Acne and rosacea: treatment and what peptide research shows

What are acne and rosacea, and how many people have them?

Acne vulgaris is a disorder of the pilosebaceous unit. Its pathogenesis is multifactorial: genetic predisposition, androgens, pro-inflammatory lipids in sebocytes, toll-like receptor 2 (TLR2) activation in keratinocytes, cytokines and inflammasomes, and most of these factors converge on mTORC1 activation⁵. It is estimated to affect 9.4% of the world population and to be the eighth most prevalent disease; it is most common in post-pubertal teens, and boys most often have the severe forms¹.

Rosacea is a chronic inflammatory disease of facial skin. A meta-analysis of 32 studies (41 populations, 26.5 million people) estimated a pooled prevalence of 5.46% in the general adult population, 5.41% in women and 3.90% in men, mostly at ages 45–60; symptom questionnaires gave higher figures than clinical diagnosis or ICD-coded registries². A further review notes that its pathogenesis combines genetic, environmental, immune, microbial and neurovascular factors¹⁵.

Symptoms and how they are diagnosed

Diagnosis of both diseases is clinical. In acne, clinicians look for comedones, papules, pustules and nodules on the face, chest and back, and severity is graded with scales such as the Investigator's Global Assessment (IGA) used in trials⁷. In rosacea, the ROSCO consensus and the 2017 National Rosacea Society Expert Committee classification moved from "subtypes" to phenotypes: persistent centrofacial erythema and phymatous changes are enough for the diagnosis; flushing episodes, papules and pustules, telangiectasia and ocular manifestations are additional features that are treated individually³⁴. Erythema, papules, pustules, telangiectasia and ocular involvement are the described manifestations¹⁵.

Standard acne treatment today

The 2024 American Academy of Dermatology (AAD) guideline presents 18 evidence-based recommendations and 5 good practice statements. It makes strong recommendations for benzoyl peroxide, topical retinoids, topical antibiotics and oral doxycycline; oral isotretinoin is strongly recommended for acne that is severe, causes psychosocial burden or scarring, or fails standard oral or topical therapy. Conditional recommendations include topical clascoterone, salicylic acid, azelaic acid, minocycline, sarecycline, combined oral contraceptives and spironolactone. As good practice, it advises combining topical treatments with different mechanisms and limiting systemic antibiotics⁶. Bacterial resistance is the reason for that caution¹⁰.

Two data points illustrate the newer drugs. In two phase 3 trials with 1440 patients, clascoterone 1% cream (a topical androgen receptor inhibitor) achieved treatment success in 18.4% and 20.3% at 12 weeks, vs 9.0% and 6.5% with vehicle⁷. In adult women, a meta-analysis of randomized trials found an odds ratio of 2.51 for treatment success with spironolactone vs placebo or doxycycline⁸. A systematic review of 15 trials concluded that low-dose or intermittent isotretinoin had efficacy comparable to high doses, with less cheilitis and xerosis⁹.

Standard rosacea treatment today

The recommended approach is by phenotype: each feature present is treated⁴. For inflammatory lesions, a phase 3 trial of 962 patients showed that ivermectin 1% cream reduced inflammatory lesions by 83.0% at 16 weeks vs 73.7% with metronidazole 0.75% (P < 0.001), with 84.9% vs 75.4% of patients "clear" or "almost clear" and better local tolerability¹¹. For persistent erythema, two randomized pivotal studies of brimonidine 0.5% gel, once daily for 4 weeks, showed greater efficacy than vehicle from 30 minutes after the first application, with no rebound or tachyphylaxis during the study period¹². Azelaic acid 15% is another studied option, with an anti-inflammatory effect described below¹³.

What peptide research has shown

No peptide is approved to treat acne or rosacea, and none appears in the AAD acne guideline⁶. What exists is a concrete scientific question — the role of one of the body's own peptides in the disease — and several early-stage candidates. They are summarized by agent.

LL-37 (cathelicidin) in the pathophysiology of rosacea. LL-37 is the human antimicrobial peptide formed when cathelicidin is processed. In a Nature Medicine study, people with rosacea had abnormally high cathelicidin levels in facial skin, and the processed forms differed from those in healthy people, owing to increased stratum corneum tryptic enzyme (kallikrein 5); in mice, injecting the rosacea peptides, adding that enzyme or deleting the inhibitor Spink5 increased inflammation, and deleting the cathelicidin gene reduced it¹⁴. A 2024 review describes how LL-37 activates TLR2, mTORC1, NF-κB and inflammasome pathways and stimulates macrophages, neutrophils, mast cells and endothelial cells¹⁵. In other words, in rosacea this peptide is part of the problem, not a treatment. Drugs already in use appear to act on this axis: in a 16-week open-label study of azelaic acid 15%, cathelicidin and kallikrein 5 messenger RNA fell in patients' skin; the authors state the study was too small to predict clinical efficacy¹³. A 2026 cell and mouse study of LL-37-induced inflammation tested injectable poly-D,L-lactic acid and reported a smaller lesion area; two authors are employed by the company LIBON Inc.¹⁷. This is preclinical evidence.

