The effects of GLP‐1RA on inflammatory skin diseases: A comprehensive review

Abstract

Glucagon‐like peptide 1 receptor agonists (GLP‐1RA) are commonly used as treatment for type 2 diabetes mellitus and obesity. GLP‐1RA have been found to be valuable therapeutic approaches not only for glucose control, but also for weight loss and cardiovascular risk reduction. It has also been established that GLP‐1RA have immunological and anti‐inflammatory effects. The aim of this article was to comprehensively review the literature and to collect, analyse and quantitatively resynthesize evidence on the possible effects of GLP‐1RA on inflammatory skin diseases. Through body weight reduction and subsequent systemic inflammation reduction, but mainly through their direct interaction with signalling pathways of inflammation and immune cells, GLP‐1RA can improve psoriasis and hidradenitis suppurativa (HS). Clinical data of the positive effects of GLP‐1RA in patients with psoriasis and HS are presented. Moreover, the immune cells and inflammatory pathways affected by GLP‐1RA are discussed.

The graphical abstract illustrates the aim of this article, which was to comprehensively review the literature and to collect, analyse and quantitatively resynthesize evidence on the possible effects of GLP‐1RA on inflammatory skin diseases. The actions of GLP‐1RA on glucose regulation, weight management and cardiovascular risk are listed, while the immunoregulative effects are presented.

Why was the study undertaken?

The aim of this article was to comprehensively review the literature on the possible role of GLP‐1RA in inflammatory skin diseases. With the expanded use of GLP‐1RA, this topic is important for all dermatologists.

What does this study add?

In this review article, the effects of the GLP‐1RA on specific skin diseases, namely psoriasis and hidradenitis suppurativa, are presented.

What are the implications of this study for disease understanding and/or clinical care?

GLP‐1RA are valuable therapeutic approaches for T2DM, weight loss and cardiovascular risk reduction. However, GLP‐1RA are also immunoregulative medications, which may affect inflammatory skin conditions and thus bear significance for the practice of dermatology.

INTRODUCTION

Glucagon‐like peptide 1 receptor agonists (GLP‐1RA) are a class of recent but commonly used medications for patients suffering from type 2 diabetes mellitus (T2DM) and obesity. T2DM is closely related to obesity and insulin resistance, which leads to poor glucose control. ¹ Patients with T2DM face multiple complications, but the possible consequences in skin health have yet to be well documented.

GLP‐1 is an incretin hormone produced by enterocrine L cells localized in the duodenum. L‐cells are stimulated by nutrients after meals, leading to a rapid increase in the plasma levels of the GLP‐1. ² The hormone increases the secretion of insulin after a meal and reduces the secretion of glucagon. ² Consequently, GLP‐1RAs are a good therapeutic choice for glycaemic control in patients with T2DM without increasing the risk for hypoglycaemia. ² GLP‐1 also delays gastric emptying, slowing down the absorption of glucose and reducing appetite. The above effects explain why GLP‐1RAs can be used as a treatment for obesity. ² , ³ Besides glucose regulation and weight reduction, treatment with GLP‐1RAs has been shown to decrease the risk of cardiovascular complications and cardiovascular mortality (Figure 1). ⁴ , ⁵ , ⁶ Recent data have also shown that GLP‐1RAs have immunoregulating effects and can reduce systemic inflammation and systemic aging. ⁴ , ⁵ , ⁷ Both GLP‐1 and GLP‐1RAs bind with a transmembrane GLP‐1 receptor, coupled with a G‐protein which activates the adenylic cyclase and increases cAMP levels. GLP‐1Rs are located in many tissues, one of which is the skin. This implies that GLP‐1RA therapy may have several effects in the skin. ⁸

FIGURE 1.

Actions of GLP‐1RA on glucose metabolism. The direct and indirect metabolic effects of the GLP‐RA on various organs are presented.

