Azelaic acid: which other active ingredients should it be combined with?

The niacinamide is renowned for strengthening the skin barrier by stimulating ceramide synthesis and thereby limiting water loss. It also reduces redness, diminishes post-inflammatory hyperpigmentation and may modulate sebum production. Well tolerated, it is particularly suited to sensitive skin or skin prone to chronic inflammation. Combining niacinamide with azelaic acid thus appears relevant for reactive or rosacea-prone skin.

Whileazelaic acid inhibits neutrophil metabolic function, thereby limiting the release of pro-inflammatory reactive oxygen species, niacinamide enhances cutaneous tolerance and soothes the skin. This combination may also improve complexion uniformity by targeting both post-inflammatory hyperpigmentation and diffuse redness—effects that would be valuable to confirm through clinical studies.

The vitamin C is recognised for its antioxidant properties, its role in collagen synthesis and its complexion-unifying effect. It neutralises the free radicals induced by UV exposure or pollution and inhibits the activity of tyrosinase, an enzyme involved in melanin synthesis. Its combination with azelaic acid could be particularly interesting for skin prone to pigmentary spots and residual post-inflammatory redness.

A study conducted among 20 volunteers evaluated the effect of eight weekly sessions combining a 20% azelaic acid and 30% phytic acid treatment across the entire face, with the addition of 40% L-ascorbic acid on the left side only. After two months, the results showed a significant improvement in erythema and hyperpigmentation, particularly pronounced with the combination of all three actives.

An increase in skin hydration was also observed, and participants reported improvements in firmness, elasticity, uniformity of complexion, as well as reductions in redness and wrinkles. This combination therefore appears effective in enhancing the overall appearance of the skin.

The retinoids constitute a reference class of actives in dermatology for managing acne and skin ageing. Their mechanism of action is based on regulating cell turnover, increasing collagen synthesis, reducing inflammation and, for oral formulations, decreasing sebaceous gland activity. Their combination with azelaic acid could optimise the management of acne-prone and inflammatory skin.

This combination nevertheless requires precautions for sensitive skin. The retinoids, notably retinol and tretinoin, can cause irritation, dryness and flaking. Their layering with azelaic acid, known for its mattifying properties, could further compromise the skin barrier. It is therefore recommended to introduce these two actives gradually into one’s skincare routine.

When treating with oral isotretinoin, the concurrent use of topical azelaic acid is generally discouraged, as the skin is already highly sensitised by systemic exposure.

Thesalicylic acid is a lipophilic beta-hydroxy acid (BHA) capable of penetrating deeply into pores clogged with sebum and dead cells to break down blockages. Its antimicrobial and anti-inflammatory properties could complement those ofazelaic acid to target blemishes.

A trial conducted on 34 patients with mild to moderate acne evaluated the effect of four peeling sessions at two-week intervals. A combined solution of 20% salicylic acid (SA) and 20% azelaic acid (AA) was applied to one half of the face, while the other half received a 25% trichloroacetic acid (TCA) peel.

The results showed a faster improvement in inflammatory lesions with the AS/AA combination, and in non-inflammatory lesions with TCA. After four sessions, both treatments resulted in a comparable and significant improvement, although participants expressed a preference for the AS/AA-treated side, finding it more comfortable.

Well-known to acne-prone skin, benzoyl peroxide has keratolytic and antibacterial properties that prevent the clogging of pores by accumulated dead skin cells and eliminate Cutibacterium acnes, the bacterium involved in the inflammation of acne lesions. Its combination with azelaic acid is based on the complementarity of their actions: while benzoyl peroxide rapidly targets bacterial proliferation, azelaic acid works more gently by limiting inflammation and reducing associated redness.

It would be interesting for clinical trials to investigate this combination in order to assess its efficacy and tolerability.

Thehyaluronic acid is a glycosaminoglycan naturally present in the skin’s extracellular matrix, recognised for its ability to retain water. Depending on its molecular weight, it hydrates the superficial layers of the epidermis or penetrates more deeply to support cellular cohesion and the skin’s barrier function.

Its combination with azelaic acid is relevant for reducing blemishes and redness whilst preserving skin hydration. Indeed, theazelaic acid can sometimes slightly dehydrate the skin, particularly at higher concentrations (15–20%). Hyaluronic acid, by providing immediate hydration, offsets this effect and improves long-term tolerance.

Despite some common misconceptions, hyaluronic acid on its own is not sufficient to sustainably hydrate the skin. Without the addition of lipids, for example in a cream or balm, the water it attracts is liable to evaporate from the skin.

