				II(n =15)			Flares: reduced. DLQI: 13 → 9
				I (n=1)			HbA1c: 39.3 → 36.6 mmol·mol -1 .
							CRP: 7.8 → 6.9 mg·L -1 .
Retrospective cohort 41	69 patients with HS	41.8 yrs.	NA	III(n=10)	Semaglutide 1 mg weekly, 17.1 months	Adalimumab, infliximab, brodalumab, secukinumab, metformin, antibiotics, spironolactone	NLR: 2.42 → 2.33
				II(n =54)			SII: reduced.
				I (n=1)			SIRI: 1.48 → 1.57.
Retrospective multicenter cohort 30	66 patients with HS	46 yrs.	39.4 kg/m2	III(n=15)	Semaglutide (n=48), dulaglutide (n=13), liraglutide (n=5), 6 months	NA	BMI: -2.7 kg/m 2 .
				II(n =21)			HS- PGA: reduced ≥ 1 in 54%.
				I (n=30)			Flares: reduced.
							NRS-Pain: reduced. DLQI: improved.
Retrospective cohort 40	67 patients with HS	NA	>_27 kg/m2	NA	GLP-1RAs (unspecified), 4 years	NA	Weight: -4.5kg in improving patients.
							Weight: -0.09kg in stable/worsening patients. Hurley stage: no change
							Pain: reduced. Lesions: reduced.
							Drainage: reduced. Flares: reduced.
Case series 39	7 patients with HS	46 yrs.	45.5 kg/m2<	NA	Dulaglutide (n=4), semaglutide (n=1), liraglutide (n=1), tirzepatide (n=1); mean 329.5 days	Bariatric surgery secukinumab	Objectives: improved (n=3).
							Hurley stage: 3 → 2.
							HS sites: 4 → 2.
							Inflammatory markers: reduced (n=1).
Prospective cohort 28	25 patients with HS	36 yrs.	39.6 kg/m2	NA	GLP-1RAs (44% received therapy), 19.5 weeks	NA	Weight: -9.1 kg
							HiSCR: improved Abscess count: reduced. Nodule counts: reduced.
							NRS-pain: reduced. Cholesterol: reduced. Lipoprotein A: reduced.
							Apolipoprotein B: reduced. HbA1c: reduced. MSK-Q: improved.
Prospective cohort28,29	19 patients with HS	34 yrs.	39.53 kg/m2	NA	GLP-1RAs (47.4% received therapy), 16 weeks	NA	Weight: -6.8 kg
							Abscess count: reduced.
							Nodule counts:reduced.
							NRS-pain: reduced. Cholesterol: reduced. Lipoprotein A: reduced.
							Apolipoprotein B: reduced.
							HbA1c: reduced. MSK-Q: improved.
Prospective cohort 31	14 patients with HS	46.1 yrs.	NA	NA	Liraglutide up to 3 mg daily, 3 months	Caloric restriction, exercise, biological agents topical antibiotics	BMI: -3.7 kg/m 2 .
							Waist circumference: 121.3 →110.6 cm. Hurley stage: 2.6 → 1.1.
							DLQI: 12.3 → 9.7. CRP: 4.5 → 3 mg/L. Homocysteine: 16.2 →13.3 mol/L.
							Cortisol: 15.9 →12.6 ug/dL.

Table 2.

Clinical Case studies of GLP-1RAs in Hidradenitis Suppurativa.