Since 2014, FDA has approved daily subcutaneous injections with liraglutide as a treatment for T2DM (1.8 mg) and obesity (3 mg). ⁹ Furthermore, semaglutide was also approved by FDA in 2017 for T2DM (1 mg) and obesity (2.4 mg), and it is administered via subcutaneous injections once a week. ¹⁰ Dulaglutide has been approved in the form of weekly subcutaneous injections for T2DM (1.5 mg), ⁹ as well as exenatide and lixisenatide. ¹¹ , ¹² FDA has also approved a dual‐acting GLP‐1 and GIP receptor agonist for T2DM and obesity, tirzepatide. ¹³ Finally, there are several drugs in development for T2DM and obesity. ¹⁴ Retatrutide is a triple‐acting GLP‐1, GIP and glucagon receptor (GCG) agonist, is in a phase 3 clinical trial. ¹⁵ Mazdutide and sulvodutide are dual GLP‐RA and GCG‐RA, and orforglipron and encoglutide are GLP‐1RA in phase 3 clinical trials. ¹⁴ , ¹⁶ , ¹⁷

Recent studies are providing evidence towards a positive outcome for patients with psoriasis and hidradenitis suppurativa who receive GLP‐1RA for T2DM. ¹⁸ , ¹⁹ , ²⁰ , ²¹ The improvement in patient outcomes is possibly a result of the immunological effects of GLP‐1RA. ²¹ , ²² , ²³ , ²⁴ Further research is required to show the exact mechanisms by which GLP‐1RA affects skin physiology and disease. The aim of this article was to comprehensively review the literature and to collect, analyse and quantitatively resynthesize data on the possible effects of the GLP‐1RA on inflammatory skin diseases, such as psoriasis and hidradenitis suppurativa (Table 1)

TABLE 1.

List of GLP‐1RA medications with FDA approval or in development.

Generic name	Receptor agonist	Trade name	FDA approval	Indication
Liraglutide	GLP‐1RA	Victoza	FDA approved (2010)	T2DM
Liraglutide	GLP‐1RA	Saxenda	FDA approved (2014)	Obesity
Semaglutide	GLP‐1RA	Ozempic	FDA approved (2017)	T2DM
Semaglutide	GLP‐1RA	Wegovy	FDA approved (2021)	Obesity
Semaglutide	GLP‐1RA	Rybelsus	FDA approved (2019)	T2DM
Exenatide	GLP‐1RA	Byetta	FDA approved (2005)	T2DM
Exenatide	GLP‐1RA	Bydureon BCise	FDA approved (2017)	T2DM
Dulaglutide	GLP‐1RA	Trylicity	FDA approved (2014)	T2DM
Lixisenatide	GLP‐1RA	Adlyxin	FDA approved (2016)	T2DM
Tirzepatide	Dual GLP‐1RA + GIP‐RA	Mounjaro	FDA approved (2022)	T2DM
Tirzepatide	Dual GLP‐1RA + GIP‐RA	Zepbound	FDA approved (2023)	Obesity
Retatrutide	Triple GLP‐1RA + GIP‐RA + GCG‐RA		Ongoing phase 3 clinical trial
Orforglipron	Oral GLP‐1RA		Ongoing phase 3 clinical trial
Ecnoglutide	GLP‐1RA		Ongoing phase 3 clinical trial
Mazdutide	Dual GLP‐1RA and GCG‐RA		Ongoing phase 3 clinical trial
Survodutide	Dual GLP‐1RA and GCG‐RA		Ongoing phase 3 clinical trial

Note: This table lists drugs either with FDA approval or in development (Ongoing phase 3 clinical trial).

Abbreviations: GLP‐1RA, glucagon‐like peptide 1 receptor agonist; GIP‐RA, gastric inhibitory polypeptide receptor agonist, GCG‐RA, glucagon receptor agonist; T2DM, type 2 diabetes mellitus.

