Peptides for acne and rosacea: from LL-37 to omiganan

The skin's own antimicrobial peptides

Skin defends itself chemically as well as physically. Its cells and sweat contain antimicrobial peptides, short molecules that kill bacteria, fungi and viruses and signal to the immune system. Two matter here. LL-37, the only human cathelicidin, is made by skin cells and immune cells ¹. Dermcidin is made only by sweat glands and secreted onto the skin surface, where a processed form shows broad antimicrobial activity (human study) ².

These peptides help explain both acne and rosacea, but in opposite ways: in acne, there may be too little of the right defence; in rosacea, too much of the wrong kind.

Rosacea: when LL-37 drives inflammation

A key 2007 study found that people with rosacea had abnormally high cathelicidin in their facial skin, processed into different peptide fragments than in healthy skin because of excess activity of a skin enzyme, kallikrein 5; injecting those rosacea-type fragments into mouse skin increased inflammation, and mice lacking the gene confirmed its role (human tissue and animal study) ³. A 2011 review describes rosacea as a disorder of innate immunity, an explanation that ties together its many triggers and the benefits of existing treatments (review) ⁴.

That understanding changed how some existing treatments are explained. In a 16-week open-label study of 15% azelaic acid gel, an approved rosacea treatment, patients showed reduced cathelicidin and kallikrein 5 gene expression in their skin, and azelaic acid directly inhibited the enzyme in cultured skin cells (open-label study and laboratory work) ⁵. In rosacea, then, the goal is to calm the cathelicidin system, not add more. Applying LL-37 to rosacea skin would run against everything this research shows; our LL-37 guide covers the peptide in detail.

Omiganan: the antimicrobial peptide that reached phase 3

Omiganan is a synthetic antimicrobial peptide modelled on indolicidin, a peptide from cattle immune cells, and was once described as the most advanced antimicrobial peptide in clinical development (review) ⁶. It was first developed to prevent catheter infections; those trials missed their primary endpoints, and a later analysis suggested skin proteases may have degraded it (laboratory study) ⁷. Laboratory work also showed it can boost interferon responses in immune cells, as LL-37 does (laboratory study) ⁸.

Its developers then turned to rosacea. According to the trial protocol, a first phase 2 study in 240 adults with papulopustular rosacea found a significant reduction in inflammatory lesions at one strength, while another strength caused more scaling and peeling than vehicle; a second phase 2 study explored doses further ⁹. The company's research summaries also cited reductions in inflammatory acne lesions in two phase 2 acne trials ¹⁰. Two phase 3 rosacea trials followed, each applying a once-daily gel or vehicle for 12 weeks in adults with papulopustular rosacea and at least 30 inflammatory facial lesions, with results posted on ClinicalTrials.gov ^{11 12}:

In the first, 263 people with severe papulopustular rosacea improved by almost exactly as much on vehicle gel as on omiganan ¹¹. In the second, with 463 people, omiganan reduced lesions and improved overall severity modestly but significantly more than vehicle ¹². The vehicle groups improved substantially in both trials, a reminder of how much rosacea fluctuates and how much a bland gel alone can help. One failed and one modestly positive phase 3 trial is usually not enough for approval, and omiganan is not approved by FDA or the European Medicines Agency ¹.

Acne: dermcidin and the defence that may be missing

Acne involves a skin bacterium, Cutibacterium acnes, along with oil, clogged pores and inflammation. A 2015 study found that recombinant dermcidin killed bacteria in the laboratory and that its expression in sweat was reduced in patients with acne (human study) ¹³. Similar reductions in sweat dermcidin had been linked to infections in atopic dermatitis (human study) ¹⁴. These findings suggest that a shortfall in natural antimicrobial peptides may contribute to some skin conditions, but they have not produced a treatment: no dermcidin product has been tested as an acne therapy. Not every study fits the pattern either; in people with recurrent staphylococcal skin infections, sweat dermcidin was not impaired (human study) ¹⁵.

A 2017 review of anti-acne drugs in early clinical trials noted the need for new agents because of antibiotic resistance and the side effects of current options, and listed mostly non-peptide candidates (review) ¹⁶. As of October 3, 2026, no antimicrobial peptide is an approved acne treatment ¹.