Study	Patient	Earlier treatment	GLP-1R Regimen	Outcome
Case report 34	BMI 41.36 kg/m2, PCOS, T2DM and Obesity	Antibiotics, Oral contraceptives, Spironolactone, Oral corticosteroids, Adalimumab, infliximab	Tirzepatide 2.5–7.5 mg weekly for 3 months	Weight: -16%.
				BMI: -7.63 kg/m2.
				DLQI: 14 → 3.
				HS- PGA: 3 → 2.
				VAS-pain: 3 → 1.
				Lesion count: 5 → 3.
				Fasting blood-sugar: 179 → 95 mg/dL.
				Random blood sugar: 220 → 108 mg/dL.
				HbA1c: 10.1 → 5.4%.
				Triglyceride: 233 → 139 mg/dL.
Case report 36	21-year-old woman, BMI 33 kg/m2, Hurley SII	Antibiotics, Metformin, Spironolactone and Adalimumab	Semaglutide 1 mg weekly, 6 months	Weight: -24 kg.
				Flares: reduced.
				Clinical symptoms: improved.
				Subjective symptoms improved.
Case report 35	31-year-old woman, BMI 45 kg/m2, smoker, Hurley SII	Rifampicin-Clindamycin, Metformin, Spironolactone, Adalimumab, Etanercept and Dapsone	Liraglutide 0.6 mg daily, 6 months	Weight: -6.5 kg
				HS: improved
				DLQI: reduced
				Analgesia: reduced
				CRP: unchanged
Case report 38	19-year-old woman, BMI 37 kg/m2, POD, acne, obesity, pre-diabetes. Hurley SII	Oral and intravenous antibiotics, numerous surgeries, Isotretinoin, Metformin, Contraceptives	Liraglutide 0.6 mg daily, 3 years	Weight: -19%
				Weight: increased later.
				Flares: reduced.
				Abscess: improved.
				New lesions: reduced.
				Lesions: improved
				Liver enzymes: improved.
				Leukocytosis: improved.
				Anemia: improved.
				Hypoalbumin: improved.
				Total protein: reduced.
				HbA1c: -4.9%

Secondary outcomes: Cardiometabolic risk reduction

Secondary outcomes from the literature identified four cohort studies demonstrating a significant reduction in cardiometabolic risk among patients with HS treated with GLP-1RAs. Chou et al. (2025) conducted a real-world retrospective cohort study of nearly 40,000 patients with HS over a 20-year period, revealing that GLP-1RA users exhibited consistently lower odds of cerebrovascular disease, myocardial infarction, ischemic heart disease, and heart failure compared with non-users at all follow-up intervals. ⁴² Similarly, Islam et al. (2025) analyzed data from more than 208,000 patients with HS and found that semaglutide users experienced significantly reduced rates of myocardial infarction, stroke, and cardiovascular events, with superior event-free survival across all endpoints. ⁴³ Ma et al. (2025) supported these findings in a population-based cohort of approximately 40,000 patients with HS followed for 19 years, demonstrating a reduced risk of cerebrovascular disease, ischemic heart disease, heart failure, and atherosclerosis with GLP-1RA use. ⁴⁴ In contrast, Choi et al. (2025) examined T2DM patients treated with GLP-1RAs in a multicenter database and observed that those with coexisting HS had a higher incidence of major adverse cardiovascular events compared with T2DM patients without HS. The HS subgroup was characterized by younger age, female predominance, and a higher prevalence of obesity, suggesting that HS may independently increase the risk of cardiovascular events despite GLP-1RA therapy. ⁴⁵

Clinical benefits of GLP-1RA independent of weight loss

Evidence from cohorts and case studies suggests that the clinical improvements observed with GLP-1RA therapy in HS may extend beyond weight-related effects. Gouvrion et al. (2025) reported clinical improvement in disease activity even in patients with minimal BMI change. ³⁰ Likewise, the Khandalavala (2017) case study found initial weight loss but later weight regain, although HS symptoms and inflammatory markers still improved. ³⁸ In one retrospective study, Encarnacion et al. (2025) with 67 patients with HS 64.2 % experienced improvement in disease severity with an average weight loss of 4.5 kg, whereas 35.8% showed no improvement or worsened disease activity, losing only 0.09 kg on average. ⁴⁰ Notably, no significant correlation was found between changes in BMI (p=0.77) or HbA1c (p=0.30) and clinical response in HS after GLP-1RA treatment for 4 years, suggesting that weight reduction alone does not fully explain the observed therapeutic benefits. ⁴⁰ Similarly, Nicolau et al. (2024) found no correlation between BMI changes and Hurley stage, pain in HS lesions (VAS-score) or any inflammatory parameters (Table 3).

Table 3.

Clinical Cohort studies of GLP-1RAs and Cardiometabolic Risks in HS.