PSORIASIS

The pathogenesis of psoriasis involves the stimulation of immune cells such as T helper cells 17 (Th17) and γδ T cells. This leads to increased production of proinflammatory cytokines, including TNF, IL‐12, IL‐17 and IL‐23, which activate keratinocytes and create an inflammatory environment. ²⁵

Patients with psoriasis have a high risk for developing diabetes because of common pathogenic mechanisms between the two diseases. ²⁶ There is some evidence which indicates that diabetes and chronic hyperglycaemia can increase inflammation and therefore worsen psoriasis. ²⁰ It has been hypothesized that GLP‐1RA can reduce inflammatory mediators caused by glucose toxicity. However, no other glucose regulating treatment has been proven to improve psoriasis, while research supports that the positive effects of GLP‐1RA treatment are not related to lower blood glucose. ²⁰ GLP‐1RA are also used for the treatment of obesity. Obesity is characterized by low‐grade chronic inflammation and poses as an independent risk for inflammatory skin conditions such as psoriasis. ²⁷ Weight loss can improve the severity of psoriasis because of the reduction of the inflammatory mediators. ²⁰ Several studies have shown the remission of psoriasis in obese patients who have undergone bariatric surgery. Roux‐en‐Y gastric bypass (RYGB) changes the anatomy as well as the physiological mechanisms of the gastrointestinal tract. The nutrients end up in a distal part of the jejunum and stimulate the production and secretion of GLP‐1 produced by the L cells. That results in increased levels of GLP‐1, while a significant improvement of Psoriasis Area and Severity Index (PASI) in patients with psoriasis has been observed immediately after the procedure. ²⁸ , ²⁹ It has also been shown that GLP‐1 and analogues have anti‐inflammatory effects as well. ⁵ , ⁷ , ²¹ , ²² Consequently, GLP‐1RA may improve psoriasis in patients through various mechanisms (Figures 2 and 3).

FIGURE 2.

The effect of GLP‐1RA on iNKT cells. INKT cells upon stimulation are able to produce inflammatory cytokines, which are involved in the pathogenesis of psoriasis. The activation of the iNKT cells is possible when a lipid antigen is being presented by CD1d to the iNKT cell. The iNKT cell express GLP‐1R. Stimulation of the receptor inhibits NF‐kB, and thus, the secretion of proinflammatory cytokines.

FIGURE 3.

Suggested mechanisms responsible for improvement in psoriasis severity in patients receiving GLP1‐RA. GLP‐1RA: glucagon‐like peptide 1 receptor agonist, iNKT cells: invariant natural killer T cells, NF‐kB: nuclear factor kappa B, TNF‐a: tumour necrosis factor‐a, PI3K: phosphatidylinositol‐4,5‐bisphosphate 3‐kinase, SDF‐1: stromal cell‐derived factor 1.

The therapeutic effect for patients with psoriasis who receive GLP‐1RA for T2DM has been established and reported by several researchers. Their studies suggest that patients treated with GLP‐1RA showed a significant improvement in psoriasis before their glycaemic regulation or reduction of their body weight. ²² , ³⁰ , ³¹ , ³² , ³³ More specifically, Hogan et al. ²² observed an improvement in psoriasis in three obese patients with T2DM, who received treatment with GLP‐1RA. The index patient showed an improvement within 48 h of treatment initiation, and the two other patients had a significant reduction in PASI after 6 weeks of treatment. In addition, there was an increased number of invariant natural killer T (iNKT) cells in the blood circulation, as well as a decreased number in psoriasis plaques following 6 weeks of treatment.

The therapeutic effect of the GLP‐1RA has also been reported in a randomized controlled trial by Lin et al., ³³ where patients from the treatment group showed an improvement in psoriasis severity and decreased body weight. In this study, although patients from both groups had reduced expression of IL‐23, IL‐17 and TNF‐a, patients that received GLP‐1RA had significantly reduced levels of IL‐23 and IL‐17, indicating the anti‐inflammatory effects of the GLP‐1RA.

In a study conducted by Faurschou et al., ³⁴ liraglutide was studied in obese patients with psoriasis who did not suffer from T2DM. Patients were randomized into two groups and received either liraglutide or placebo. The study confirmed the effects of liraglutide in weight loss and cholesterol levels but found no significant difference in PASI between the two groups (Table 2).

TABLE 2.

Studies investigating the association between GLP‐1RA treatment for T2DM and PASI, BMI, DLQI and iNKT cells.

