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Head-to-Head Comparison: Key Metrics Semaglutide: MW 4113.58 Da | Selective GLP-1 RA | Injectable (weekly) or oral (daily with SNAC) | Mean weight loss 14.9% (STEP 1) | FDA-approved 2021 (obesity) Tirzepatide: MW ~4813.45 Da | Dual GLP-1/GIP | Injectable (weekly) | Mean weight loss 22.5% (SURMOUNT-1) | FDA-approved 2023 (obesity) Retatrutide: MW ~4500 Da | Triple GLP-1/GIP/Glucagon | Injectable (weekly) | Mean weight loss 28.7% (TRIUMPH-4 Phase 3) | Phase 3 as of 2026 Orforglipron: MW 541.65 Da | Selective GLP-1 (non-peptide) | Oral (daily, no food restriction) | Mean weight loss ~14.7% (Phase 3) | FDA-approved April 2026 Receptor Selectivity and Mechanism Differences The four compounds represent a spectrum from single-target to multi-target pharmacology