Study	Population comparison	GLP-1RA regimen	Key Outcomes
Retrospective Cohort 42	GLP-1RA users and HS (n=19,920)	N/A GLP-1RA regimen 20-year duration	Cerebrovascular disease risk reduced 5.44% → 4.02%
			Acute MI reduced risk 4.38% → 3.08%
			Ischemic heart disease risk reduced 15.36% → 12.22%
			Heart failure reduced risk 11.97% → 8.75%
	Non-users and HS (n=19,920)
			Atherosclerosis reduced risk 6.15% → 4.65%
			PCI reduced risk 0.26% → 0.09%
Retrospective Cohort 45	T2DM and HS (n=9,234)	N/A GLP-1RA regimen 10-year duration	MACE Incidence increased with HS +T2DM compared with T2DM patients without HS
	T2DM and no HS (n=560,030)
Retrospective Cohort 43	GLP-1RA users and HS(n=14,850)	Semaglutide, N/A regimen	Myocardial infarction risk reduced 1.6% → 1.2%
			Incidence of stroke reduced 1.2% → 0.8%
			Event rate reduced 2.4% → 1.7%
			AMI-free survival increased 84.7% → 89.0%
	Non-users and HS (n=193,575)
			Stroke- free survival increased 69.3% → 96.3%
			Composite-MACE-free survival increased 65.1% → 81.9%
Retrospective Cohort 44	GLP-1RA users with HS (n=19,920)	N/A GLP-1RA regimen 19-year duration	Cerebrovascular disease risk reduced aOR=0.73
			Ischemic heart disease risk reduced aOR=0.77
	Non-users (n= 19,920)		Heart failure risk reduced aOR=0.71
			Atherosclerosis risk reduced aOR=0.75

Integration of GLP-1RAs into multimodal HS management

Many patients included in the reviewed studies had inadequately controlled HS despite prior treatment with topical and systemic therapies, including antibiotics, biologics, and, in some cases, bariatric surgery. Across studies, most participants continued to receive concomitant medications during GLP-1RA therapy. Evidence suggests that GLP-1RAs may be effectively integrated as an adjuvant within these existing HS therapy strategies, potentially enhancing or prolonging the therapeutic effects of biologics and reducing the need for additional systemic interventions. ¹⁴ Moreover, GLP-1RAs may positively contribute to overall healthcare utilization with reduction in visits to the emergency departments, surgical procedures, and medication costs.^13,27

While biologic therapies primarily target inflammatory cytokines, GLP-1RAs could serve as a synergistic adjuvant by addressing the underlying meta-inflammation and metabolic dysfunction characteristic of HS. Several studies have demonstrated a strong association between obesity and a diminished therapeutic response in HS, as obesity acts as both a predisposing factor and a barrier to the efficacy of medical interventions, particularly biologic therapy.^46,47

Peterson et al. (2020) analyzed 149 patients with HS from the southern USA and reported an obesity prevalence of 80.9%, significantly higher than that in the general population of 68.5%. ⁴⁶ While oral and topical antibiotics were most commonly prescribed (over 74% of treatments), biological agents, especially those targeting TNF-α, produced the most significant therapeutic response. ⁴⁶ In contrast, Nosrati et al. (2023) in a retrospective review of 57 patients treated with adalimumab (anti-TNF- α), found that patients with a BMI under 30 kg/m² exhibited significant reductions in HS-PGA and NRS pain, whereas those with a BMI over 30 kg/m² paradoxically experienced an increase in disease activity and elevations in erythrocyte sedimentation rate (ESR) and IL-6. Furthermore, inflammatory markers also increased in patients with obesity and HS treated with adalimumab. ⁴⁷

In support of a broader systemic benefit, several studies reported a reduced need for other systemic therapies with the use of GLP-1RAs. Hill et al. (2025) conducted two large retrospective cohort studies; in one, 3880 patients with HS treated with semaglutide were compared with matched controls, showing decreased use of antibiotics, biologics, steroids, and ER visits. ⁴⁸ In a second cohort, Hill et al. (2025) reported that 6639 patients with HS treated with semaglutide experienced decreased utilization of antibiotics, steroids, and ER visits, though biologic use remained unchanged. ⁴⁹ This may reflect the long-term management of biologics as opposed to other treatment interventions, which are often implemented as short-term disease management. ⁴⁹ Additionally, several case reports noted a decreased need for daily analgesics among patients treated with GLP-1RAs, further highlighting their potential to improve disease burden and quality of life.^35,36

Additionally, dietary intervention, exercise, and bariatric surgery have all been proposed and used as weight-loss strategies in HS management, based on similar mechanisms proposed for GLP-1RAs, including reduced mechanical friction, improved insulin sensitivity, and decreased systemic inflammation. ¹⁸ No studies have directly compared GLP-1RAs with dietary intervention, exercise, or bariatric surgery in patients with HS. ¹⁴ Future research and clinical practice should explore the role of GLP-1RAs as replacement for or complements to existing non-pharmacological weight-loss strategies.

