1. What is Differin Gel?

Differin Gel is a 3rd-generation retinoid ointment containing 0.1% adapalene that reduces acne by improving clogged pores caused by keratin.1,2,3

The greatest advantage of Differin Gel is that it is less irritating. Data from five randomized trials involving a total of 900 patients comparing Differin Gel with 0.025% tretinoin gel (1st generation) showed that while the efficacy in improving acne was similar, skin irritation was reduced.4

A product photograph showing the Differin Gel 0.1% tube and packaging box arranged vertically against a white background, allowing the product name, adapalene concentration, 15g volume, and packaging type to be seen at a glance.

2. How does it work?

Acne begins when comedones clog the pores.5 Differin Gel allows keratin to shed normally inside the pores, reducing keratin buildup that clogs them.3

An illustration comparing skin cross-sections before and after treatment, showing microcomedones in pores clogged with dead skin cells being cleared by the action of Differin Gel and the pore opening up as skin cell shedding is normalized.

A clear effect on reducing sebum secretion has not been confirmed. While studies using hamster sebocytes showed a reduction in lipid synthesis and accumulation, results vary across different areas of actual human skin, making it difficult to consider Differin Gel a medication that reduces sebum secretion.6,7

3. Differences from Aklief Cream

A photograph comparing the product form and size of two topical retinoids by placing a Differin Gel 0.1% tube and an Aklief Cream 0.005% pump container side-by-side vertically on a white background.

The active ingredient in Aklief Cream, a fourth-generation retinoid ointment, is trifarotene, which selectively binds to RAR-γ, the most abundant retinoid receptor in the skin.2,8 The active ingredient in Differin Gel, a third-generation retinoid, is adapalene, which binds not only to RAR-γ but also to RAR-β, which is more abundant in non-skin tissues.2,3 Therefore, Aklief Cream is expected to have less systemic impact than Differin Gel.8

However, since the amount absorbed systemically is limited for both, the systemic impact is not what actually matters. What limits topical retinoid treatment is not systemic effects, but dermatitis.2

In this regard, Differin Gel has an edge over Aklief Cream. This is because Differin Gel 0.1% has been proven through direct comparative studies to be less irritating than 0.025% tretinoin gel (1st generation), whereas there are no studies yet proving that Aklief Cream is less irritating than 1st or 3rd generation retinoids.4,8,9

4. Precautions against dermatitis

Topical retinoids weaken the bonds between keratinocytes and also alter the lipids that fill the spaces between cells, weakening the skin barrier. When the skin barrier is weakened, the skin becomes more vulnerable to external irritation, making dermatitis more likely to occur.10,11,12

In addition, pro-inflammatory signals increase, which can cause redness, scaling, dryness, and stinging.13

Although it is less than with first-generation retinoids, with Differin Gel as well, the key is to find the minimum amount that works because of these side effects.4

An illustration showing skin barrier changes during topical retinoid use, where reduced adhesion between keratinocytes and decreased intercellular lipids make it easier for external irritants to penetrate and moisture to be lost.

5. Oral retinoids are recommended first

Clinical experience suggests that when Differin Gel is started after reducing pore blockage with oral retinoids, acne tends to be controlled with a smaller amount.

This is presumed to be because when pore blockage is reduced, Differin Gel reaches inside the pores more effectively.

You can learn more about oral retinoids on the Isotinone page.

6. How to Use

  1. Squeeze an amount of Differin Gel about the size of half a fingernail, mix it with a moisturizer, and apply a thin layer over the entire face, avoiding the eyes and mouth. The reason for mixing with a moisturizer is to start with such a small amount that it would be impossible to spread across the entire face otherwise.
  2. For the first 2 weeks, apply once every 3 days in the evening and observe your skin’s reaction.
  3. If your skin becomes red, stings, or itches after use, reduce the amount. If there is no irritation but acne is not sufficiently controlled, gradually increase the frequency to a maximum of once a day.1

An illustration showing the starting dose when mixing Differin Gel with moisturizer, with a transparent gel placed on the upper half of the index fingernail and a dotted line indicating the measurement standard.

7. Pregnancy · breastfeeding

Due to limited data on safety during pregnancy, it cannot be used if you are pregnant or planning to become pregnant. If you discover you are pregnant while using it, you must stop immediately.1

Caution is required during breastfeeding. Although it has not been confirmed that topically applied medication is transferred to the infant through breast milk, safety in such cases has not been verified. If used while breastfeeding, do not apply it to the chest and ensure the infant does not come into contact with the treated skin.1

Frequently Asked Questions

Is Differin Gel less irritating than Aklief Cream?

