Research Purposes Only

• First-in-class synthetic 39-amino acid dual GIP/GLP-1 receptor agonist ('twincretin') with imbalanced receptor binding profile and biased signaling at GLP-1R
• FDA-approved May 2022 (Mounjaro for T2D), November 2023 (Zepbound for obesity), December 2024 (Zepbound for OSA) — extensively validated in 2,000+ peer-reviewed publications
• Engineered with 2 Aib residues (DPP-4 resistance), C20 fatty diacid albumin-binding moiety (5-day half-life), enabling once-weekly dosing; cryo-EM structures elucidated for both GIPR-Gs and GLP-1R-Gs complexes

• First-in-Class Dual GIP/GLP-1 Receptor Agonist: 39aa twincretin with imbalanced dual agonism favoring GIPR, biased GLP-1R signaling (cAMP > beta-arrestin), FDA-approved Mounjaro (T2D 2022)/Zepbound (obesity 2023), 3,000+ publications
• Unprecedented Weight Loss Efficacy: SURMOUNT-1 (Jastreboff et al., 2022, NEJM): 22.5% mean body weight reduction at 72 weeks, 39.7% participants achieved ≥25% loss, SURMOUNT-5 superior to semaglutide
• Clinical Status: SURPASS-CVOT cardiovascular non-inferiority vs dulaglutide with 16% lower all-cause mortality (HR 0.84), SUMMIT trial 38% reduction CV death/worsening HF in HFpEF+obesity (HR 0.62), SYNERGY-NASH 73.3% MASH resolution at 15mg

• First-in-class synthetic 39-amino acid dual GIP/GLP-1 receptor agonist ('twincretin') with imbalanced receptor binding profile and biased signaling at GLP-1R
• FDA-approved May 2022 (Mounjaro for T2D), November 2023 (Zepbound for obesity), December 2024 (Zepbound for OSA) — extensively validated in 2,000+ peer-reviewed publications
• Engineered with 2 Aib residues (DPP-4 resistance), C20 fatty diacid albumin-binding moiety (5-day half-life), enabling once-weekly dosing; cryo-EM structures elucidated for both GIPR-Gs and GLP-1R-Gs complexes

• First-in-class synthetic 39-amino acid dual GIP/GLP-1 receptor agonist ('twincretin') with imbalanced receptor binding profile and biased signaling at GLP-1R
• FDA-approved May 2022 (Mounjaro for T2D), November 2023 (Zepbound for obesity), December 2024 (Zepbound for OSA) — extensively validated in 2,000+ peer-reviewed publications
• Engineered with 2 Aib residues (DPP-4 resistance), C20 fatty diacid albumin-binding moiety (5-day half-life), enabling once-weekly dosing; cryo-EM structures elucidated for both GIPR-Gs and GLP-1R-Gs complexes

Tesamorelin is a 44-amino acid synthetic GHRH analog with N-terminal trans-3-hexenoic acid modification conferring DPP-IV resistance and extended half-life (26-38 minutes vs. 2 minutes for native GHRH). FDA-approved (2010) as Egrifta for HIV-associated lipodystrophy. Selectively activates pituitary GHRH receptors via Gs-cAMP-PKA signaling, stimulating pulsatile GH release while preserving IGF-1 feedback regulation.

• Synthetic GHRH Analog: 44-amino acid polypeptide with N-terminal trans-3-hexenoic acid modification, enhanced DPP-IV resistance, 26-38 min half-life vs. minutes for native GHRH, 150+ publications
• Physiological GH Axis Modulation: Selective GHRH-R agonist preserving pulsatile GH secretion patterns, 15.2% VAT reduction at 26 weeks, IGF-1 feedback regulation intact, no continuous GH elevation
• Clinical Status: FDA-approved Egrifta (2010) for HIV-associated lipodystrophy, Egrifta WR (F8 formulation, March 2025) weekly reconstitution, ongoing research in neurocognitive function/hepatic fat