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Key Highlights Orforglipron (Eli Lilly) * 13.6% weight loss in Phase 2 * 2.1% HbA1c reduction * Highest efficacy among the three molecules in Phase 2 * Subsequently confirmed efficacy in Phase 3 with up to 14.7% weight loss * First and only FDA-approved oral small-molecule GLP-1 receptor agonist (Foundayo) Elecoglipron (AstraZeneca) * 11.8% weight loss * 1.9% HbA1c reduction * Strong Phase 2b results * Currently advancing into a global Phase 3 program Aleniglipron (Structure Therapeutics) * 12.1% weight loss * 1.5% HbA1c reduction * Encouraging efficacy with ongoing Phase 3 development Phase 2 Efficacy Comparison Weight Loss * Orforglipron: 13.6% * Aleniglipron: 12.1% * Elecoglipron: 11.8% HbA1c Reduction * Orforglipron: 2.1% * Elecoglipron: 1.9% * Aleniglipron: 1.5% As Structure Therapeutics expanded their testing into the ACCESS II trial and evaluated higher doses (specifically escalation protocols reaching 180 mg and 240 mg), the efficacy numbers jumped significantly

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Traumatic brain injury (TBI)

The tight negative feedback control that glutathione exerts on the first of two enzymes responsible for glutathione synthesis, GCL, can explain this phenomenon

Current studies suggest that peripherally administered GLP-1RA has low concentrations in the cerebrospinal fluid, and higher doses or improved delivery systems (e.g., nanoparticles, liposome encapsulation) may be needed to increase brain exposure