Thearbutin acid is a hydroquinone derivative naturally found in certain plants such as bearberry. In cosmetics, it is recognised for its depigmenting action, mainly via tyrosinase inhibition. Alpha-arbutin is particularly indicated to fade brown spots and is well tolerated by most skin types. Associating theazelaic acid with arbutin acid could enhance its depigmenting effects. It remains a hypothesis, however, as no study to date has investigated any potential synergy between these actives.

Certain individuals also question the appropriateness of combining azelaic acid with kojic acid to reduce their brown spots. However, ifkojic acid is authorised in cosmetics, it is suspected of crossing the skin barrier and being carcinogenic, mutagenic and an endocrine disruptor. For this reason, we advise against using kojic acid, with or without azelaic acid. If you havehyperpigmentation, there are other active ingredients whose safety is better documented.

For the same reasons, some individuals question the association between azelaic acid and hydroquinone. As a reminder, the hydroquinone is a highly effective yet controversial depigmenting agent: it is suspected of being carcinogenic, allergenic and reprotoxic. In Europe, only professional use is authorised. At Typology, we do not recommend using hydroquinone, alone or in combination with azelaic acid, as a precaution.

Azelaic acid can also be combined withtranexamic acid, an active known for its depigmenting properties. A study conducted in 33 women with moderate to severe hyperpigmentation assessed the daily application of a cream combining these two agents (concentrations unspecified) over six weeks. Analysis of photographs, dermatological evaluation and software assessment revealed an improvement in skin pigmentation at the end of the study.

Alpha-hydroxy acids (AHAs), such as glycolic acid and mandelic acid, exert a keratolytic action that promotes cellular renewal and improves skin texture and tone uniformity. Combining azelaic acid with these fruit acids can reinforce the management of skin prone to imperfections and pigmented spots.

A 24-week study of 60 patients with melasma showed that a 30% peel ofglycolic acid combined with a 20% azelaic acid cream led to a more marked reduction in the MASI score than treatment with azelaic acid alone. However, for sensitive skin, it is preferable to avoid their simultaneous application to limit the risk of irritation.

Regarding mandelicacid, which is milder and better tolerated than glycolic acid, no study has yet confirmed the benefit of combining it with azelaic acid, although theoretically the combination could offer an interesting synergy.

The sulphur is a time-honoured active ingredient still used in cosmetics, mainly for its mattifying, anti-inflammatory, keratolytic and antimicrobial properties, akin to those of azelaic acid. Its principal drawback is its odour, which may deter some individuals. The combination of azelaic acid and sulphur thus presents an interesting rationale. Since both exert substantially identical actions, their combination could target multiple factors in the development of blemishes, such as excess sebum, hyperkeratinisation, bacterial proliferation and inflammation.

The synergy between azelaic acid and sulphur remains hypothetical today due to a lack of clinical studies. Moreover, the sulphur, like azelaic acid, can have a slightly drying effect on the skin. Their combination, although potentially complementary, could therefore prove too irritating.

The bakuchiol is a plant-derived compound extracted from the seeds of Psoralea corylifolia, often described as a gentle alternative to retinol. It is recognised for its antioxidant and anti-inflammatory properties, as well as its ability to reduce brown spots and signs of ageing without causing skin sensitisation. Bakuchiol and azelaic acid may offer a synergistic approach to target both blemishes, excess sebum, redness and photoageing.

Azelaic acid and bakuchiol could be an interesting option for individuals seeking an active yet gentle routine, particularly in cases of mild rosacea or frequent blemishes. It would be beneficial for future research to investigate this potential synergy.

The zinc, often found in the form of zinc gluconate, zinc PCA or zinc oxide, is known for its sebum-regulating, photoprotective, antibacterial and anti-inflammatory properties. Its combination with azelaic acid could be relevant to reduce hyperseborrhoea and diminish the shine of oily or acne-prone skin, although this synergy has not yet been clinically tested in this context.

In contrast, studies have evaluated the efficacy of a treatment combining 0.075% tazarotene, 20% azelaic acid, 0.1% tacrolimus and 10% ofzinc oxide on melasma. Sixteen patients with hyperpigmentation applied this formulation daily for 20 weeks. The results showed a significant improvement in the MASI score (Melasma Area and Severity Index), falling from 18.9 to 13.3 on average, with a quarter of participants reaching a score below 8. Reported adverse effects were mainly mild and transient.