Study	Patients	GLP‐1RA	PASI		BMI (kg/m2)		HbA1c (%)		DLQI		INKT cells (% of lymphocytes)
			Before	After	Before	After	Before	After	Before	After	Before		After
Glucagon‐like peptide‐1 (GLP‐1) and the regulation of human invariant natural killer T cells: Lessons from obesity, diabetes and psoriasis, Hogan et al. 22	Index patient, 60‐year‐old female	Exenatide (2 weeks)	>15	10.5
	Participant 1, 48‐year‐old male	Liraglutide (6 weeks)	13.2	10.8	48.0	46.5	5.7	5.6			Skin	Blood	Skin	Blood
											2.16	0.15	0.07	0.60
	Participant 2, 49‐year‐old male	Liraglutide (6 weeks	4.8	3.8	43.0	41.1	5.9	5.8			0.32	0.16	0.00	0.57
Two birds one stone: Semaglutide is highly effective against severe psoriasis in a type 2 diabetic patient, Costanzo et al. 19	73‐year‐old male	Semaglutide (1 mg/week for 10 months)	33.2	2.6	42.7	38.3	7.9	5.4	26	0
Improvement of psoriasis during glucagon‐like peptide‐1 analogue therapy in type 2 diabetes is associated with decreasing dermal γδ T‐cell number: A prospective case‐series study, Buysschaert et al. 39	7 patients	Liraglutide (6 patients) Exenatide (1 patient) For 18 ± 2 weeks	12.0 ± 5.9	9.2 ± 6.4	32 ± 10.1	30.6 ± 9.1	7.5 ± 1.2	6.5 ± 0.8
Treatment with liraglutide, a glucagon‐like peptide‐1 analogue, improves effectively the skin lesions of psoriasis patients with type 2 diabetes: A prospective cohort study, Xu et al. 20	7 patients	Liraglutide (1.8 mg for 12 weeks)	15.7 ± 11.0	2.2 ± 3.0	23 ± 4	21 ± 3	8.1 ± 2.3	6.4 ± 0.8	21.8 ± 7	4.1 ± 3.9
Glucagon‐like peptide‐1 receptor agonist liraglutide therapy for psoriasis patients with type 2 diabetes: a randomized‐controlled trial, Lin et al. 33	11 patients	Liraglutide (1.8 mg/week)	14.2 ± 10.67	2.4 ± 2.71		−1.77 ± 0.73		−1.77 ± 0.73		−18.18 ± 5.86
Improvement in psoriasis after treatment with the glucagon‐like peptide‐1 receptor agonist liraglutide, Faurschou et al. 40	59‐year‐old male	Liraglutide (1.8 mg for 12 weeks)	PGA		29.3	26.8	8.9	5.9
			3	1
Glucagon‐like peptide‐1 analogue therapy for psoriasis patients with obesity and type 2 diabetes: A prospective cohort study, Ahern et al. 32	7 patients	Liraglutide (1.2 mg/day for 10 weeks)	PASI		Body weight (kg)		Fasting glucose plasma levels (mmol/L)		6	2
			4.8	3.0	137.8	130.1	6.1	5.8

Note: This table presents in the first three columns the name of the study, the patients with T2DM and psoriasis who participated and the GLP‐1RA therapy they were treated with. The other columns present the change in PASI, PGA, BMI, body weight, HbA1c, fasting glucose plasma levels, DLQI and iNKT cell levels in skin and circulation after the treatment.

Abbreviations: BMI, body mass index; DLQI, dermatology life quality index; GLP‐1RA, glucagon‐like peptide 1 receptor agonist; HbA1c, haemoglobin A1c; iNKT cells, invariant natural killer T‐cells; PASI, psoriasis area and severity index; PGA, physician global assessment; T2DM, type 2 diabetes mellitus.