Omiganan in other skin conditions

Omiganan's later trials in other conditions were mixed. In 80 people with mild to moderate atopic dermatitis, it reduced Staphylococcus abundance and increased microbial diversity on the skin but, as the trial's own title states, did not improve clinical symptoms (randomised trial) ¹⁷. In facial seborrhoeic dermatitis, it was safe but did not improve the condition against placebo, while ketoconazole did (randomised trial) ¹⁸. A pattern emerges: antimicrobial peptides can change the skin's microbes without reliably improving the disease.

Why antimicrobial peptides struggle as skin drugs

Antimicrobial peptides look ideal on paper: they kill a broad range of microbes, including antibiotic-resistant strains, in the laboratory ⁶. Turning that into clinical benefit has proved difficult for three recurring reasons. First, skin is full of enzymes that break peptides down; the analysis of omiganan's failed catheter programme proposed that skin proteases degraded it, and tested a mirror-image, all-D version designed to resist them (laboratory study) ⁷. Second, killing microbes is not the same as treating a disease: in atopic dermatitis omiganan changed the skin's bacteria without improving symptoms ¹⁷. Third, the immune effects of these peptides cut both ways, as rosacea shows ³.

Pexiganan, another antimicrobial peptide, illustrates the same pattern. In two phase 3 trials in 835 patients with mildly infected diabetic foot ulcers, compared with an oral antibiotic, one trial failed to show equivalence while the other and the combined data showed similar clinical improvement (randomised trials) ¹⁹. It was not approved ¹. Two of the most advanced antimicrobial peptides, then, each ended with one failed and one partly successful pivotal trial.

Where research is heading

The lessons point to different approaches rather than more of the same. Protease-resistant designs such as the all-D omiganan ⁷, and treatments that calm the cathelicidin system in rosacea rather than add to it ⁵, are more consistent with what the trials and laboratory work have shown. None of these has reached approval for acne or rosacea as of October 3, 2026.

What is actually in peptide skincare

Most 'peptide' serums and creams contain signalling peptides, such as palmitoyl pentapeptide-4 or acetyl hexapeptide-8, marketed for wrinkles and firmness, not antimicrobial peptides designed to treat acne or rosacea. Our skin and hair hub grades each common cosmetic peptide, and our serum label decoder explains the ingredient names. If a product claims to treat acne or rosacea, that is a medicinal claim; approved treatments for both conditions exist and are prescribed by dermatologists.

Injectable peptides for skin

Some online sellers promote injected peptides for clear skin or rosacea. There is no trial support for that. Injecting LL-37 in particular carries the immunogenicity and tumour-promotion concerns FDA has raised ²⁰, and in rosacea it would add more of the peptide already driving inflammation ³.

Questions to ask a dermatologist

• Is this acne, rosacea or something else, such as seborrhoeic or perioral dermatitis?
• Which approved treatments suit my type and severity?
• Could a product's claim to treat my condition be a medicinal claim it cannot back up?
• Would any peptide product interact with my current treatment?

The bottom line

Antimicrobial peptides are part of the skin's own defence, and they help explain rosacea, where LL-37 is overproduced and inflammatory, and perhaps acne, where sweat dermcidin is reduced. But turning them into treatments has not worked well: omiganan, the most advanced, failed one phase 3 rosacea trial, succeeded modestly in another and was never approved. No antimicrobial peptide is approved for acne or rosacea, and most peptide skincare contains different peptides altogether.

Frequently asked questions

Are there peptides that treat acne?

No antimicrobial peptide is approved for acne as of October 3, 2026. Research links lower sweat dermcidin to acne, but no dermcidin treatment exists.

Does LL-37 help rosacea?

No. In rosacea, the skin already overproduces cathelicidin and processes it into inflammatory LL-37 fragments; effective treatments aim to calm that system.

What happened to omiganan for rosacea?

It had two phase 3 trials: one, in 263 people, did no better than vehicle; the other, in 463 people, showed a modest benefit. It was not approved.

Do peptide serums help acne?

Most peptide serums contain cosmetic signalling peptides marketed for wrinkles, not antimicrobial peptides, and are not acne treatments.

Why does azelaic acid work for rosacea?

One explanation, from an open-label study, is that it lowers cathelicidin and kallikrein 5 activity in rosacea skin.

