Pipeline and Potential Roles for GLP-1RAs in Dermatology

Having reviewed the mechanism of action and current roles in medicine for glucagon-like peptide 1 receptor agonists (GLP-1RAs), we now can discuss therapies in this class currently under investigation for management of dermatologic disease.

There is only one oral GLP-1RA (semaglutide) with an FDA-approved indication for the management of type 2 diabetes mellitus (T2DM) at this time.¹ Oral semaglutide is a peptide-based medication, which requires administration on an empty stomach, at least 30 minutes prior to the first meal, beverage or other oral medications of the day for full absorption.² Attempts have been made to develop non-peptide, small-molecule GLP-1RAs without this fasting requirement.³ Danuglipron was one such therapy showing initially promising clinical trial data; however, it has since been withdrawn by the sponsor due to potential drug-induced liver injury.^4,5 Many other non-peptide, small-molecule GLP-1RAs are currently under investigation, including orforglipron, aleniglipron, BLX7006, HDM1002, and CT-996, among others.⁶ Eli Lilly recently released results from its phase 3 ATTAIN-2 trial for the effects of orforglipron in patients with overweight/obesity and T2DM; results showed significant weight loss and meaningful hemoglobin A1c (HbA1c) reduction observed.⁷

Novel medications with additional signaling pathway action to GLP-1RAs are under investigation currently. Tirzepatide is a dual GLP-1RA and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist that is currently FDA-approved for management of both weight loss and T2DM.⁸⁹ Similar to GLP-1, GIP increases insulin secretion; however, the rationale for combining with GLP-1RAs (rather than creating a therapy with GIP receptor agonism alone) comes from studies demonstrating that GIP administration did not impact appetite like GLP-1RA.¹⁰ Other forms of dual-agonism are being investigated, such as the addition of glucagon receptor agonists (GCGR). The use of GCGR in patients with overweight and T2DM was met with initial controversy due to glucagon’s role in hepatic/skeletal muscle glycogenolysis and its counter-regulator action on insulin. However, glucagon’s promotion of lipid metabolism can lead to weight reduction when used in combination with GLP-1RA, and this combination has demonstrated efficacy in both weight loss and the lowering of blood glucose levels.^10,11 Dual-agonists of GLP-1R/GCGR under investigation include survodutide, pemvidutide, and mazdutide.^6,10 The novel triple agonists (GLP-1R/GIP/GCGR) retatrutide and efocipegtrutide also are currently being investigated.^6,10

GLP-1RAs have potential roles for indications beyond weight loss and T2DM, as discussed previously. Inflammatory dermatologic disorders are of particular interest, including psoriasis, hidradenitis suppurativa (HS) and Hailey-Hailey disease.^12,13 GLP-1RAs have demonstrated anti-inflammatory effects through reduction of pro-inflammatory cytokines via inhibition of tumor necrosis factor alpha (TNF-α) and nuclear factor-kappa B; enhancement of anti-inflammatory effects via GLP-1 receptors on T-cells; and inhibition of IL-23, IL-17, and IL-22. Several case reports and prospective cohort studies have reported improvement in patients with psoriasis placed on GLP-1RAs for T2DM and/or obesity.¹² Lin et al performed a small, randomized controlled trial of 25 patients to test liraglutide’s effect on psoriasis in patients with concomitant T2DM. After 12 weeks, 12 patients (48%) given liraglutide demonstrated significant improvement in dermatology life quality index (DLQI) and baseline value of psoriasis area and severity index (PASI) compared to the 13 control group patients.¹⁴ Similar findings have been reported with semaglutide in patients with psoriasis.¹⁵ Another systematic review reports on the use of liraglutide and semaglutide as adjunctive therapy in HS via reduction in weight and systemic inflammation, although none of the studies included in the analysis were comparative or randomized controlled trials.¹⁶

The reduction of adipose tissue with the use of GLP-1RAs could potentially serve as an additional, indirect mechanism to improve inflammatory dermatologic disorders. Adipose tissue’s chronic, low-grade inflammatory effect is exacerbated in individuals with obesity.¹⁷ In post-bariatric surgery, improvements in psoriasis have been noted, directly related to the degree of postoperative weight loss.¹⁸ Obesity has been reported to lessen biologic therapy effectiveness on inflammatory disorders, particularly those that do not utilize weight-based dosing.^19-21 TOGETHER AMPLIFY-PsO is a phase 4, open-label clinical trial recruiting to investigate tirzepatide’s effectiveness in patients with psoriasis on ixekizumab, an IL-17 inhibitor.6 Many weight-based biologics require infusion therapy, which can have practical barriers for patients, such as access to an infusion center, infusion reactions, and the time commitment necessary for infusion administration. Further investigation is needed to determine if adjunct therapy with GLP-1RAs will make a meaningful difference in inflammatory skin disorders, particularly in patients treated with weight-based biologics that only saw partial response to approved dosages. 

Many dermatologic disorders carry metabolic and cardiovascular co-morbidities, including obesity and T2DM.¹² Adjunctive GLP-1RA therapy has a clearly established role in improving obesity and T2DM, with further trials underway for their role in a host of comorbidities. Separate from their potential direct benefit in dermatologic disorders, dermatologists should consider GLP-1RAs as adjunctive therapy in patients with co-morbid metabolic conditions. Acanthosis nigricans represents an obvious dermatologic condition in which GLP-1RA could be considered, given its clear association with obesity and T2DM.¹²

While many further studies are needed to better elucidate the role of GLP-1RAs and related pipeline medications in skin disorders, dermatologists should be resolved stay up to date with developing literature and consider their use as adjunct therapy in management of inflammatory skin disorders. 

