Research Comparison
Semaglutide vs Retatrutide: GLP-1 vs Triple Agonist Comparison
Semaglutide and retatrutide represent different generations of incretin-based peptides. Semaglutide targets the GLP-1 receptor exclusively, while retatrutide engages three receptors: GLP-1, GIP, and glucagon. Published clinical trial data from STEP and phase 2 programs provide quantitative comparisons.
Receptor Targets
Semaglutide is a selective GLP-1 receptor agonist with a 31-amino-acid sequence based on GLP-1(7-37). It includes an Aib substitution at position 8 and a C-18 fatty diacid linker at position 26 for albumin binding.
Retatrutide is a triple agonist targeting GLP-1, GIP, and glucagon receptors simultaneously. At 39 amino acids, it is the first peptide to engage all three incretin and glucagon pathways. The glucagon component adds thermogenic and lipolytic signaling not present in GLP-1-only compounds.
Published Clinical Data
Semaglutide STEP 1 (Wilding et al. 2021, PMID: 33567185): −14.9% mean weight change vs −2.4% placebo at 68 weeks, n=1961.
Retatrutide Phase 2 (Jastreboff et al. 2023, PMID: 37366315): −24.2% at highest dose (12mg) at 48 weeks. Rosenstock et al. (2023, PMID: 37385280) reported HbA1c reductions in the T2D cohort.
Frequently Asked Questions
What is the difference between semaglutide and retatrutide?+
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