What is Differin?

Differin is a topical acne treatment which contains a synthetic retinoid called adapalene. Adapalene is not similar in structure to tretinoin or other retinoic acid compounds. However, like other synthetic retinoids like tazarotene, adapalene activates the same receptor targets in the skin like retinoic acid receptor (RAR) β and γ and retinoid X receptor (RXR).

Adapalene is more stable than tretinoin and can be used in conjunction with benzoyl peroxide. It is also more lipophilic, so more can accumulate within the sebaceous unit.

Differin for Acne

In a head to head comparison, 0.100% adapalene gel  was more effective than a 0.025% tretinoin gel in non-inflammatory (open and closed comedones) and inflammatory (papules and pustules) acne – it was better tolerated as well, which means less irritation.

A multi-ethnic study with Chinese, Malay, Indian, and Caucasian subjects found good tolerability among all races. A separate study on Black South Africans also found efficacy in treating acne and good tolerability.

A meta-analysis of 5 studies that compared 0.100% adapalene gel and 0.025% tretinoin gel also found them similarly effective for acne. Of particular interest, it seems adapalene begins to reduce acne after 1 week of use – which is faster than tretinoin and may be due to adapalene causing less irritation.

Another study showed that 0.1% adapalene gel was less irritating than 0.100%, 0.050%, 0.025% tretinoin and even 0.100% tretinoin microspheres (Retin-A Micro).

A study comparing 0.030% and 0.100% adapalene gel found that the 0.100% adapalene gel was significantly more effective than the 0.030% gel in treating acne.

A supplementary article submitted to Cutis reported a decrease in sebum production on subjects that were using 0.100% adapalene gel for 4 weeks. Sebum production returned to normal after the treatment was stopped. There’s a possible mechanism for adapalene to reduce sebum production by suppressing triglyceride formation in sebocytes – in hamsters.

Differin for Hyperpigmentation

Adapalene seems to also be effective for hyperpigmentation, however there is more research and evidence supporting tretinoin and tazarotene.

A non-blinded study on 65 Black African patients using a 0.100% adapalene gel found significant improvements in hyperpigmentation. Less than 5% of subjects in the study experienced skin irritation.

Studies covered in the next section on Caucasian and Chilean subjects also found brightening in overall skin pigmentation.

Differin for Anti-Ageing

In terms of treating photodamage and photoageing, there is very little research on the topic, especially compared to tretinoin and to a lesser extent tazarotene.

A Galderma study with 0.100% and 0.300% adapalene gel on 90 Caucasian subjects saw improvement in solar lentigines (freckles) and actinic keratoses. Trained dermatologists noticed an improvement in fine skin wrinkling and an overall brightening of the skin’s pigmentation. No significant change in deep wrinkles was noticed. Results were much more pronounced with the 0.3% adapalene gel.

Another Galderma study on Chilean women found similar results. They found marked improvement in skin wrinkling at 90 and 180 days of treatment using a Visia skin analyzer, though they did not differentiate between fine and deep wrinkles. Of interest is that skin thickness did not increase, which is common with tretinoin treatment, however they did find an improvement in abnormal elastin accumulation (elastosis band) in the skin.

Questions and Answers

I’ve gotten a few questions about this on my Instagram, so here they are with their answers!

pricklygoldenpear asks: Can adapalene and other retinoids be used with niacinamide? I mean like layering them. If yes, which one over or under – or are both ways OK?

As with many questions regarding ingredient compatibility and order of application – there’s very little to often no research on the topic. Almost every skin study compare one treatment vs a control treatment. Very rarely do studies look at results from one ingredient, then an additional ingredient, etc. This type of study design is significantly more complex, more time-consuming, and costly to perform.

When looking for studies that examined niacinamide and retinoids, I found none that looked at the combination of niacinamide and tretinoin or adapalene.

A study published in the JCD did compare the use of a retinyl ester (hydroxypinacolone retinoate) with niacinamide, and found an improvement in melasma, however the control cream was just a gel – so we can’t tell which ingredient in particular was responsible for the benefits.

A supplementary article submitted to the JAAD looked at a combination of niacinamide with retinaldehyde and glycolic acid and also found improvements. Again it suffers from the same problem as the previous study – which ingredient was responsible? Were the effects synergistic?

And an open-access paper comparing the combination of niacinamide, two peptides (Pal-KT and Pal-KTTKS), and retinyl propionate found it produced similar effects to 0.02% tretinoin – with less dryness and irritation.

A study published in CCID found that the combination of niacinamide, retinol, and 7-dehydrocholesterol reduced metalloproteinase and other inflammatory markers in the skin.

An in-vivo study on cultured human keratinocytes found that niacinamide could reduce some of the increased expression of aquaporin-3. This increase of aquaporin-3 is thought to increase water permeability – which could lead to skin dryness.

So while none of these studies looked niacinamide and adapalene or tretinoin directly, it seems likely that there should be no issue combining the two.

As to the “proper” ordering of the two topicals, there is no data and I don’t think it really matters. Choose the product with the lowest lipid content first, but above all else: Consistency matters more than product application order.

elspethxieI asks: Is this suitable for mothers who are breastfeeding?

From Medications’ and Mothers’ Milk by Thomas Hale, “Differin Gel (Adapalene 0.1%) is similar to Retin-A (retinoic acid or tretinoin)…Adapalene is virtually unabsorbed when applied topically to the skin. Plasma levels are almost undetectable, so milk levels would be infinitesimally low and probably undetectable.”