LL-37 in acne. Human sebocytes express functional cathelicidin and can kill Propionibacterium acnes (now Cutibacterium acnes) in the laboratory¹⁸. We found no trial in PubMed that gives LL-37 to people with acne or rosacea. The only clinical trial of topical LL-37 we located was in venous leg ulcers: 148 patients in a phase IIb study, with no significant improvement in the whole population and an improvement in a post hoc analysis of the subgroup with ulcers of 10 cm² or more, which the authors present as a hypothesis for a new study; it was well tolerated, and several authors were employees of the company developing the drug¹⁹. That result cannot be transferred to facial skin. For an overview of the molecule, see LL-37 and antimicrobial peptides.

Antimicrobial peptides against Cutibacterium acnes. This is the most active line. A 2026 study designed tryptophan-containing peptides derived from the skin secretions of a frog (Rana chensinensis): they showed potent antibacterial activity in minimum inhibitory concentration assays, disrupted the bacterial membrane, suppressed biofilm formation and disrupted mature biofilms; the peptide I4WL5W, with the lowest cytotoxicity, reduced bacterial load and the cytokines TNF-α, IL-6 and IL-1β in mice with acne²⁰. A 2017 review already listed antimicrobial peptides among new acne targets⁵. All of it is preclinical: cells, bacteria in culture and mice.

Topical cosmetic peptides (GHK-Cu, signal peptides). A 2026 systematic review of GHK-Cu concludes that the human clinical literature is thin and fragmented, with small trials on cosmetic facial creams, and names atrophic acne scarring as an indication needing adequate trials²¹. In our PubMed search we found no randomized trials of copper peptides in active acne or rosacea. What exists is literature on photoaged skin and wound healing, summarized in GHK-Cu: four decades of papers, few trials and Matrixyl and signal peptides; the general guide is GHK-Cu: a complete guide.

Neuropeptides (CGRP). A 2026 study found elevated serum CGRP in patients with rosacea, correlated with flushing and erythema severity, and in mice with LL-37-induced inflammation rimegepant (a small-molecule CGRP receptor antagonist) and ritlecitinib attenuated inflammation¹⁶. Here the peptide is the target, not the treatment, and the data come from the laboratory and an association study.

GLP-1 drugs (peptides approved for diabetes and obesity). A prospective, observational, single-arm study in Pakistan enrolled 120 adults with acne, hidradenitis suppurativa or increased sebaceous activity who started semaglutide; 110 completed 24 months and the acne score fell from 1.92 to 1.21, along with lower sebaceous activity and correlated metabolic improvement²². With no control group, the drug's effect cannot be separated from that of weight loss or the natural course. A 2026 review states that dermatologic evidence for these drugs comes mostly from case series and small studies, and that acne also appears among possible adverse skin reactions²³. For context, see GLP-1s beyond weight.

Safety: adverse effects and cautions

• Ivermectin vs metronidazole: the incidence of adverse events was comparable between groups¹¹.
• Brimonidine: adverse events were slightly more frequent than with vehicle, mostly dermatologic, mild and transient¹².
• Clascoterone: adverse events were few and mild; the most common was trace or mild local erythema⁷.
• Isotretinoin: mucocutaneous effects (cheilitis, xerosis) are dose-dependent⁹.
• Isotretinoin and pregnancy: it is teratogenic; the FDA describes a risk of embryo-fetal toxicity (life-threatening severe birth defects), and in the United States it is dispensed only through the iPLEDGE program, which requires avoiding pregnancy during treatment²⁵.
• Spironolactone: a 2026 retrospective study examined the risk of hyperkalemia in women with chronic kidney disease receiving it for acne²⁴.
• Systemic antibiotics: bacterial resistance in acne is a documented problem¹⁰.
• Topical LL-37 (venous ulcers): it was well tolerated and safe at two concentrations, but there are no safety data in acne or rosacea¹⁹.

Summary by agent

Frequently asked questions

Is there an approved peptide for acne or rosacea? No. The 2024 AAD acne guideline includes none, and we found no human trials of LL-37 or antimicrobial peptides in these two diseases⁶²⁰.

Why is LL-37 mentioned in rosacea if it is a protective peptide? Because in rosacea the skin has too much cathelicidin and processes it abnormally, which is associated with more inflammation; in mice, reproducing it causes inflammation and deleting the gene reduces it¹⁴. The same peptide defends the skin and can harm it when in excess.

Do copper peptides improve acne? We located no randomized trials in active acne; the 2026 GHK-Cu review names atrophic acne scars as an indication that needs trials²¹.

Does azelaic acid act on cathelicidin? In a 16-week open-label study, cathelicidin and kallikrein 5 messenger RNA decreased in rosacea patients treated with azelaic acid 15%; it was a small study, and the authors state it cannot predict clinical efficacy¹³.

Do GLP-1 drugs improve acne? An observational series of 110 patients treated with semaglutide showed a lower acne score, but it had no control group, and a review says longer randomized trials are needed²²²³.

What about antimicrobial peptides and antibiotic resistance? They are interesting because they damage the bacterial membrane and attack biofilms in the laboratory²⁰, but antibiotic resistance in acne is handled today by limiting their use and combining topical treatments⁶¹⁰.