POSSIBLE IMMUNOLOGICAL EFFECTS

iNKT cells are a category of natural killer T cells (NKT cells). NKT cells are T lymphocytes that express both NK cell surface markers and T cell receptors (TCR), and are able to recognize lipid antigens when presented by CD1d, a non‐classical MHC molecule. TCR, lipid antigen and CD1d interaction results in a rapid production of cytokines, chemokines and transcription factors. More specifically, iNKT cells, after being presented with a‐Gal‐Cer lipid antigen, secrete IFN‐γ, IL‐4 and other cytokines as well as inflammatory molecules (IL‐2, IL‐10, IL‐17, TNF‐a, GM‐CSF). ³⁵ iNKT cells play an important role in the pathogenesis of psoriasis and other inflammatory diseases. A study by Hogan et al. ²² has reported that in patients with psoriasis, circulating iNKT cell levels are lower than in healthy individuals, while psoriatic plaques are infiltrated by iNKT cells. In the same study, it has been shown that GLP‐1 RA can affect iNKT cells by redistributing iNKT cells from skin to blood circulation. An explanation for why iNKT cell levels are higher in psoriasis plaques could be attributed to the increased expression of CD1d in psoriatic keratinocytes.

A study by Faurschou et al. ³⁰ on the expression of GLP‐1R in psoriatic plaques reported that the receptor was expressed in skin biopsies of patients with psoriasis, but not in unaffected skin or healthy individuals. Further analysis showed no expression of the GLP‐1R in keratinocytes. However, gene analysis found that GLP‐1R was expressed in blood samples from patients with psoriasis. This leads to the conclusion that GLP‐1R detected on the skin of patients with psoriasis is mainly expressed on immune cells, such as iNKT cells, that infiltrate the plaques.

Studies have shown that iNKT cells express GLP‐1R, coupled with a G‐protein. ²² The stimulation of the receptor and the G‐protein activates the adenylic cyclase and increases cAMP levels. This results in the activation of protein kinase A (PKA) and eventually leads to the phosphorylation of the transcription factor CREB, which, upon activation, inhibits the stimulating pathway of NF‐kB and thus the transcription of proinflammatory mediators. ³⁶ Although GLP‐1RA can activate the receptor, as shown by the upregulation of cAMP production, the secretion of proinflammatory mediators is inhibited. This further indicates that GLP‐1RA can improve psoriasis by targeting iNKT cells. Phosphorylation and activation of the transcription factor CREB is also known to induce the production of the anti‐inflammatory cytokine IL‐10. Although the correlation between GLP‐1RA and IL‐10 is not clarified, it indicates a therapeutic effect on patients with T2DM/obesity and psoriasis. ²²

Another line of evidence comes from the effects of GLP1‐RA on dermal γδ T cells, which are a subtype of CD3+ T cells located in the dermis. Dermal γδ T cells, upon stimulation from IL‐23, can produce the vast majority of IL‐17 which is secreted by dermal T cells. ³⁷ , ³⁸ In psoriasis, the increased production of IL‐23, due to the activation of the DCs and macrophages, leads to the increased secretion of IL‐17 by γδ T cells. It has also been reported that in psoriatic plaques, the proportion of γδ T cells is increased. ³⁸ Considering that, γδ T cells are involved in the pathogenesis of psoriasis and may be a therapeutic target.

A study by Buysschaert et al. ³⁹ showed the improvement of psoriasis in patients receiving exenatide or liraglutide, which was associated with the effect of the GLP‐1RA on dermal γδ T cells. Biopsies from patients before treatment measured an increased percentage of dermal γδ T cells in psoriasis plaques compared to unaffected skin (5.9 ± 4.6% vs. 4.2 ± 3.6%), as well as an increased expression of IL‐17. At the end of 20 weeks, five out of seven patients had improved lesions, a reduction in their PASI and there had also been observed a significant reduction of dermal γδ T cells (from 5.9 ± 4.6% to 2.9 ± 3.5%) indicating a correlation between GLP‐1RA and γδ T cells.