Related on Grey Peptides

• Omiganan
• LL-37 guide
• Skin and hair hub

Sources

1. Grey Peptides encyclopedia entries for LL-37, omiganan (no Drugs@FDA application; no EMA authorisation) and dermcidin. Read October 3, 2026.
2. Schittek, B., et al. (2001). Dermcidin: a novel human antibiotic peptide secreted by sweat glands. Nat Immunol, 2(12), 1133-7. PMID: 11694882
3. Yamasaki, K., et al. (2007). Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med, 13(8), 975-80. PMID: 17676051
4. Yamasaki, K., et al. (2011). Rosacea as a disease of cathelicidins and skin innate immunity. J Investig Dermatol Symp Proc, 15(1), 12-5. PMID: 22076322
5. Coda, A. B., et al. (2013). Cathelicidin, kallikrein 5, and serine protease activity is inhibited during treatment of rosacea with azelaic acid 15% gel. J Am Acad Dermatol, 69(4), 570-7. PMID: 23871720
6. Melo, M. N., et al. (2006). Omiganan pentahydrochloride in the front line of clinical applications of antimicrobial peptides. Recent Pat Antiinfect Drug Discov, 1(2), 201-7. PMID: 18221145
7. Ng, S. M. S., et al. (2017). Preliminary investigations into developing all-D Omiganan for treating Mupirocin-resistant MRSA skin infections. Chem Biol Drug Des, 90(6), 1155-1160. PMID: 28581672
8. Grievink, H. W., et al. (2020). Antimicrobial Peptide Omiganan Enhances Interferon Responses to Endosomal Toll-Like Receptor Ligands in Human Peripheral Blood Mononuclear Cells. Clin Transl Sci, 13(5), 891-895. PMID: 32314872
9. Cutanea Life Sciences. Protocol CLS001-CO-PR-004/005, section 5.2 (prior phase 2 rosacea studies), as posted on ClinicalTrials.gov. Read October 3, 2026. Source
10. NHS Health Research Authority. Research summary, study reference CLS001-CO-PR-005 (cites reductions in inflammatory acne lesions with omiganan in two phase 2 trials). Read October 3, 2026.
11. ClinicalTrials.gov NCT02576860: phase 3 omiganan topical gel vs vehicle in papulopustular rosacea; 263 enrolled; completed September 5, 2017; posted results. Read October 3, 2026. Source
12. ClinicalTrials.gov NCT02547441: phase 3 omiganan topical gel vs vehicle in papulopustular rosacea; 463 enrolled; completed April 13, 2018; posted results. Read October 3, 2026. Source
13. Nakano, T., et al. (2015). Reduced expression of dermcidin, a peptide active against propionibacterium acnes, in sweat of patients with acne vulgaris. Acta Derm Venereol, 95(7), 783-6. PMID: 25673161
14. Rieg, S., et al. (2005). Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo. J Immunol, 174(12), 8003-10. PMID: 15944307
15. Rieg, S., et al. (2014). Expression of the sweat-derived innate defence antimicrobial peptide dermcidin is not impaired in Staphylococcus aureus colonization or recurrent skin infections. Clin Exp Dermatol, 39(2), 209-12. PMID: 23782241
16. Zouboulis, C. C., et al. (2017). Anti-acne drugs in phase 1 and 2 clinical trials. Expert Opin Investig Drugs, 26(7), 813-823. PMID: 28627277
17. Niemeyer-van der Kolk, T., et al. (2022). Topical antimicrobial peptide omiganan recovers cutaneous dysbiosis but does not improve clinical symptoms in patients with mild to moderate atopic dermatitis in a phase 2 randomized controlled trial. J Am Acad Dermatol, 86. PMID: 33010325
18. Rousel, J., et al. (2023). Treatment with the Topical Antimicrobial Peptide Omiganan in Mild-to-Moderate Facial Seborrheic Dermatitis versus Ketoconazole and Placebo: Results of a Randomized Controlled Proof-of-Concept Trial. Int J Mol Sci, 24(18). PMID: 37762625
19. Lipsky, B. A., et al. (2008). Topical versus systemic antimicrobial therapy for treating mildly infected diabetic foot ulcers: a randomized, controlled, double-blinded, multicenter trial of pexiganan cream. Clin Infect Dis, 47(12), 1537-45. PMID: 18990064
20. U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (cathelicidin LL-37 entry). Content current as of April 22, 2026; read October 1, 2026. FDA

Educational information, not medical advice. Each dose in this guide names its source, an approved label or a published study. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose.