A prospective, double-blinded, randomized head-to-head clinical trial of topical adapinoid (oleyl adapalenate) versus retinol.

Background: Retinoids, such as retinol, are widely investigated and utilized in skin care products as a treatment for photoaging but their use is limited by tolerability. Adapinoid (oleyl adapalenate, OA) is a novel third generation retinoid that is a pro-drug of adapalene, but there is little research on its effects on photoaging or its tolerability.

Objectives: The purpose of this study is to compare the effects and tolerability of OA 0.5% to retinol 0.5% cream regarding visible signs of facial photoaging including facial wrinkles, fine lines and pigmentation.

Methods: In this 12-week, double-blind, randomized clinical trial, 48 eligible participants were recruited and enroled from the Greater Sacramento region. The study consisted of a baseline and follow-up visits at weeks 4, 8 and 12. Participants were randomized to receive either topical OA 0.5% or retinol 0.5% for 12 weeks. The primary outcome was changes in the appearance of wrinkle severity at 12 weeks. Secondary outcome measures include changes in erythema, skin pigmentation, skin hydration and transepidermal water loss (TEWL).

Results: OA improved wrinkle severity by 9.45% (p < 0.0001) at week 12, whereas retinol improved wrinkle severity by 4.11% (p < 0.001) compared to baseline. When comparing the two treatment groups at week 12, the OA group improved significantly more than the retinol group (p = 0.001). OA decreased pigment intensity at week 12 by 3.88% (p < 0.0001), whereas retinol decreased pigment intensity by 3.15% (p < 0.03) compared to baseline. OA-based improvement in pigment intensity at week 12 was not significantly different from retinol (p = 0.62). OA reduced facial erythema by 13.39% (p < 0.05) at week 12, whereas the retinol group did not have a significant change. OA use led to a 14.92% decrease in TEWL by week 12 (p = 0.07), whereas the retinol group had no significant change. OA was better tolerated than retinol when assessed at all follow-up visits.

Conclusions: OA 0.5% is superior to retinol 0.5% in improving wrinkle severity and similar in improvement of pigment intensity. OA is better tolerated than retinol. Overall, the use of OA as a precursor to adapalene may be an effective method to improving the tolerability of retinoids while maintaining efficacy.

Trial registration: This study was registered on www.clinicaltrials.gov (NCT05778760).