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Once-Weekly Semaglutide 72 mg in Adults with Obesity (STEP UP)
Retatrutide vs tirzepatide vs semaglutide Category Receptor targets Retatrutide GLP-1 + GIP + Glucagon (triple) Tirzepatide GLP-1 + GIP (dual) Semaglutide GLP-1 only (single) Category Half-life Retatrutide ~6 days Tirzepatide ~5 days Semaglutide ~7 days Category Dose frequency Retatrutide Once weekly Tirzepatide Once weekly Semaglutide Once weekly Category Max studied dose Retatrutide 12 mg/week Tirzepatide 15 mg/week Semaglutide 2.4 mg/week Category Peak weight loss in trials Retatrutide -28.7% at 68 weeks (Phase 3 TRIUMPH-4) Tirzepatide -22.5% at 72 weeks (SURMOUNT-1) Semaglutide -15.8% at 68 weeks (STEP-1) Category FDA status (June 2026) Retatrutide Investigational, Phase 3 Tirzepatide Approved (obesity + T2D) Semaglutide Approved (obesity + T2D) Category Liver fat Retatrutide Up to 82% reduction (Phase 2 substudy) Tirzepatide Significant reduction Semaglutide Moderate reduction Category Unique angle Retatrutide Triple agonism may raise energy expenditure via glucagon pathway Tirzepatide Dual agonism balances effect and tolerability Semaglutide Longest clinical track record
Larsen, J., Hylleberg, B., Ng, K
Potential areas of interest include: Appetite regulation Hormonal pathways involved in satiety may influence hunger patterns
Conclusion GLP-1RAs show significant promise as a potential disease-modifying therapy for neurodegenerative and inflammatory eye diseases, acting through both systemic metabolic improvements and direct ocular mechanisms, representing a paradigm shift beyond their metabolic indications