The effects of the GLP‐1RA in psoriasis are mostly dependent on their interaction with immune cells. Besides the effects on iNKT cells and γδ T cells, GLP‐1RA regulates lymphocyte migration, macrophage activation and cytokine production. There is some evidence that GLP‐1RA inhibits the signalling of TNF‐a. TNF‐a stimulates NF‐kB and increases inflammation by expressing proinflammatory cytokines. GLP‐1RA can interfere with the signalling pathway of TNF‐a by inhibiting NF‐kB, and thus, the production of proinflammatory mediators. ³¹ , ⁴⁰ GLP‐1RA also interferes with stromal cell‐derived factor 1(SDF‐1), a chemokine normally responsible for lymphocyte recruitment. GLP‐1RA decreases SDF‐1, and as a result, reduces the migration of the CD4+ lymphocytes. ²⁴ , ⁴¹ A final interaction between GLP‐1 and skin immunity is through the phosphatidylinositol‐4,5‐bisphosphate 3‐kinase pathway, which normally activates signalling cascades responsible for proliferation and cell growth. Studies have indicated that GLP‐1RA can inhibit the phosphatidylinositol‐4,5‐bisphosphate 3‐kinase pathway, and in that way reduce the migration and proliferation of the immune cells. ²³ , ²⁴ , ⁴¹

HIDRADENITIS SUPPURATIVA

Hidradenitis suppurativa (HS) is characterized by the stimulation of the immune cells and the production of proinflammatory cytokines such as TNF‐a, IL‐1a, IL‐1b, IL‐12, IL‐17 and IL‐23. ⁴² One of the most common comorbidities in patients with HS is obesity. Obese patients have larger skin folds, causing increased mechanical friction and creating a humid environment. Obesity is also characterized by a low‐grade inflammatory state which aggravates HS. ⁴²

Research shows that the GLP‐1RA are a promising therapy for patients with HS. GLP‐1RA have been used as a treatment for obesity. Obesity is a key factor for the HS, and the reduction of body weight can improve the quality of life of patients by decreasing the mechanical friction on skin folds. GLP‐1RA can lower body weight in a safe way, as some evidence indicates that rapid weight loss and excess skin can worsen HS. ⁴³ Reduction of body weight also reduces low‐grade inflammatory state that accompanies obesity and adipokines produced by adipose tissue. ⁴³

The immunoregulative effects of the GLP‐1RA can also improve HS. As shown in psoriasis, GLP‐1RA can inhibit TNF‐a through NF‐kB, resulting in the decreased production of cytokines. ⁷ , ²³ , ⁴⁰ The suppression of proinflammatory cytokines induced by TNF‐a, such as IL‐17 and IL‐23, which are involved in the pathogenesis of HS, leads to a reduction of the inflammatory state and remission of the disease. ⁴⁴ , ⁴⁵ , ⁴⁶ Furthermore, GLP‐1RA has been shown to reduce the secretion of monocyte chemotactic protein 1 and, therefore, decreases the migration and activation of monocytes. ⁴⁴ , ⁴⁷

Studies about the effects of the GLP‐1RA in patients with HS are limited. A study by Nicolau et al. ⁴³ stressed a significant improvement in HS severity in 14 obese patients with HS receiving liraglutide. After the treatment with liraglutide, patients average Hurley scores and DLQI were reduced, and there was also a significant reduction in ultrasensitive C‐reactive protein and other systemic inflammatory markers. The improvement of HS was a result of weight loss. Similar findings have been observed in another study conducted by Lyons. ⁴⁸ However, the benefit that therapy with GLP‐1RA has over other obesity treatments is the effect on the immune cells. GLP‐1RA can reduce the production of proinflammatory cytokines such as IL‐17, by inhibiting stimulating pathways of TNF‐a and NF‐kB. ⁷ , ²³ , ⁴⁰ There are limited studies investigating the anti‐inflammatory effects of the most recent anti‐diabetic dual‐acting GLP‐1RA/GIP‐RA agent, tirzepatide. ⁴⁹ , ⁵⁰ However, tirzepatide has been found beneficial for HS in one case study by Chan et al (Table 3). ⁵¹

TABLE 3.

Studies investigating the association between GLP‐1RA treatment and DLQI, PGA, Hurley Stage, BMI and HbA1c in patients with HS.