Safety profile and practical considerations

Semaglutide, liraglutide, and tirzepatide are consistently described as well-tolerated, with adverse events reported as infrequent and predominantly mild across studies.^14,34 In most studies there were no treatment discontinuations due to adverse effects or any other causes, except for insurance issues.^28,29 The most common side effects were mild and gastrointestinal, such as nausea, vomiting, and diarrhea. ¹³ These side effects were also described as the most common reason for treatment discontinuation. ²⁷ Severe adverse events, such as pancreatitis, gallbladder problems, and ileus, were observed as rare and no more frequent than in control groups. ²⁷ Cutaneous reactions from GLP-1RAs include dermal hypersensitivity, typically presenting as localized itching or injection-site rashes, though generalized eruptions have occasionally been described. ²⁴ An isolated case report observed a paradoxical worsening of psoriasis on liraglutide. ¹³ Injection reactions were more frequent with long-acting formulations. ²⁴ Exenatide injected weekly showed a significantly higher occurrence of injection reactions (approximately 22%) compared with semaglutide and dulaglutide when injected weekly (1-3%). ²⁴

In regard to HS-related or bariatric surgery, GLP-1RAs may serve as an effective preoperative optimization strategy, particularly for patients with severe obesity. ¹⁸ GLP-1RAs induce a more gradual reduction in weight compared with bariatric surgery, which can help reduce complications and disease activity related to nutritional deficiencies from rapid weight loss. ²⁴ However, perioperative precautions include the risk of pulmonary aspiration from delayed gastric emptying, as well as guidelines recommending that treatment be paused before surgery. ²⁴

In some cases, GLP-1RAs have been linked to delayed wound healing. ²⁴ This complication might also be attributed to nutritional deficiencies following weight loss. ²⁴ Hair loss and changes in nail growth have also been documented, suggestively due to nutritional deficiencies. New studies further indicate a possible connection between acne and GLP-1RA use. ⁵⁰

Cosmetic complications associated with weight loss from GLP-1RAs, particularly in the face, include loss of subcutaneous fat and reduced skin elasticity. ⁵⁰ These changes can manifest as facial volume loss, dry skin, and premature aging. ⁵⁰ This emphasizes the importance of informing and counseling patients about these potential effects before initiating therapy, and consideration may be given to both surgical and non-surgical adjuvant interventions such as fillers, lipofilling, lasers, and others may be taken into consideration. ⁵⁰

Broader applications

GLP-1RAs have emerged as a valuable adjuvant therapy for patients with both IMIDs and metabolic syndrome. ²⁷ In HS, studies of GLP-1RAs have demonstrated positive outcomes, with additional benefits observed across several other dermatologic conditions, including severe PCOS (HAIR-AN syndrome), Hailey-Hailey disease, acne keloidalis nuchae, folliculitis decalvans, androgenetic alopecia, and congenital linear scleroderma. ¹³ Beyond dermatology, GLP-1RAs have shown therapeutic potential in gastrointestinal, immune-mediated, rheumatological, cardiovascular, hepatic, and neurologic disorders.^18,27 Clinical improvements are frequently accompanied by enhanced metabolic profiles, including reductions in BMI, HbA1c, cholesterol, improvements in insulin sensitivity, and reductions in inflammatory markers such as CRP and IL-6.^14,27 Preclinical and clinical evidence further indicates that GLP-1RAs may reduce the use of alcohol, nicotine, and opioids by modulating neural reward systems. ¹⁸

Limits and future research

Recent reviews have summarized the early clinical evidence on GLP-1RAs in HS. This narrative review adds value by integrating HS-specific clinical outcomes with cardiometabolic effects, proposed mechanisms, safety considerations, and practical use within multimodal HS care. However, several limitations should be acknowledged. Despite encouraging early evidence, the available clinical data consist of small cohorts and single case reports. Larger randomized, placebo-controlled trials are needed to clarify the long-term efficacy and safety of GLP-1RAs in HS.^14,27 The quality assessment indicated that the included cohorts and case reports were generally of moderate methodological quality. Cardiovascular outcome cohorts scored slightly higher, as they included comparator groups and larger sample sizes. (Supplementary Table 2).

