An Open-Label, Single-Center Proof of Concept Study Evaluating the Efficacy and Safety of Tirzepatide for Moderate to Severe Hidradenitis Suppurativa

December 2025 | Volume 24 | Issue 12 | 1246 | Copyright © December 2025


Published online November 25, 2025

Ana Sofia Acosta-Madiedo MDa, Marcela Gutierrez CRCb, Martha Gutierrez CCRCb, Alan Villacampa PharmDc, Francisco Kerdel Bsc MBBSb

aLarkin Community Hospital, Palm Springs, FL
bFlorida Academic Dermatology Center Res & Edu, Coral Gables, FL
cEli Lilly and Company, Indianapolis, IN

Abstract
Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with obesity and metabolic dysregulation. Current therapies yield variable benefits and do not target metabolic drivers. Tirzepatide, a dual GLP-1/GIP receptor agonist, induces weight loss and exerts anti-inflammatory effects, offering a potential novel approach for the treatment of HS.
Objectives: To evaluate the efficacy and safety of tirzepatide in adults with moderate-to-severe HS.
Methods: In this open-label, single-center, single-arm proof-of-concept study, 20 adults with moderate-to-severe HS (Physician's Global Assessment greater than or equal to 3; BMI greater than or equal to 27) received once-weekly tirzepatide, titrated to maximum tolerated dose, for 24 weeks, followed by an 8-week washout. The primary endpoint was Hidradenitis Suppurativa Clinical Response (HiSCR) at week 24. Secondary endpoints included changes in PGA, Dermatology Life Quality Index (DLQI), pain visual analog scale (VAS), and Hospital Anxiety and Depression Scale (HADS). Analyses were conducted using an intention-to-treat approach.
Results: At week 24, 16 of 20 participants (80.0%; P<0.00001) achieved HiSCR. Improvements were also observed in DLQI, VAS, and PGA scores, with some benefits persisting through week 32. Treatment was well tolerated, with high adherence and favorable metabolic effects.
Limitations: Single-center, open-label design, modest sample size.
Conclusions: Tirzepatide demonstrated promising efficacy and tolerability in patients with moderate-to-severe HS and obesity. Larger randomized trials are warranted to confirm efficacy, durability, and safety.

 

INTRODUCTION

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder of the pilosebaceous unit, characterized by deep, tender, purulent cystic lesions found primarily in intertriginous areas. HS is tightly related to obesity, dyslipidemia, and type 2 diabetes mellitus (T2DM) due to its chronic state of inflammation. Adipose tissue secretes adipokines, like leptin, resistin, and visfatin, which are highly active molecules, both metabolically and immunologically. There is also suppression of adiponectin, which is anti-inflammatory.1,2 Current therapies for HS, including adalimumab, secukinumab, bimekizumab, oral and topical antibiotics, and anti-inflammatory agents, fail to address one of the root causes, the metabolic and inflammatory burden, which could be an important driver of the disease.

Glucagon-like-peptide-1 receptor agonists (GLP-1 Ra) are synthetic polypeptides that mimic the endogenous activity of glucagon-like-peptide-1 (GLP-1). Semaglutide, dulaglutide, and liraglutide are GLP-1 Ra approved for both obesity and diabetes mellitus. Tirzepatide, however, the newer generation GLP-1 Ra, has dual activity, stimulating both GLP-1 and GIP, making it even more efficacious. They have a long duration of action and effectively lower blood glucose, body weight, and body fat percentage, amongst other effects, making them now one of the front-line therapies for T2DM, dyslipidemia, and obesity. GLP-1 receptor agonists foster an anti-inflammatory state by reducing adipose tissue, body weight, and pro-inflammatory adipokines.
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