Study	Patients	GLP‐1RA	DLQI		VAS		PGA		Hurley stage		BMI (kg/m2)		HbA1c (%)
			Before	After	Before	After	Before	After	Before	After	Before	After	Before	After
Liraglutide for the treatment of obesity among patients with hidradenitis suppurativa. Nicolau J., et al. 43	14 patients with obesity	Liraglutide (3 mg/week for 3 months)	12.3 ± 2.8	9.7 ± 6.9	5.6 ± 1.5	3.2 ± 1.6			2.6 ± 0.5	1.1 ± 0.3	39.3 ± 6.2	35.6 ± 5.8	5.7 ± 0.5	5.4 ± 0.4
Semaglutide for weight loss in people with obesity as an adjunctive treatment for hidradenitis suppurativa: its impact on disease control and quality of life. Lyons D., et al. 48	30 patients with obesity	Semaglutide (0.8 mg/week for 8.2 weeks)	13	9							43.1	41.5	5.7	5.5
The treatment of hidradenitis suppurativa with the glucagon‐like peptide‐1 agonist liraglutide. Jennings L., et al. 46	31‐year‐old female with obesity	Liraglutide (1.8 mg/week for 8 weeks)	24	14			4	1			45.3	Weight loss of −6.5 kg
A case of recalcitrant hidradenitis suppurativa concomitantly treated with tirzepatide. Chan L., et al. 51	20‐year‐old female with T2DM, obesity, PCOS	Tirzepatide (7.5 mg/week for 3 months)	14	3	3	1	3	2			41.36	33.63	10.1	5.4

Note: This table presents in the first three columns the name of the study, the patients with HS and other comorbidities which may have who participated and the GLP‐1RA therapy they were treated with. The other columns present the change in DLQI, VAS, PGA, Hurley state, BMI and HbA1c after the treatment.

Abbreviations: BMI, body mass index; DLQI, dermatology life quality index; GLP‐1RA, glucagon‐like peptide 1 receptor agonist; HbA1c, haemoglobin A1c; PGA, physician global assessment; T2DM, type 2 diabetes mellitus; HS, hidradenitis suppurativa; VAS, visual analog scale.

CONCLUSIONS

While obesity and T2DM are global epidemics, GLP‐1RA have been found to be valuable therapeutic approaches not only for glucose control, but also for weight loss and cardiovascular risk reduction. GLP‐1RA present repercussions on the skin too. The positive effects of GLP‐1RA on psoriatic lesions in patients with psoriasis and T2DM have been well documented. Through body weight reduction and subsequent systemic inflammation reduction, but mainly through their direct interaction with signalling pathways of inflammation and immune cells, GLP‐1RA can improve psoriasis. GLP‐1RA act on immune cells, such as iNKT cells, γδ T cells, lymphocytes and macrophages. In this way, they reduce the production of pro‐inflammatory cytokines and prevent the migration and proliferation of immune cells in patients with psoriasis. GLP‐1RA therapy in patients with HS, similarly to psoriasis, reduces inflammation by inhibiting TNF‐a, NF‐kB, the production of pro‐inflammatory cytokines and the migration of macrophages. Further research needs to be conducted to shed more light on pathways through which GLP‐1RA affect immune cells and consequently other inflammatory skin conditions. Finally, further research is required to evaluate whether the most recent dual‐acting GLP‐1RA/GIP‐RA, tirzepatide and GLP‐1RA currently in investigation can also be beneficial for inflammatory skin diseases.

AUTHOR CONTRIBUTIONS

IAP, SAP and AJS conceived the idea of the paper and designed the structure of the article. IAP and ES searched the literature. IAP and ES wrote the first draft. SAP, TP, EN and AJS revised the manuscript. All authors approved the final version of the article.

FUNDING INFORMATION

None.

CONFLICT OF INTEREST STATEMENT

SAP has received honoraria for lectures or support for scientific meetings from Novo Nordisk and Lilly. Other authors have no relevant conflict of interest.

ETHICAL APPROVAL

Not applicable.

ETHICS STATEMENT

Not applicable.

Paschou IA, Sali E, Paschou SA, Psaltopoulou T, Nicolaidou E, Stratigos AJ. The effects of GLP‐1RA on inflammatory skin diseases: A comprehensive review. J Eur Acad Dermatol Venereol. 2025;39:2047–2055. 10.1111/jdv.20694

DATA AVAILABILITY STATEMENT

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