Nevertheless, it remains difficult to isolate the specific role of the azelaic acid–zinc oxide combination, as the active ingredients are combined with other components.

The gluconolactone is a polyhydroxy acid (PHA) that stands out from other exfoliants by its high skin tolerance. Thanks to its bulkier molecular structure, it slowly penetrates the skin, which significantly limits the risk of irritation. Gluconolactone is therefore the exfoliant of choice for sensitive skin. Its combination with azelaic acid may suit compromised skin exhibiting imperfections, vascular sensitivity or even rosacea flare-ups.

No clinical trial has yet validated this combination. However, their complementary mechanisms of action suggest that the association of azelaic acid and gluconolactone could be beneficial for sensitive or combination skin prone to acne or redness.

The vitamin E (tocopherol) is a lipophilic antioxidant naturally present in sebum, where it protects cellular membranes from oxidative stress by neutralising free radicals generated by UV, pollution or inflammation. By limiting the oxidation of skin lipids such as squalene, it helps prevent certain issues, particularly acne. In formulations, it also protects oxidation-sensitive actives. Thus, although azelaic acid is stable, its combination with vitamin E can be beneficial in formulations containing other oxidisable compounds.

Thetea tree essential oil is well known for its antibacterial, antifungal and anti-inflammatory properties. Diluted in a carrier oil, it is frequently used as a topical treatment to minimise imperfections. It is possible that combining it with azelaic acid could enhance its antibacterial and soothing action and help prevent acne flare-ups. However, we recommend caution before combining azelaic acid with thetea tree essential oil, this combination can be irritating to sensitive skin or at high concentrations.

Furthermore, to date no clinical trial has validated the efficacy and tolerability of combining azelaic acid with tea tree essential oil.

Urea is both a hydrating and exfoliating agent. At low concentrations (2–10%), it acts as a humectant in reinforcing the skin’s barrier function, while at higher concentrations (>10%), it exerts a keratolytic action that softens and smooths the skin. Its combination with azelaic acid may amplify exfoliation while benefiting from the latter’s anti-inflammatory properties, a combination particularly interesting for psoriasis-prone skin, an inflammatory dermatosis characterised by skin thickening.

Once again, no study to date has examined the combination of azelaic acid and urea, which warrants caution.

Rich in essential fatty acids (linoleic acid and alpha-linolenic acid), therosehip oil promotes skin regeneration, diminishes scars, pigmentation spots and fine lines, while enhancing skin elasticity. Its combination with azelaic acid could therefore target imperfections, redness and post-inflammatory marks alike.

However, this oil is known to be mildly comedogenic, and its undiluted application is not recommended for oily or acne-prone skin, although it is generally well tolerated by normal to dry skin. Nonetheless, its comedogenic potential depends on the formulation and concentration. To date, no study has demonstrated any specific benefit of combining it with azelaic acid.

• DUA R. et al. Combination of glycolic acid peel and 20 % topical azelaic acid cream in patients with melasma: efficacy and quality-of-life improvement. Journal of Cosmetic Dermatology (2016).

• SLUZEVICH J. et al. Evaluating the efficacy, safety and tolerability of the combination of tazarotene, azelaic acid, tacrolimus and zinc oxide for the treatment of melasma: a pilot study. The Journal of Clinical and Aesthetic Dermatology (2019).

• HAY R. A. et al. Clinical and dermoscopic assessment of combined (20% salicylic acid and 20% azelaic acid) versus 25% trichloroacetic acid chemical peel in acne: a randomised controlled trial. Journal of Dermatological Treatment (2019).

• PEINEMANN F. et al. Topical azelaic acid, salicylic acid, nicotinamide, sulphur, zinc and fruit acids (alpha-hydroxy acids) for acne. Cochrane Database of Systematic Reviews (2020)

• ERKIERT-POLGUJ A. et al. Clinical evaluation of anti-ageing effects of combined therapy – azelaic acid, phytic acid and vitamin C applied layer by layer in women with Fitzpatrick skin phototypes II and III. Journal of Cosmetic Dermatology (2022).

• MAYBURY C. et al. A systematic review to evaluate the efficacy of azelaic acid in the treatment of acne, rosacea, melasma and skin ageing. Journal of Cosmetic Dermatology (2023).

• Chabert L. et al. In vitro and in vivo Evaluation of a novel peeling system combining azelaic and tranexamic acids for targeted hyperpigmentation reduction. Dermatology and Therapy (2025).