Quick Comparison
| Adapalene | Azelaic Acid | |
|---|---|---|
| Typical Concentration | OTC: 0.1% gel, apply pea-sized amount once nightly to clean, dry skin. Prescription: 0.3% gel for more resistant acne. Can be applied to slightly damp skin with less irritation than tretinoin. Results visible at 8-12 weeks. | OTC: 10% (The Ordinary). Prescription: 15% gel (Finacea for rosacea), 20% cream (Azelex for acne). Apply twice daily. Well-tolerated but may sting/itch initially. Full effects at 8-12 weeks. |
| Application | Topical (gel, cream, lotion). More stable than tretinoin — can tolerate some benzoyl peroxide layering (Epiduo combines both). | Topical (gel, cream, serum). Slightly gritty texture in some formulations. Apply to clean skin. |
| Research Papers | 8 papers | 9 papers |
| Categories |
Mechanism of Action
Adapalene
Adapalene selectively binds RAR-beta and RAR-gamma (minimal RAR-alpha affinity), reducing inflammatory signaling compared to pan-RAR agonists. It normalizes follicular epithelial differentiation and reduces corneocyte cohesion in the pilosebaceous unit, preventing microcomedo formation. Adapalene inhibits AP-1 transcription factor (c-Fos/c-Jun dimerization), suppressing IL-6, TNF-alpha, and neutrophil chemotaxis. It promotes comedolysis by accelerating desquamation of existing comedones. For anti-aging, it stimulates fibroblast collagen I and III via RAR-beta/gamma, with comparable efficacy to tretinoin. Its lipophilic naphthoic acid structure confers superior follicular penetration and light stability.
Azelaic Acid
Azelaic acid exhibits multi-modal activity: (1) Tyrosinase inhibition—competitively inhibits tyrosinase selectively in hyperactive melanocytes (melasma, PIH) while sparing normal ones; may involve mitochondrial enzyme interference in dysregulated melanocytes. (2) Antimicrobial—bacteriostatic against Cutibacterium acnes by inhibiting bacterial protein synthesis. (3) Comedolytic—normalizes follicular keratinization, reducing hyperkeratinization and corneocyte cohesion; may modulate keratinocyte differentiation. (4) Anti-inflammatory—scavenges ROS, inhibits neutrophil free radicals, reduces pro-inflammatory cytokines. Inhibits 5-alpha-reductase in sebocytes, potentially reducing sebum. Multi-pathway activity explains efficacy in acne, rosacea, and hyperpigmentation. Safe during pregnancy.
Risks & Safety
Adapalene
Common
Dryness, peeling, redness — generally less than tretinoin. Initial purging for 4-6 weeks.
Serious
Avoid in pregnancy (retinoid class).
Rare
Allergic contact dermatitis, severe peeling.
Azelaic Acid
Common
Stinging, burning, itching on initial application (usually subsides within 2 weeks). Mild dryness.
Serious
None. Safe during pregnancy and breastfeeding.
Rare
Allergic contact dermatitis, hypopigmentation (rare at cosmetic concentrations).
Full Profiles
Adapalene →
A third-generation synthetic retinoid originally developed for acne that has significant anti-aging benefits. Adapalene is more stable than tretinoin (resistant to light and oxygen degradation) and better tolerated because it selectively binds to RAR-beta and RAR-gamma receptors rather than all three subtypes. The 0.1% concentration became available OTC in 2016 (Differin), making it the most accessible prescription-strength retinoid.
Azelaic Acid →
A dicarboxylic acid naturally produced by yeast on the skin. Azelaic acid is a true multi-tasker that treats acne, rosacea, and hyperpigmentation simultaneously. It is one of the few active ingredients considered safe during pregnancy, and it uniquely targets only abnormal melanocytes — meaning it brightens dark spots without lightening normal skin. Effective for both inflammatory acne and post-inflammatory hyperpigmentation (PIH).