Additionally, reported outcomes were substantially heterogeneous across studies and relied mainly on Hurley staging, HS-PGA, lesion counts, and patient-reported outcomes rather than on IHS4, which is considered one of the best instruments for assessing HS disease activity in clinical research. ⁵¹ This limits objective comparison of lesion burden before and after GLP-1RA use. Similar limitations were emphasized by Birda et al. and Tassavor et al., who highlighted heterogeneous follow-up intervals, treatment regimens, and outcome reporting as major barriers to statistical synthesis and meta-analysis.^13,27

Furthermore, the clinical evidence for the direct anti-inflammatory effects of GLP-1RAs proposed in this review remains weak and limited by the absence of statistical validation from larger clinical samples. To better define therapeutic potential, further studies are needed to explore the anti-inflammatory effects of GLP-1RAs that occur independently of weight loss and glycemic control.^13,23 The proposed anti-inflammatory mechanisms of GLP-1RAs must also be interpreted cautiously, as current evidence primarily stems from non-HS experimental models. Future research should also include head-to-head comparisons between GLP-1RAs to determine which agents have more beneficial dermatological effects. Notably, most existing data are based on populations with obesity, while effects in patients without obesity remain undefined. ¹³

Conclusion and clinical implications

Emerging evidence suggests that the effects of GLP-1RAs in HS are pleiotropic. While weight loss reduces metabolic dysfunction and mechanical friction in intertriginous areas, direct anti-inflammatory mechanisms may play a central role in disrupting the chronic inflammatory cascade driving HS pathogenesis and its associated comorbidities. Collectively, the literature indicates that GLP-1RAs could represent a valuable adjunct to multimodal therapy for HS, enhancing the efficacy of existing therapeutic regimens and potentially reducing the need for additional interventions.

Treatment with GLP-1RAs may be particularly beneficial for patients with refractory HS and concurrent metabolic comorbidities, for whom reducing systemic inflammation represents a key strategy in managing this group of patients with a high disease burden.

Appendix.

Abbreviations

AMPK

AMP-activated protein kinase

BDI

Beck Depression Inventory

BMI

Body Mass Index

CCK

Cholecystokinin

CRP

C-reactive protein

DLQI

Dermatology Life Quality Index

EGF

Epidermal Growth Factor

ESR

Erythrocyte Sedimentation Rate

FGF

Fibroblast Growth Factor

GCG-RA

Glucagon Receptor Agonist

GIP

Glucose-dependent Insulinotropic Polypeptide

GIP-RA

Gastric Inhibitory Polypeptide Receptor Agonist

GLP-1

Glucagon-Like Peptide-1

GLP-1RA

Glucagon-Like Peptide-1 Receptor Agonist

HbA1c

Hemoglobin A1c

HiSCR

Hidradenitis Suppurativa Clinical Response

HS

Hidradenitis Suppurativa

HS-PGA

Hidradenitis Suppurativa Physician Global Assessment

Hurley SI-III

Hurley Staging System I-III

IDEOM

International Dermatology Outcome Measures

IL

Interleukin

IMID

Immune-Mediated Inflammatory Disease

IBD

Inflammatory Bowel Disease

iNKT-cells

Invariant Natural Killer T Cells

LDL

Low-Density Lipoprotein

M2

Alternatively Activated Macrophage

MACE

Major Adverse Cardiovascular Event

MMP

Matrix Metalloproteinase

MS

Multiple Sclerosis

MSK-Q

Musculoskeletal Questionnaire

NF-κB

Nuclear Factor kappa-light-chain-enhancer of activated B cells

NLR

Neutrophil-to-Lymphocyte Ratio

NO

Nitric Oxide

NRS

Numeric Rating Scale

PAMP

Pathogen-Associated Molecular Pattern

PCOS

Polycystic Ovary Syndrome

PI3K

Phosphatidylinositol 3-Kinase

PYY

Peptide YY

ROS

Reactive Oxygen Species

SII

Systemic Immune-Inflammatory Index

SIRI

Systemic Inflammation Response Index

SOD

Superoxide Dismutase

Th

T-helper Cell

TNF-α

Tumor Necrosis Factor Alpha

T2DM

Type 2 Diabetes Mellitus

VEGF

Vascular Endothelial Growth Factor

VAS

Visual Analogue Scale

VSMC

Vascular Smooth Muscle Cell.

ORCID iDs

Emma Brogaard https://orcid.org/0009-0007-3752-4114

Simon Francis Thomsen https://orcid.org/0000-0002-4838-300X

Ethical considerations

There are no human participants in this article and informed consent is not required.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.*