There are no direct comparison results between Differin Gel and Aklief Cream yet.9 However, Differin Gel has direct comparison results showing it was less irritating than 0.025% tretinoin gel,4 whereas Aklief Cream’s approval studies did not include a tretinoin control group.8 Due to this difference in evidence, Differin Gel is preferred for patients sensitive to irritation.

Is Differin Cream less irritating than the gel?

It has not been definitively proven to be less irritating. In cumulative irritation tests involving occlusive application to the back skin of healthy adults, the irritation of both formulations was similar, but this is not a basis for judging the difference when actually used on the face.14

Can acne flare up more initially?

Cases of increased lesions during the early stages of use have been rarely reported, but it is unclear if this is due to the medication. If new lesions increase, do not simply dismiss it as an adaptation process; instead, re-verify the frequency of use and the presence of dermatitis during a consultation.1

Can I apply it with a moisturizer?

Yes, you can. If your skin is sensitive, apply a thin layer of Differin Gel mixed with a moisturizer over the entire face. Applying a small amount evenly can also reduce dryness and stinging.

Is it a medication that reduces sebum?

It is not considered a medication that significantly reduces the amount of sebum in humans. While there are animal and cell studies showing inhibition of lipid synthesis in sebocytes, changes in sebum levels on the human face were small and inconsistent.6,7

Can I apply it during the day?

Differin Gel should be applied before bedtime. Since the skin may become more sensitive to sunlight during use, use sunscreen during the day.1

References

  1. Korea Pharmaceutical Information Center. Differin Gel 0.1% Drug Information.
  2. Baldwin H, Webster G, Stein Gold L, et al. 50 Years of Topical Retinoids for Acne: Evolution of Treatment. Am J Clin Dermatol. 2021;22(3):315-327. PMID: 33871811.
  3. Michel S, Jomard A, Demarchez M. Pharmacology of adapalene. Br J Dermatol. 1998;139 Suppl 52:3-7. PMID: 9990413.
  4. Cunliffe WJ, Poncet M, Loesche C, Verschoore M. A comparison of the efficacy and tolerability of adapalene 0.1% gel versus tretinoin 0.025% gel in patients with acne vulgaris: a meta-analysis of five randomized trials. Br J Dermatol. 1998;139 Suppl 52:48-56. PMID: 9990421.
  5. Thielitz A, Sidou F, Gollnick H. Control of microcomedone formation throughout a maintenance treatment with adapalene gel, 0.1%. J Eur Acad Dermatol Venereol. 2007;21(6):747-753. PMID: 17567301.
  6. Sato T, Akimoto N, Kitamura K, et al. Adapalene suppresses sebum accumulation via the inhibition of triacylglycerol biosynthesis and perilipin expression in differentiated hamster sebocytes in vitro. J Dermatol Sci. 2013;70(3):204-210. PMID: 23473858.
  7. Stinco G, Bragadin G, Trotter D, Pillon B, Patrone P. Relationship between sebostatic activity, tolerability and efficacy of three topical drugs to treat mild to moderate acne. J Eur Acad Dermatol Venereol. 2007;21(3):320-325. PMID: 17309452.
  8. U.S. National Library of Medicine. DailyMed: AKLIEF (trifarotene) cream prescribing information. Updated September 16, 2024.
  9. Thai Clinical Trials Registry. TCTR20260127006. A pilot randomized double-blinded split-face study to evaluate the efficacy of 0.005% trifarotene cream versus 0.1% adapalene gel in the treatment of mild to moderate acne vulgaris.
  10. Kim MY, Lee SE, Chang JY, et al. Retinoid Induces the Degradation of Corneodesmosomes and Downregulation of Corneodesmosomal Cadherins: Implications on the Mechanism of Retinoid-induced Desquamation. Ann Dermatol. 2011;23(4):439-447. PMID: 22148010.
  11. Li J, Li Q, Geng S. All‑trans retinoic acid alters the expression of the tight junction proteins Claudin‑1 and ‑4 and epidermal barrier function‑associated genes in the epidermis. Int J Mol Med. 2019;43(4):1789-1805. PMID: 30816426.
  12. Lee DD, Stojadinovic O, Krzyzanowska A, Vouthounis C, Blumenberg M, Tomic-Canic M. Retinoid-responsive transcriptional changes in epidermal keratinocytes. J Cell Physiol. 2009;220(2):427-439. PMID: 19388012.
  13. Kim BH, Lee YS, Kang KS. The mechanism of retinol-induced irritation and its application to anti-irritant development. Toxicol Lett. 2003;146(1):65-73. PMID: 14615068.
  14. Brand B, Gilbert R, Baker MD, et al. Cumulative irritancy potential of adapalene cream 0.1% compared with adapalene gel 0.1% and several tretinoin formulations. Cutis. 2003;72(6):455-458. PMID: 14700217.