1. Camilleri M, Acosta A. Newer pharmacological interventions directed at gut hormones for obesity. Br J Pharmacol. 2024;181(8):1153-1164. doi: https://doi.org/10.1111/bph.16278

2. Rybelsus (semaglutide) [package insert]. Novo Nordisk Inc; 2024.

3. Kawai T, Sun B, Yoshino H, et al. Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist. Proc Natl Acad Sci U S A. 2020;117(47):29959-29967. doi: https://doi.org/10.1073/pnas.2014879117

4. Saxena AR, Frias JP, Brown LS, et al. Efficacy and safety of oral small molecule glucagon-like peptide 1 receptor agonist danuglipron for glycemic control among patients with type 2 diabetes: a randomized clinical trial. JAMA Netw Open. 2023;6(5):e2314493. doi: https://doi.org/10.1001/jamanetworkopen.2023.14493

5. Pfizer Inc. Pfizer provides update on oral GLP-1 receptor agonist danuglipron. Published April 14, 2025. Accessed September 13, 2025. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-provides-update-oral-glp-1-receptor-agonist

6. ClinicalTrials.gov. Accessed September 13, 2025. https://clinicaltrials.gov/search?intr=Oral%20GLP-1

7. Eli Lilly and Company. Lilly’s oral GLP-1, orforglipron, is successful in third Phase 3 trial. Published August 26, 2025. Accessed September 13, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-oral-glp-1-orforglipron-successful-third-phase-3-trial

8. Zebound (tirzepatide) [package insert]. Eli Lilly and Company; 2022.

9. Mounjaro (tirzepatide) [package insert]. Eli Lilly and Company; 2022.

10. Camilleri M, Acosta A. Newer pharmacological interventions directed at gut hormones for obesity. Br J Pharmacol. 2024;181(8):1153-1164. doi: https://doi.org/10.1111/bph.16278

11. Jia Y, Liu Y, Feng L, Sun S, Sun G. Role of glucagon and its receptor in the pathogenesis of diabetes. Front Endocrinol (Lausanne). 2022;13:928016. doi: https://doi.org/10.3389/fendo.2022.928016

12. Lal K, Herringshaw E. The use of GLP-1 agonists in the management of cutaneous disease. J Clin Aesthet Dermatol. 2024;17(9):34-37.

13. 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. Published online April 29, 2025. doi: https://doi.org/10.1111/jdv.20694

14. Lin L, Xu X, Yu Y, et al. Glucagon-like peptide-1 receptor agonist liraglutide therapy for psoriasis patients with type 2 diabetes: a randomized-controlled trial. J Dermatolog Treat. 2022;33(3):1428-1434. doi: https://doi.org/10.1080/09546634.2020.1826392

15. Petković-Dabić J, Binić I, Carić B, et al. Effects of semaglutide treatment on psoriatic lesions in obese patients with type 2 diabetes mellitus: an open-label, randomized clinical trial. Biomolecules. 2025;15(1):46. doi: https://doi.org/10.3390/biom15010046

16. Krajewski PK, Złotowska A, Szepietowski JC. The therapeutic potential of GLP-1 receptor agonists in the management of hidradenitis suppurativa: a systematic review of anti-inflammatory and metabolic effects. J Clin Med. 2024;13(21):6292. doi: https://doi.org/10.3390/jcm13216292

17. Kawai T, Autieri MV, Scalia R. Adipose tissue inflammation and metabolic dysfunction in obesity. Am J Physiol Cell Physiol. 2021;320(3):C375-C391. doi: https://doi.org/10.1152/ajpcell.00379.2020

18. Romero-Talamás H, Aminian A, Corcelles R, Fernandez AP, Schauer PR, Brethauer S. Psoriasis improvement after bariatric surgery. Surg Obes Relat Dis. 2014;10(6):1155-1159. doi: https://doi.org/10.1016/j.soard.2014.03.025

19. Shan J, Zhang J. Impact of obesity on the efficacy of different biologic agents in inflammatory diseases: a systematic review and meta-analysis. Joint Bone Spine. 2019;86(2):173-183. doi: https://doi.org/10.1016/j.jbspin.2018.03.007

20. Clark L, Lebwohl M. The effect of weight on the efficacy of biologic therapy in patients with psoriasis. J Am Acad Dermatol. 2008;58(3):443-446. doi: https://doi.org/10.1016/j.jaad.2007.11.011

21. Pirro F, Caldarola G, Chiricozzi A, et al. Impact of body mass index on the efficacy of biological therapies in patients with psoriasis: a real-world study. Clin Drug Investig. 2021;41(10):917-925. doi: https://doi.org/10.1007/s40261-021-01080-z

COREY L. SNYDER, MD

• Dermatology resident Dell Medical School
• The University of Texas at Austin

Austin, TX

YOUSSEF ABDULLAH, MD, MBA

• Resident physician, Dell Medical School
• Co-founder, Le Chateau

Austin, TX

OLAYEMI OLUBOWALE, MD, MA Obesity medicine fellow

• Massachusetts General Hospital

Boston, MA

TED LAIN, MD

• Austin Institute for Clinical Research 

Austin, TX